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Kaimen Rigor review

Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.

Durbin AP, Van Wesenbeeck L, Pierce KK, Herrera-Taracena G, Ebone L, Buelens A, Lutton P, Sabundayo BP, Van Eygen V, De Clerck K, Fetter I, Voge NV, Fang X, Goeyvaerts N, Vandendijck Y, Mayfield J, Lenz O, De Meyer S, Kakuda TN, He H, Amaro-Carambot E, Akli RD, Carmolli M, De Marez T, Whitehead SS, Van Loock M, Rasschaert F

DOI: 10.1056/NEJMoa2500179
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/b0f43c53-f8c1-41ac-81be-dcd363e38a61 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

1.25 / 5

Critical — serious problems across many checks

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingData & code availability not met−0.5★
ReportingStatistical analysis partially met−0.25★

Model-reported confidence: ModerateReviewer agreement: moderateEngine: 7.29.0Source: full text

Not verified in this report

Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
Primary efficacy endpoint is DENV-3 RNA viral load AUC, a surrogate outcome. No validated evidence linking this surrogate to clinical benefit is provided, and target engagement at the tested dose is not demonstrated.
“The primary objective was to assess the antiviral activity of mosnodenvir versus placebo in terms of reduction of DENV-3 RNA by evaluating the area under the DENV-3 RNA viral load (VL) concentration-time curves from immediately before inoculation (D1) until…”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The reported effect is reduction in viral RNA AUC, with 60% of high-dose participants having undetectable RNA vs 0% in placebo. The magnitude is not anchored to a minimal clinically important difference or clinical benefit.
“The proportion of participants without signs of DENV-3 infection was 0% (0/6), 17% (1/6), 60% (6/10) in low-, medium-, high-dose regimens, respectively, versus 0% (0/7) in the placebo arm.”
Find in source
03Data and code not shared
highDisclosurereviewer-assessedFull detail
No data availability statement, repository deposit, accession numbers, or code-sharing mechanism is reported in the manuscript.

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 103AuthenticityData authenticity concerns 204DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

lowinternal contradiction
The Race row for 'Multiple' in the Combined mosnodenvir column reports '2 (8.79.1)', a malformed percentage; the correct value is 9.1% (2/22). This is a formatting/typographical issue rather than a data integrity problem.
“Multiple | 1 (12.5) | 0 | 0 | 2 (18.2) | 2 (8.79.1) | 3 (10.0)”
Table 1Find in source
lowinternal contradiction
In Table 1, the Race 'Multiple' cell for the Combined mosnodenvir arm reads '2 (8.79.1)' which is a malformed percentage; 2/22 = 9.1%, so the printed value is internally inconsistent.
“Multiple | 1 (12.5) | 0 | 0 | 2 (18.2) | 2 (8.79.1) | 3 (10.0)”
Table 1Find in source
lowinternal contradiction
Table 1 reports the Combined mosnodenvir arm 'Multiple' race count as '2 (8.79.1)', an invalid percentage; with N=22, 2 participants would be 9.1%, not 8.79.1%.
“Multiple | 1 (12.5) | 0 | 0 | 2 (18.2) | 2 (8.79.1) | 3 (10.0)”
Table 1Find in source

Overstated conclusions

3 findings · worst high

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed
Conclusions only partially backed by the presented evidenceAssessed

12 major claims checked against the paper's own evidence: all adequately supported.

partialReviewer 2
The associated individual risks from emerging NS4B variations are minor.
The paper argues risks are minor because peak/duration of viremia and symptoms were not increased, but this is reasoning from a small sample and the long-term implications of the variants are not established by the data presented.
Evidence: Peak and duration of DENV-3 RNA comparable or lower than placebo; symptom frequency/severity not increased.
“The associated individual risks based on these limited data are considered minor as the peak and duration of the DENV-3 RNA levels were comparable or lower than those in the placebo arm.”
DiscussionFind in source
supportedReviewer 1
Mosnodenvir significantly reduced DENV-3 viral load versus placebo in a dose-dependent manner without relevant clinical safety findings in a CHIM.
The primary Tobit ANOVA result and the dose-dependent proportions of participants without detectable infection directly support the claim; safety is appropriately qualified as no apparent concerns in a small sample.
Evidence: Primary Tobit ANOVA p<0.001 for high-dose vs placebo; proportion without signs of infection 0%, 17%, 60% across dose arms vs 0% placebo; safety table showing mostly mild/moderate AEs.
“Mosnodenvir significantly reduced DENV-3 viral load versus placebo in a dose-dependent manner without relevant clinical safety findings in a CHIM.”
ConclusionFind in source
supportedReviewer 1
The proportion of participants without signs of DENV-3 infection increased with mosnodenvir dose versus placebo.
The reported proportions are internally consistent and directly demonstrate a dose-response relationship.
Evidence: Proportions 0% (0/6), 17% (1/6), 60% (6/10) vs 0% (0/7) reported in abstract and results.
“The proportion of participants without signs of DENV-3 infection was 0% (0/6), 17% (1/6), 60% (6/10) in low-, medium-, high-dose regimens, respectively, versus 0% (0/7) in the placebo arm.”
AbstractFind in source
supportedReviewer 1
Emergent NS4B amino acid variations were detected in all available mosnodenvir-treated participants with sequencing data and in none of the placebo participants.
This claim is directly supported by the reported sequencing results.
Evidence: NS4B sequencing data: emergent variations in 14/14 mosnodenvir participants with available data, 0/7 placebo.
Emergent amino acid variations in the NS4B region were detected in all 14 participants with available NS4B sequencing data in the mosnodenvir arms, while none were observed in the placebo arm.
Resultsreviewer’s wording
supportedReviewer 1
The variations that emerged under mosnodenvir dosing point to NS4B as the target for mosnodenvir.
The emergence of NS4B variants only under drug pressure, together with cited preclinical findings, supports this mechanistic interpretation.
Evidence: NS4B variants in all treated participants with sequencing; none in placebo; consistency with preclinical findings cited.
“The variations that emerged under mosnodenvir dosing were consistent with preclinical findings, pointing to NS4B as the target for mosnodenvir.”
Discussion ¶4Find in source
supportedReviewer 1
Mosnodenvir can reduce the incidence of DENV-3 infection and associated symptomatology prophylactically in a dengue-naïve population.
The presented prevention proportions and serology outcomes support the claim, with the usual CHIM-to-field extrapolation caveat stated by the authors.
Evidence: Dose-dependent prevention rates (0%, 17%, 60% vs 0% placebo); no seroconversion in participants without detectable DENV RNA.
“mosnodenvir administered in low, medium and high dose prevented DENV-3 infection (undetectable DENV RNA, no anti-DENV IgM/IgG/nAb seroconversion and no DENV-associated rash) in a dose-dependent manner, demonstrating that mosnodenvir can reduce the incidence of DENV-3 infection and associated symptomatology, prophylactically in a dengue-naïve population.”
Discussion ¶3Find in source
supportedReviewer 2
Mosnodenvir significantly reduced DENV-3 viral load versus placebo in a dose-dependent manner.
The Tobit ANOVA (p<0.001) and Wilcoxon rank sum (p=0.001) results and the dose-dependent proportion without infection (0%, 17%, 60% vs 0%) directly support this claim.
Evidence: Tobit ANOVA p<0.001 for high dose vs placebo; proportion without signs 0/6, 1/6, 6/10 vs 0/7.
“A Tobit analysis of variance showed a statistically significant reduction on log 10 AUC D1-D29 VL in mosnodenvir high-dose versus placebo participants (2-sided p<0.001).”
AbstractFind in source
supportedReviewers 2, 3
Mosnodenvir prevented DENV-3 infection in a dose-dependent manner.
The proportion of participants with no detectable DENV-3 RNA and no seroconversion increased with dose, directly supporting prevention.
Evidence: 0% (0/6), 17% (1/6), 60% (6/10) without infection in low/medium/high vs 0% (0/7) placebo.
The proportion of participants with all available DENV-3 RNA measurements being undetectable was 0% (0/6), 17% (1/6), 60% (6/10) in the low-, medium-, and high-dose arms, respectively, versus 0% (0/7) in the placebo arm.
Resultsreviewer’s wording
supportedReviewer 2
Emergent NS4B amino acid variations emerged under mosnodenvir dosing and not placebo.
Sequencing data show NS4B variations in all 14/14 mosnodenvir participants with available data and none in placebo, directly supporting the claim.
Evidence: NS4B variations detected in 14/14 mosnodenvir participants vs 0/7 placebo.
“Emergent amino acid variations in the NS4B region were detected in each of the 14 participants with available NS4B sequencing data in the mosnodenvir dose arms, while none were observed in the placebo arm.”
ResultsFind in source
supportedReviewer 2
Mosnodenvir did not have any apparent safety concerns.
The safety data (mostly mild/moderate AEs, no deaths, no serious AEs in dosed participants) support this claim, with the caveat of small sample size.
Evidence: No serious AEs among mosnodenvir-dosed participants; AEs mild/moderate and reversible.
“None of the mosnodenvir dosed participants had serious AEs, and none died. All out-of-range laboratory findings were isolated and fully reversible.”
ResultsFind in source
supportedReviewer 3
Mosnodenvir significantly reduced DENV-3 viral load versus placebo.
The primary Tobit ANOVA and exact Wilcoxon test both show a statistically significant reduction in log10 AUC D1-D29 VL for high-dose mosnodenvir versus placebo.
Evidence: Tobit ANOVA (2-sided p<0.001) and exact Wilcoxon rank sum (2-sided p=0.001) on log10 AUC D1-D29 VL.
“A Tobit analysis of variance showed a statistically significant reduction on the log 10 AUC D1-D29 VL in the high-dose mosnodenvir arm versus the placebo arm (2-sided p<0.001)”
AbstractFind in source
supportedReviewer 3
Mosnodenvir had no relevant clinical safety findings in this study.
No serious AEs or deaths occurred in mosnodenvir-dosed participants; reported AEs were mostly mild/moderate and reversible.
Evidence: Safety analysis: no SAEs in mosnodenvir arms, all AEs mild-to-moderate except two severe (one COVID-19, one lipase/glycemia increase), no deaths.
“None of the mosnodenvir dosed participants had serious AEs, and none died.”
ResultsFind in source

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

INADEQUATESurrogate endpoint
Primary efficacy endpoint is DENV-3 RNA viral load AUC, a surrogate outcome. No validated evidence linking this surrogate to clinical benefit is provided, and target engagement at the tested dose is not demonstrated.
“The primary objective was to assess the antiviral activity of mosnodenvir versus placebo in terms of reduction of DENV-3 RNA by evaluating the area under the DENV-3 RNA viral load (VL) concentration-time curves from immediately before inoculation (D1) until D29 (AUCD1-D29).”
Find in source
INADEQUATEEffect size
The reported effect is reduction in viral RNA AUC, with 60% of high-dose participants having undetectable RNA vs 0% in placebo. The magnitude is not anchored to a minimal clinically important difference or clinical benefit.
“The proportion of participants without signs of DENV-3 infection was 0% (0/6), 17% (1/6), 60% (6/10) in low-, medium-, high-dose regimens, respectively, versus 0% (0/7) in the placebo arm.”
Find in source

Data authenticity concerns

1 finding · worst low

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Methods and results do not matchAssessed

4 integrity concerns flagged (0 high).

lowmethod result mismatch
The Statistical analysis section states the primary efficacy analysis included all participants from Cohort 1 Group 1, but Results and Table 1 report an efficacy analysis set of 29 inoculated participants across all arms; this should be clarified.
“The primary efficacy analysis included all participants from Cohort 1 Group 1 who were inoculated with rDEN3Δ30.”
Table 1Find in source

Reporting gaps

2 findings · worst high

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data and code not sharedAssessed
Statistical reporting gaps (tests, assumptions, effect sizes)Assessed

Eight Dimensions6 pass · 1 warn · 1 fail

The introduction cites dengue epidemiology, the limitations of current vaccines, and mosnodenvir's mechanism (NS3-NS4B inhibition) with in vitro, mouse, and NHP efficacy data. The study objective follows logically from this premise. The discussion explicitly acknowledges CHIM limitations and the need for field confirmation, satisfying the limitations-addressed criterion.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise: dengue lacks antiviral prophylaxis/treatment, mosnodenvir has a defined mechanism and promising preclinical and first-in-human data, and a CHIM is an appropriate early-stage model.

Evidence

“Licensed dengue treatments are currently unavailable and management consists of supportive measures, such as antipyretics and volume repletion.”

Introduction ¶1Find in source

paraphrase[Introduction, paragraph 3]

“Mosnodenvir is an oral, pan-serotype dengue small-molecule antiviral, that blocks viral replication by inhibiting de novo DENV nonstructural protein 3 (NS3)-NS4B interaction.”

“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”

Discussion ¶5Find in source

PASSReviewer 2· 90% conf

The premise is well established: dengue burden, lack of antiviral treatment, vaccine limitations, and preclinical/first-in-human data on mosnodenvir are cited, with a clear rationale for a prophylactic antiviral and a stated hypothesis.

Evidence

“In contrast, an oral antiviral could be deployed in outbreaks, could limit cases in endemic areas through a prophylactic approach, and may be used for travelers and those who cannot receive a vaccine.”

Introduction ¶1Find in source

“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”

DiscussionFind in source

PASSReviewer 3· 90% conf

The premise is firmly grounded in prior literature on dengue burden, vaccine limitations, and mosnodenvir's mechanism and preclinical efficacy, with a clear rationale for prophylaxis.

Evidence

“Mosnodenvir (also known as JNJ-64281802) is an oral, pan-serotype dengue small-molecule antiviral, that blocks viral replication by inhibiting de novo DENV nonstructural protein 3 (NS3)-NS4B interaction.”

IntroductionFind in source

“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”

DiscussionFind in source

The randomized, double-blind design and unit of randomization (participant) are clear. A sample size simulation demonstrated >85% power for the primary endpoint. Inclusion/exclusion criteria are summarized and referenced to the protocol. Missing data were handled by pre-specified rules: one high-dose participant with a missing D29 sample was excluded from the primary analysis. The randomization method (e.g., block/stratified/computer-generated sequence) is not reported, so randomization_method is only partially adequate.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodINADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Randomized, double-blind, placebo-controlled CHIM with a simulated power calculation, clear inclusion/exclusion criteria, and pre-specified handling of missing data; the specific randomization algorithm is not stated.

Evidence

“In this phase 2a, double-blind study, healthy adults were randomized to receive once daily oral mosnodenvir at different dose levels or placebo for 26 days”

AbstractFind in source

“Based on these simulations, the power to detect a relevant reduction of ≥ 30% on log 10 AUC D1-D29 (VL) at the 2-sided 10% significance level was calculated to be more than 85% with 6 participants in the placebo arm and 10 participants in the mosnodenvir high-dose arm.”

MethodsFind in source

“One participant in the high-dose mosnodenvir arm had a missing sample on D29 and was excluded from the primary analysis since the missing value could not be imputed according to pre-specified statistical analysis plan rules.”

Table 1Find in source

PASSReviewer 2· 80% conf

A pre-specified sample-size calculation, inclusion/exclusion criteria, double-blinding, and handling of missing data are reported; the main gap is that the randomization method (sequence generation) is not described.

Evidence

paraphrase[Methods, Study procedures]

“Participants were randomized to receive either high-dose mosnodenvir; (N=10) or matching placebo (N=6) (Group 1) or medium- (N=6) and low-dose (N=6) mosnodenvir or matching placebo (N=2) (Group 2).”

“the power to detect a relevant reduction of ≥ 30% on log 10 AUC D1-D29 (VL) at the 2-sided 10% significance level was calculated to be more than 85%”

MethodsFind in source

PASSReviewer 3· 80% conf

Core clinical trial design elements are well reported: double-blind, placebo-controlled, with sample-size simulation, inclusion/exclusion criteria, and a pre-specified missing-data rule.

Evidence

“This is a phase 2a, randomized, double-blind, placebo-controlled human infection model (CHIM) study”

MethodsFind in source

“the power to detect a relevant reduction of ≥ 30% on log 10 AUC D1-D29 (VL) at the 2-sided 10% significance level was calculated to be more than 85% with 6 participants in the placebo arm and 10 participants in the mosnodenvir high-dose arm.”

MethodsFind in source

Table 1Find in source

Participants are described as healthy adults 18-55 years who are DENV/ZIKV seronegative, and Table 1 provides age, sex, race, ethnicity, and site. Since both sexes were enrolled, sex_justified is not applicable. Weight is not reported, making age_weight_health only partially adequate. Demographics are otherwise well characterized.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthINADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Sex, age, health status, and race/ethnicity are reported in Table 1 and text; body weight is not reported, so age/weight/health reporting is incomplete.

Evidence

“We enrolled healthy individuals 18–55 years of age, who were confirmed to be seronegative to DENV and Zika virus (ZIKV) prior to enrollment”

MethodsFind in source

“Mean age (SD), years | 30.0 (7.29) | 29.5 (4.59) | 36.0 (10.68) | 34.5 (9.08) | 33.6 (8.64) | 32.6 (8.35)”

Table 1Find in source

“Female sex, n (%) | 4 (50.0) | 4 (66.7) | 5 (83.3) | 7 (63.6) | 16 (69.6) | 20 (64.5)”

Table 1Find in source

PASSReviewer 2· 75% conf

Sex, age, health status, and demographics (race/ethnicity) are reported; weight is not reported, which is a minor omission for an adult CHIM trial.

Evidence

“Female sex, n (%) | 4 (50.0) | 4 (66.7) | 5 (83.3) | 7 (63.6) | 16 (69.6) | 20 (64.5)”

Table 1Find in source

“We enrolled healthy individuals 18–55 years of age, who were confirmed to be seronegative to DENV and Zika virus (ZIKV) prior to enrollment”

MethodsFind in source

PASSReviewer 3· 75% conf

Sex, age, health status, race, and ethnicity are reported in Table 1; weight is not reported.

Evidence

“Female sex, n (%) | 4 (50.0) | 4 (66.7) | 5 (83.3) | 7 (63.6) | 16 (69.6) | 20 (64.5)”

Table 1Find in source

“Mean age (SD), years | 30.0 (7.29) | 29.5 (4.59) | 36.0 (10.68) | 34.5 (9.08) | 33.6 (8.64) | 32.6 (8.35)”

Table 1Find in source

“We enrolled healthy individuals 18–55 years of age”

MethodsFind in source

Human subjects research: the protocol was reviewed and approved by Independent Ethics Committees at each site, written informed consent was obtained from each participant, and compliance with Good Clinical Practice and the Declaration of Helsinki is stated. All three applicable criteria are adequately addressed.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

Informed consent and regulatory compliance (GCP, Declaration of Helsinki) are stated, but the approving ethics bodies are not named and no approval numbers are given.

Evidence

paraphrase[Methods, Study oversight]

“The study protocol (available with the full text of this article at NEJM.org) was reviewed and approved by Independent Ethics Committees at each site and written informed consent was obtained from each participant.”

“The study is conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.”

MethodsFind in source

PASSReviewer 2· 90% conf

Ethics committee approval, written informed consent, and GCP/Declaration of Helsinki compliance are all stated.

Evidence

paraphrase[Methods, Study oversight]

“The study is conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.”

MethodsFind in source

PASSReviewer 3· 90% conf

Ethics approval by Independent Ethics Committees at each site, written informed consent, and compliance with GCP and the Declaration of Helsinki are all stated.

Evidence

paraphrase[Methods, Study oversight]

“The study is conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.”

MethodsFind in source

Mosnodenvir is identified as 10 mg, 50 mg, and 100 mg oral capsules with full loading/maintenance dose regimens, satisfying the investigational-product identification criterion. Statistical and PK software are identified with versions (SAS 9.04, R 4.2.0, Phoenix). The study does not use cell lines, antibodies, or laboratory animals, so those criteria are genuinely not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational product (mosnodenvir capsule strengths and dose regimens) and analysis software are identified; wet-lab reagents, cell lines, antibodies, and organisms are not applicable.

Evidence

“Mosnodenvir was supplied as 10 mg, 50 mg, and 100 mg oral capsules and administered under fasted conditions.”

MethodsFind in source

“Pharmacokinetic parameters, including maximum plasma concentration (C max ), time to C max (t max ), average concentration (C avg ), terminal elimination half-life (t ½ ) and area under the plasma concentration-time curve (AUC), were determined using the validated software Phoenix (Certara, Princeton, NJ, USA).”

MethodsFind in source

“Analyses were performed with SAS 9.04 (SAS Institute Inc., Cary, NC, USA). Graphs were created in R version 4.2.0”

Statistical analysisFind in source

PASSReviewer 2· 80% conf

The investigational product (mosnodenvir) is identified with formulation and dose/regimen, and analysis software is named with versions; bench-resource criteria are n/a.

Evidence

“Mosnodenvir was supplied as 10 mg, 50 mg, and 100 mg oral capsules and administered under fasted conditions.”

MethodsFind in source

“Analyses were performed with SAS 9.04 (SAS Institute Inc., Cary, NC, USA). Graphs were created in R version 4.2.0”

Statistical analysisFind in source

PASSReviewer 3· 80% conf

The investigational product (mosnodenvir) is identified with formulation and dose regimens, and analysis software is named with versions.

Evidence

“Mosnodenvir was supplied as 10 mg, 50 mg, and 100 mg oral capsules and administered under fasted conditions.”

MethodsFind in source

“Analyses were performed with SAS 9.04 (SAS Institute Inc., Cary, NC, USA). Graphs were created in R version 4.2.0”

Statistical analysisFind in source

Tobit ANOVA and exact Wilcoxon rank sum tests are named, with software identified and individual data points displayed. The reported p=0.001 for the Wilcoxon test is exact, but the primary Tobit result is only 'p<0.001,' which is imprecise. No point estimate or 95% CI for the high-dose versus placebo difference in log10 AUC is provided, leaving effect_sizes_ci not reported. The invalid table percentage '8.79.1' is a copyediting issue, not a statistical impossibility.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciNOT REPORTED

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Tests and software are named, individual data are shown, and no arithmetic impossibilities were found; however, the primary p-value is reported only as p<0.001 and no effect-size estimate with confidence interval is reported for the primary comparison.

Evidence

paraphrase[Results, Primary endpoint analysis]

“A Tobit analysis of variance showed a statistically significant reduction on the log 10 AUC D1-D29 VL in the high-dose mosnodenvir arm versus the placebo arm (2-sided p<0.001).”

“The statistically significant result was also seen by the exact Wilcoxon rank sum test (2-sided p=0.001).”

ResultsFind in source

“Solid black dots represent the individual log10 AUCD1-D29 (viral load) values.”

Figure 2Find in source

PASSReviewer 2· 75% conf

Tests are named, software identified, data shown with individual points and per-group n, and p-values are exact; the main gap is the absence of an effect estimate with confidence interval for the primary comparison.

Evidence

“A Tobit analysis of variance showed a statistically significant reduction on the log 10 AUC D1-D29 VL in the high-dose mosnodenvir arm versus the placebo arm (2-sided p<0.001)”

ResultsFind in source

“Solid black dots represent the individual log10 AUCD1-D29 (viral load) values.”

Figure 2Find in source

WARNReviewer 3· 75% conf

Tests are named, software identified, and data presented with individual points, but the primary p-value is printed only as a threshold and the primary effect size lacks a confidence interval.

Evidence

“A Tobit analysis of variance showed a statistically significant reduction on the log 10 AUC D1-D29 VL in the high-dose mosnodenvir arm versus the placebo arm (2-sided p<0.001)”

ResultsFind in source

“The statistically significant result was also seen by the exact Wilcoxon rank sum test (2-sided p=0.001).”

ResultsFind in source

“Solid black dots represent the individual log10 AUCD1-D29 (viral load) values.”

Figure 2Find in source

The paper mentions a protocol available at NEJM.org and ClinicalTrials.gov registration, but these are not data-availability mechanisms. There is no statement about access to individual participant data, no managed-access platform or data-access committee, and no deposit of viral sequencing data or analysis code. Because the trial generated human subject data and sequencing data, the data_availability_statement and related criteria are applicable and are not addressed.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

No data availability statement, repository deposit, accession numbers, or code-sharing mechanism is reported in the manuscript.

Evidence

paraphrase[Methods, Study oversight]

“The study protocol (available with the full text of this article at NEJM.org) was reviewed and approved by Independent Ethics Committees at each site”

absence[Entire manuscript]

No data-sharing statement is present.

FAILReviewer 2· 80% conf

No data availability statement is present; the paper only notes that the protocol is available at NEJM.org, which does not constitute a data-access route.

Evidence

paraphrase[Methods, Study oversight]

“The study protocol (available with the full text of this article at NEJM.org) was reviewed and approved by Independent Ethics Committees at each site”

absence[Full text (search for data availability)]

No statement of where or how study data can be accessed.

FAILReviewer 3· 85% conf

No data-availability statement is provided; the protocol is available at NEJM.org but no patient-level or study data access route is described.

Evidence

paraphrase[Methods, Study oversight]

“The study protocol (available with the full text of this article at NEJM.org)”

paraphrase[Methods, Study oversight]

“Data were gathered by the study site investigators and analyzed at Johnson & Johnson in collaboration with the NIH; no statement of data availability or access mechanism is provided.”

ClinicalTrials.gov registration (NCT05048875) is provided, methods are detailed with reference to a full protocol, and the Discussion explicitly notes CHIM limitations and the need for larger field studies. Funding and disclosure forms are stated. A CONSORT or other reporting guideline checklist is not mentioned, which is a minor transparency gap but does not undermine the manuscript's overall completeness.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Methods are sufficiently detailed, the trial is registered, outcomes appear consistently reported, limitations are discussed, conclusions are proportionate, and funding/COI are disclosed; no reporting checklist (e.g., CONSORT) is referenced.

Evidence

“ClinicalTrials.gov (https://ClinicalTrials.gov) number, NCT05048875 (https://clinicaltrials.gov/ct2/show/NCT05048875)”

MethodsFind in source

“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”

Discussion ¶5Find in source

“This study was funded in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) and Johnson & Johnson.”

FundingFind in source

PASSReviewer 2· 85% conf

Methods are detailed, the trial is registered (NCT05048875), outcomes are reported including negatives, limitations are discussed, conclusions are proportional, and funding/COI are disclosed; only a reporting-guideline (CONSORT) reference is missing.

Evidence

“ClinicalTrials.gov (https://ClinicalTrials.gov) number, NCT05048875 (https://clinicaltrials.gov/ct2/show/NCT05048875)”

MethodsFind in source

FundingFind in source

PASSReviewer 3· 85% conf

Trial registration, methods, funding/COI, limitations, and proportional conclusions are all reported; only a CONSORT-style reporting-guideline reference is missing.

Evidence

“ClinicalTrials.gov (https://ClinicalTrials.gov) number, NCT05048875”

MethodsFind in source

“Findings from those studies must be confirmed in larger safety and efficacy studies in the target population since CHIM studies do not reflect field conditions.”

DiscussionFind in source

FundingFind in source

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

NCT05048875

ClinicalTrials.gov

NCT05201794

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 38 references by DOI: 2 verified — 36 no DOI (shown, not verified).

NO DOI
Dengue
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The current and future global distribution and population at risk of dengue
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dengue emergency in the Americas: time for a new continental eradication plan
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Mosquito-borne diseases. An increasing risk in Europe
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Frequent outbreaks of dengue fever in South Asian countries-A correspondence analyzing causative factors and ways to avert
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dengue hemorrhagic fever - A systemic literature review of current perspectives on pathogenesis, prevention and control
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Clinical evaluation of dengue and identification of risk factors for severe disease: protocol for a multicentre study in 8 countries
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dengue guidelines for diagnosis, treatment, prevention and control: new edition
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Tracing down the Updates on Dengue Virus-Molecular Biology, Antivirals, and Vaccine Strategies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Development of TV003/TV005, a single dose, highly immunogenic live attenuated dengue vaccine; what makes this vaccine different from the Sanofi-Pasteur CYD vaccine?
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dengue Vaccines: An Update
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A guide to vaccinology: from basic principles to new developments
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Vaccines and antiviral drugs in pandemic preparedness
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Development of vaccines and antivirals for combating viral pandemics
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A pan-serotype antiviral to prevent and treat dengue: A journey from discovery to clinical development driven by public-private partnerships
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Blocking NS3-NS4B interaction inhibits dengue virus in non-human primates
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, Tolerability, and Pharmacokinetics of JNJ-1802, a Pan-serotype Dengue Direct Antiviral Small Molecule, in a Phase 1, Double-Blind, Randomized, Dose-Escalation Study in Healthy Volunteers
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genetically modified, live attenuated dengue virus type 3 vaccine candidates
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pharmacokinetics, safety, and tolerability of different maintenance dose regimens of mosnodenvir (JNJ-1802) in healthy adult participants
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Dengue human infection models to advance dengue vaccine development
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Evaluation of a new dengue 3 controlled human infection model for use in the evaluation of candidate dengue vaccines
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Viral kinetic modeling of mosnodenvir prophylaxis against DENV-3 in a controlled human infection model
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genomic surveillance reveals that the dengue 2 virus lineage responsible for the 2023-2024 epidemic in the French Caribbean Islands is resistant to Mosnodenvir
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Introducing the Bacterial and Viral Bioinformatics Resource Center (BV-BRC): a resource combining PATRIC, IRD and ViPR
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The Bacterial and Viral Bioinformatics Resource Center (BV-BRC)
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cocirculation of 4 Dengue Virus Serotypes, Putumayo Amazon Basin, 2023-2024
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Simultaneous Cocirculation of 2 Genotypes of Dengue Virus Serotype 3 Causing a Large Outbreak in Sri Lanka in 2023
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Detection of dengue virus serotype 4 in Panama after 23 years without circulation
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Assembling a comprehensive dataset to conduct an in-depth genomic investigation of the 2023-2024 dengue virus case surge in Valle del Cauca, Colombia
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Climate variation and serotype competition drive dengue outbreak dynamics in Singapore
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Seasonal variations in dengue virus transmission suitability in the Americas
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

4 data/code links checked; 3 live.

datahttps://clinicaltrials.gov/ct2/show/NCT05048875LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://clinicaltrials.gov/ct2/show/NCT05201794LIVEHTTP 200
Resolves, but the content could not be matched to the paper.
datahttps://NEJM.orgUNVERIFIEDHTTP 403
Liveness indeterminate — content not checked.
codehttp://cran.r-project.org/LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

Copyediting

1 finding · worst low

Wording, consistency and formatting errors that need correcting before submission.

Wording or formatting errors that need correctingAssessed

9 copyedit issues flagged (1 major): mostly consistency, other, typo.

MAJORconsistencyTable 1, Race row 'Multiple', Combined mosnodenvir column
“2 (8.79.1)”
→ 2 (9.1)
2 out of 22 participants is 9.1%, not 8.79.1%; the string '8.79.1' is invalid.
MINORclarityMethods, Statistical analysis, paragraph 1
“The primary efficacy analysis included all participants from Cohort 1 Group 1 who were inoculated with rDEN3Δ30.”
→ Clarify whether the primary efficacy set is Group 1 only or all Cohort 1 arms; Table 1 reports an efficacy analysis set of 29 across all arms.
Potential mismatch between the stated primary analysis set and the efficacy analysis set in Table 1.
MINORgrammarTable 2, footnote §
“Solicited systemic AEs events reported from challenge up to and including the D43 visit”
→ Solicited systemic AE events reported from challenge up to and including the D43 visit
Redundant 'AEs events' construction.
MINORotherEnd of manuscript, footer area
“as. 2022;17(6) Associated Data Supplementary Materials Supplement”
→ Remove stray citation/header text or format as a proper reference.
Appears to be a leftover citation fragment.
MINORtypoTable 1, Race row 'Multiple'
“2 (8.79.1)”
→ 2 (9.1)
Malformed percentage; 2/22 = 9.1%.
MINORtypoAuthor affiliation 1
“1 John Hopkins Bloomberg School of Public Health”
→ Johns Hopkins Bloomberg School of Public Health
Institution name misspelled.
MINORconsistencyEnd of manuscript body
“as. 2022;17(6) Associated Data Supplementary Materials Supplement”
→ Remove stray citation/formatting fragment
Leftover text fragment appears after the footnotes.
MINORotherTable 2 footnotes
“Solicited systemic AEs events reported from challenge up to and including the D43 visit are excluded from as they are considered...”
→ Clean up the sentence fragment ('excluded from [Table] as they are considered...')
Awkward/fragmentary phrasing in the footnote.
MINORconsistencyTable 2A
“2 (33.3%)”
→ 2 (33.3)
Inconsistent use of '%' in some cells of the same column (minor formatting inconsistency).

Full text (33,563 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorReviewer 3

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

Daily Mosnodenvir as Dengue Prophylaxis in a Controlled Human Infection Model.

DOI

10.1056/NEJMoa2500179

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-22