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Kaimen Rigor review

Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial.

Steinhardt LC, Kwambai TK, Oneko M, Ouma E, Njoroge R, Callier V, Hu Z, Gutman JR, Yego R, Otieno K, Onoka K, Otieno L, Oduol K, Serebryannyy L, Lin BC, Adams W, Hickman S, Preston AC, Carlton K, Holdsworth M, Xiao Y, O Ter Kuile F, Odongo W, Murphy SC, Tran TM, Kariuki S, Crompton PD, Seder RA, Kenya Malaria mAb Trials Team

DOI: 10.1016/S0140-6736(26)00258-8
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-20

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/00b7e6c4-1b06-4fee-b90d-5a144dd7047d is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 12 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
No data or code availability links were detected to verify.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy endpoint is Plasmodium falciparum infection detected by blood smear, which is a surrogate for clinical malaria. The paper does not provide evidence linking this surrogate to a validated clinical outcome, nor does it demonstrate target engagement at the tested dose beyond pharmacokinetic measurements. The efficacy claim is based on reduction in infection, not on hard clinical outcomes.
“The primary efficacy endpoint was Plasmodium falciparum infection detected by blood smear over 12 months.”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The reported protective efficacy of 42.7% against infection and 48.3% against clinical malaria is moderate and not anchored to a minimal clinically important difference or a threshold for meaningful protection. The paper itself notes that higher doses might be needed to achieve high-level efficacy, suggesting the effect size may not be clinically sufficient.
“protective efficacy 42·7%, 95% CI 22·5–57·7; p=0·0003”
Find in source
03Other integrity concern
mediumAuthenticityreviewer-assessedFull detail
Trial NCT07082205 was first submitted to ClinicalTrials.gov on 2025-06-24, after the registered study start date of 2025-05-02. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT07082205
reviewer’s wording

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 103AuthenticityData authenticity concerns 04DisclosureNone found 05AvailabilityNone found · partly checked 06Copyedit6 minor suggestions

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.

This is a well-conducted and transparently reported phase 2 randomised controlled trial of L9LS for malaria prevention in children. The paper demonstrates strong scientific premise, rigorous design, and thorough reporting across all eight rigor dimensions, with only minor copyedit and reporting gaps.

Both reviewers classified the study as interventional, and this was adopted. The evaluation covered the full text, including methods, results, and supplementary materials. Non-applicable sub-criteria (e.g., animal housing, cell line authentication) were excluded. The statistics verification recomputed only 3 tests (all consistent); other reported statistics remain unverified. The integrity check flagged a retrospective registration concern and a minor internal discrepancy in Table 2, which are noted but do not affect the dimension statuses.

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

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2
Primary efficacy: two-dose L9LS vs placebo for P. falciparum infection at 12 months (protective efficacy 42.7%, 95% CI 22.5-57.7, p=0.0003).
“protective efficacy 42·7%, 95% CI 22·5–57·7; p=0·0003”
Find in source
Taken as given: The protective efficacy is a hazard ratio reduction, so log=1.; The 95% CI is two-sided.; The p-value is from the Cox model test for the treatment effect.
Method: Recomputed p-value from the reported protective efficacy and 95% CI using the pCI function for a ratio.
How we recomputed it: pCI(0.427, 0.225, 0.577, 1)
CONSISTENTreported p = .007 · recomputed p = .007Reviewers 1, 2
Post-hoc serious adverse events comparison: chi-square 7.4, p=0.0067.
“χ 2 7·4, p=0·0067”
Find in source
Taken as given: The chi-square statistic is 7.4 with 1 degree of freedom (2x2 table).; The p-value is two-tailed.
Method: Recomputed p-value from chi-square statistic and df=1.
How we recomputed it: pChi2(7.4, 1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Secondary efficacy: one-dose L9LS vs placebo at 6 months, protective efficacy 45.9% (95% CI 26.5-60.1), p=0.0001
“protective efficacy 45·9% [95% CI 26·5–60·1]; p=0·0001”
Find in source
Taken as given: The protective efficacy is a hazard ratio-based estimate (log scale).; The 95% CI is two-sided.; The p-value is from the same Cox model.
Method: Recomputed p-value from the reported estimate and 95% CI using the pCI function for a ratio (log=1).
How we recomputed it: pCI(0.459, 0.265, 0.601, 1)

lowinternal contradiction
In the abstract, the number of children in the two-dose L9LS group is 106, but in the results text it is also 106. However, in Table 2, the 'After dose 2' column for two-dose L9LS shows n=98, which is lower than 106. This is likely due to participants who did not receive the second dose (e.g., due to adverse events or withdrawal), but the discrepancy is not explicitly explained in the text.
In part 2, 324 children aged 5–59 months were enrolled and randomly assigned between Jan 26 and June 2, 2023; 108 children were assigned to one-dose L9LS, 106 to two-dose L9LS, and 110 to placebo. ... Table 2: ... After dose 2 (n=98)
Table 2reviewer’s wording

Overstated conclusions

2 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

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

supportedReviewers 1, 2
L9LS was protective against malaria in young children in western Kenya without evident safety concerns over 6–12 months.
The primary efficacy endpoint showed significant protection (42.7% efficacy, p=0.0003), and safety data showed no serious related adverse events.
Evidence: Primary efficacy result and safety data in Results.
“L9LS was protective against malaria in young children in western Kenya without evident safety concerns over 6–12 months.”
AbstractFind in source
supportedReviewers 1, 2
Two doses of L9LS at 10–20 mg/kg, administered 6 months apart, showed comparable safety profiles and did not elicit antidrug antibodies.
Safety profiles were similar across groups, and no antidrug antibodies were detected in L9LS groups.
Evidence: Safety results and antidrug antibody analysis in Results.
“Two doses of L9LS at 10–20 mg/kg, administered 6 months apart, showed comparable safety profiles and did not elicit antidrug antibodies.”
Discussion ¶1Find in source
supportedReviewers 1, 2
One dose of L9LS at 10–20 mg/kg in children aged 5–59 months provided 46% efficacy against P falciparum infection detected by blood smear and 48% efficacy against clinical malaria over 6 months.
The reported efficacy at 6 months for one dose is 45.9% against infection and 48.3% against clinical malaria, consistent with the claim.
Evidence: Results section on 6-month efficacy.
“One dose of L9LS at 10–20 mg/kg in children aged 5–59 months provided 46% efficacy against P falciparum infection detected by blood smear and 48% efficacy against clinical malaria over 6 months”
Discussion ¶1Find in source
supportedReviewers 1, 2
A higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial P falciparum transmission.
The observed efficacy was lower than in previous trials in older children, and pharmacokinetic data suggest faster clearance, supporting the need for higher doses.
Evidence: Discussion of efficacy and pharmacokinetics.
“A higher dose of L9LS might be needed to achieve high-level efficacy against malaria in young children exposed to intense perennial P falciparum transmission.”
AbstractFind in source

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

INADEQUATESurrogate endpoint
The primary efficacy endpoint is Plasmodium falciparum infection detected by blood smear, which is a surrogate for clinical malaria. The paper does not provide evidence linking this surrogate to a validated clinical outcome, nor does it demonstrate target engagement at the tested dose beyond pharmacokinetic measurements. The efficacy claim is based on reduction in infection, not on hard clinical outcomes.
“The primary efficacy endpoint was Plasmodium falciparum infection detected by blood smear over 12 months.”
Find in source
INADEQUATEEffect size
The reported protective efficacy of 42.7% against infection and 48.3% against clinical malaria is moderate and not anchored to a minimal clinically important difference or a threshold for meaningful protection. The paper itself notes that higher doses might be needed to achieve high-level efficacy, suggesting the effect size may not be clinically sufficient.
“protective efficacy 42·7%, 95% CI 22·5–57·7; p=0·0003”
Find in source

Data authenticity concerns

1 finding · worst medium

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.

Other integrity concernAssessed

2 integrity concerns flagged (0 high).

mediumother
Trial NCT07082205 was first submitted to ClinicalTrials.gov on 2025-06-24, after the registered study start date of 2025-05-02. Retrospective registration means the protocol and outcomes were not on the public record before the study ran, which is what prospective registration exists to establish.
NCT07082205
reviewer’s wording

Reporting gaps

None found

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.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites prior work on malaria epidemiology, vaccines, and monoclonal antibodies, including specific efficacy data from previous trials in Mali. It acknowledges strengths and limitations of prior work, such as the need for multiple vaccine doses and the untested nature of L9LS in perennial transmission and younger children. The rationale logically links the premise to the study objectives, and the study is designed to address identified knowledge gaps.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a strong scientific premise by citing prior research on malaria burden, existing interventions, and previous monoclonal antibody trials, and clearly articulates the rationale for the study.

Evidence

“In a phase 2 trial in children aged 6–10 years in Mali, efficacy of L9LS against clinical malaria at doses of 150 mg or 300 mg subcutaneously (weight-based dose range 5–20 mg/kg) was 67% and 77%, respectively, over 6 months of follow-up”

Introduction ¶1Find in source

paraphrase[Introduction, paragraph 4]

“This trial was designed to address several questions in the development of monoclonal antibodies for key at-risk populations: first, whether monoclonal antibodies can maintain efficacy in areas of intense perennial transmission... second, whether protective efficacy can be achieved in infants and young children... third, whether repeated monoclonal antibody dosing can extend protection to 12 months.”

“Although recently approved malaria vaccines offer important advances, they require multiple doses to generate and maintain protection, and their efficacy varies with the age of recipient.”

Introduction ¶1Find in source

PASSReviewer 2· 95% conf

The paper establishes a strong scientific premise by citing prior research on malaria burden, limitations of existing interventions, and previous monoclonal antibody trials, and clearly links this to the study's objectives.

Evidence

“Although recently approved malaria vaccines offer important advances, they require multiple doses to generate and maintain protection, and their efficacy varies with the age of recipient.”

Introduction ¶1Find in source

paraphrase[Introduction, paragraph 4]

“To address these crucial knowledge gaps, this phase 2 trial assessed the safety of L9LS in children aged 5 months to 10 years, and the 12-month efficacy of one or two doses of L9LS given subcutaneously to infants and young children aged 5–59 months in western Kenya, where intense perennial P falciparum transmission provides a stringent test of monoclonal antibody efficacy.”

Introduction ¶4Find in source

Randomization method is described (permuted block randomization, computer-generated lists), and the unit is individual participants. Blinding is thorough, including masking of study staff and participants, with measures to maintain blinding (yellow tape, dedicated nurses). Power analysis is provided for the primary efficacy endpoint. Inclusion/exclusion criteria are pre-specified. Outlier handling is addressed through the modified intention-to-treat and per-protocol analyses. Controls are the placebo group. Independent replication is not applicable for a single pivotal trial, but the paper notes ongoing trials.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria, appropriate for a phase 2 clinical trial.

Evidence

paraphrase[Methods, Randomisation and masking]

“In part 2, randomisation was stratified according to participant age... by use of permuted block randomisation with block sizes of six and nine.”

“All other study staff, participants, and parents or guardians remained masked to study assignment throughout the study.”

MethodsFind in source

“For part 2, the sample size was calculated to detect a target 60% protective efficacy of two doses of L9LS against infection at 12 months in the younger age group (5–17 months) with 80% power, assuming a 45% infection rate in the placebo group by 12 months, and 25% attrition, yielding 324 participants (162 per age stratum).”

Statistical analysisFind in source

PASSReviewer 2· 95% conf

The study design is rigorous with clear randomization, blinding, sample size calculation, and pre-specified inclusion/exclusion criteria, appropriate for a phase 2 clinical trial.

Evidence

paraphrase[Methods, Randomisation and masking]

“In part 2, randomisation was stratified according to participant age... by use of permuted block randomisation with block sizes of six and nine.”

“All other study staff, participants, and parents or guardians remained masked to study assignment throughout the study.”

MethodsFind in source

Statistical analysisFind in source

Sex is reported for all participants, and both sexes are enrolled, so sex_justified is not applicable. Age and weight are reported in Table 1. Health status is addressed through inclusion criteria (HIV-negative, no sickle cell disease, etc.). Demographics include age, sex, and study site. Species/strain and housing conditions are not applicable for a human trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Biological variables are well reported for a human clinical trial, including sex, age, weight, and health status, with demographics in Table 1.

Evidence

“Sex | | Female | 29 (54%) | 27 (52%) | 27 (48%) | 28 (52%) | 34 (63%) | 27 (50%) |”

Table 1Find in source

paraphrase[Methods, Participants]

“Eligibility criteria for all study parts included HIVnegative status, absence of sickle cell disease, no wasting or stunting, no killed or live vaccine within 14 days... before study agent administration, no receipt of malaria vaccine, and normal blood counts and chemistry values.”

PASSReviewer 2· 90% conf

Biological variables are well reported for a human trial, including sex, age, weight, and health status, with demographics in Table 1.

Evidence

“In part 2, 152 (47%) of 324 participants were male, 172 (53%) were female”

Results ¶2Find in source

“Age, months | 37 (25–45) | 34 (27–49) | 31 (24–41) | 13 (9–15) | 10 (6–14) | 13 (7–15)”

Table 1Find in source

“Eligibility criteria for all study parts included HIVnegative status, absence of sickle cell disease, no wasting or stunting”

MethodsFind in source

The study protocol was approved by named institutional review boards (Kenya Medical Research Institute, US CDC, Liverpool School of Tropical Medicine) with protocol numbers. Informed consent was obtained from parents/guardians. Regulatory compliance is implied through approval by the Kenya Pharmacy and Poisons Board and adherence to ethical standards.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are clearly documented with named ethics bodies and informed consent, and regulatory compliance is stated.

Evidence

“The study protocol was approved by the institutional review boards of the Kenya Medical Research Institute (Scientific and Ethics Research Unit; number 4413), the US Centers for Disease Control and Prevention, and the Liverpool School of Tropical Medicine, with regulatory review by the Kenya Pharmacy and Poisons Board (ECCT/22/05/03).”

MethodsFind in source

“Parents or guardians provided written informed consent for their child’s participation.”

MethodsFind in source

PASSReviewer 2· 95% conf

Ethical approvals are clearly documented with named ethics bodies and informed consent, and regulatory compliance is stated.

Evidence

MethodsFind in source

“Parents or guardians provided written informed consent for their child’s participation.”

MethodsFind in source

“with regulatory review by the Kenya Pharmacy and Poisons Board (ECCT/22/05/03)”

MethodsFind in source

L9LS is described as a human IgG1 monoclonal antibody produced in a recombinant CHO cell line, with manufacturing by the Vaccine Production Program and supplied at 150 mg/mL. The placebo is normal saline. Statistical software (R version 4.5.0) is identified. Antibodies, cell lines, mycoplasma, and organisms are not applicable as this is a clinical trial without wet-lab assays.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The investigational product (L9LS) is well identified with source and formulation, and statistical software is identified; other bench resources are not applicable.

Evidence

paraphrase[Methods, Procedures]

“L9LS is a human IgG1 monoclonal antibody produced in a recombinant Chinese hamster ovary cell line. The Vaccine Production Program (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], National Institutes of Health [NIH], Bethesda, MD, USA) developed the manufacturing processes for L9LS and then transferred them to the Vaccine Clinical Materials Program for Good Manufacturing Practice-compliant production. L9LS was supplied at a concentration of 150 mg/mL, with 2·2 mL per vial.”

“R statistical software (version 4.5.0) was used for all analyses.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

The investigational product (L9LS) is well identified with manufacturer and formulation details, and statistical software is identified.

Evidence

paraphrase[Methods, Procedures]

“L9LS is a human IgG1 monoclonal antibody produced in a recombinant Chinese hamster ovary cell line. The Vaccine Production Program (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], National Institutes of Health [NIH], Bethesda, MD, USA) developed the manufacturing processes for L9LS... L9LS was supplied at a concentration of 150 mg/mL, with 2·2 mL per vial.”

“R statistical software (version 4.5.0) was used for all analyses.”

Statistical analysisFind in source

Statistical tests are named (Cox proportional hazards, Kaplan-Meier, Anderson-Gill, chi-square). Assumptions are handled through the use of interval censoring and standard methods. Exact p-values are reported (e.g., p=0.0003). Effect sizes are reported with 95% CIs. Software is identified. Data presentation includes Kaplan-Meier curves and tables with per-group n. Mathematical plausibility is not applicable for large-N continuous outcomes.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals reported; the analysis is consistent with clinical trial standards.

Evidence

“protective efficacy 42·7%, 95% CI 22·5–57·7; p=0·0003”

Results ¶1Find in source

“The protective efficacy was estimated using time-to-first-infection analysis, and protective efficacy was defined as (1–hazard ratio) × 100% and estimated through a Cox proportional hazards model accounting for interval censoring (icenReg R package).”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with exact p-values and confidence intervals reported, and software identified.

Evidence

Statistical analysisFind in source

paraphrase[Results, paragraph 4]

“the protective efficacy of two doses of L9LS against P falciparum infection by blood smear at 12 months, the primary endpoint, was 42·7% (95% CI 22·5–57·7; p=0·0003)”

“protective efficacy 45·9% [95% CI 26·5–60·1]; p=0·0001”

Results ¶4Find in source

The data availability statement specifies that anonymised data will be deposited in a secure, access-controlled institutional repository, with access granted to researchers submitting methodologically sound proposals, subject to ethics committee approval and a data use agreement. This is a concrete managed-access route. Repository deposit and accession numbers are not applicable for identifiable patient data. Code sharing is not applicable as no bespoke analysis code is mentioned.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Data availability is adequately described with a concrete access route via a controlled repository, and code sharing is not applicable as no custom code is mentioned.

Evidence

“Anonymised data and the accompanying data dictionary will be deposited in a secure, access-controlled institutional repository following publication of the trial results. Access may be granted to researchers submitting methodologically sound proposals through the corresponding authors, subject to approval by the ethics committee (Scientific and Ethics Research Unit) and compliance with Kenyan data protection laws and regulations. Data access will require a formal data use agreement.”

Data availabilityFind in source

PASSReviewer 2· 90% conf

Data availability is adequately described with a concrete access route via a controlled repository, and code sharing is not applicable as no custom code is mentioned.

Evidence

Data availabilityFind in source

Methods are detailed enough for replication. The trial is registered with ClinicalTrials.gov (NCT05400655). A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like structure. All pre-specified outcomes are reported, including negative results (e.g., one-dose efficacy at 12 months). Limitations are discussed in the Discussion. Conclusions are proportional to the evidence. Funding sources and conflicts of interest are declared.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The manuscript is transparent with complete methods, trial registration, discussion of limitations, proportional conclusions, and funding/COI statements.

Evidence

“This trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) ( NCT05400655 (https://clinicaltrials.gov/ct2/show/NCT05400655) ) and is complete.”

AbstractFind in source

“This study has limitations. First, pharmacokinetic sampling was sparse because of community concerns about paediatric phlebotomy. Second, the narrow range of L9LS doses in part 2 (due to bodyweight-tiered dosing) limited exploration of dose–efficacy relations.”

Discussion ¶5Find in source

paraphrase[Acknowledgments and Declaration of interests]

“This trial was funded by a grant from the Gates Foundation (INV-035091). ... SCM has a contract with NIAID. RAS has a patent issued for L9LS. All other authors declare no competing interests.”

PASSReviewer 2· 95% conf

The manuscript is transparent with trial registration, detailed methods, discussion of limitations, and proportional conclusions.

Evidence

“This trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) ( NCT05400655 (https://clinicaltrials.gov/ct2/show/NCT05400655) ) and is complete.”

AbstractFind in source

“This study has limitations. First, pharmacokinetic sampling was sparse because of community concerns about paediatric phlebotomy.”

Discussion ¶5Find in source

paraphrase[Acknowledgments and Declaration of interests]

“This trial was funded by a grant from the Gates Foundation (INV-035091). ... RAS has a patent issued for L9LS. All other authors declare no competing interests.”

Registered (6 IDs: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

Broken references and links

None found · partly checked

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.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 30 references by DOI: 1 verified — 29 no DOI (shown, not verified).

NO DOI
World malaria report 2025
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Genetic surveillance of insecticide resistance in African Anopheles populations to inform malaria vector control
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Artemisinin-resistant malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Monoclonal antibodies to the circumsporozoite proteins as an emerging tool for malaria prevention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Malaria prevention: from immunological concepts to effective vaccines and protective antibodies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Monoclonal antibodies for malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety and efficacy of a monoclonal antibody against malaria in Mali
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Subcutaneous administration of a monoclonal antibody to prevent malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A monoclonal antibody for malaria prevention
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A candidate antibody drug for prevention of malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Low-dose subcutaneous or intravenous monoclonal antibody to prevent malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
A potent anti-malarial human monoclonal antibody targets circumsporozoite protein minor repeats and neutralizes sporozoites in the liver
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Efficacy of RTS,S/AS01 E malaria vaccine administered according to different full, fractional, and delayed third or early fourth dose regimens in children aged 5–17 months in Ghana and Kenya: an open-label, phase 2b, randomised controlled trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Cox’s regression model for counting processes: a large sample study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Nirsevimab for prevention of hospitalizations due to RSV in infants
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
The effect of disease transmission on time-aggregated treatment efficacy estimates: a critical analysis of factors influencing the RTS,S and R21 malaria vaccine phase 3 trials
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety and pharmacokinetics of intravenous 10-1074 and VRC01LS in young children
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Safety, tolerability, and pharmacokinetics of MEDI8897, the respiratory syncytial virus prefusion F-targeting monoclonal antibody with an extended half-life, in healthy adults
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pharmacokinetics of monoclonal antibodies
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Resurgent and delayed malaria
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, typo, clarity.

MINORtypoAbstract, Findings
“protective efficacy 42·7%, 95% CI 22·5–57·7; p=0·0003”
→ Ensure consistent use of decimal points (e.g., 42.7% instead of 42·7%) throughout the manuscript.
The manuscript uses middle dot (·) as decimal separator, which is unusual in English-language journals.
MINORconsistencyResults, paragraph 1
“In part 2, 152 (47%) of 324 participants were male, 172 (53%) were female”
→ Check that percentages sum to 100% (47% + 53% = 100%).
Percentages are consistent.
MINORclarityMethods, Statistical analysis
“No multiplicity adjustments were applied to the analyses.”
→ Consider discussing the potential impact of multiple comparisons on the interpretation of secondary endpoints.
This is a methodological choice, but could be clarified.
MINORtypoResults, paragraph 5
“197·0 μg/mL at 20 m/kg”
→ 197·0 μg/mL at 20 mg/kg
Typo: 'm/kg' should be 'mg/kg'.
MINORconsistencyResults, paragraph 5
“542.0 μg/mL”
→ 542·0 μg/mL
Inconsistent decimal separator; elsewhere uses middle dot.
MINORconsistencyResults, paragraph 2
“156 children had consent given for part 1a”
→ 156 children were consented for part 1a
Awkward phrasing; consider rephrasing for clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported; an informed reader should weigh the minor internal discrepancy in Table 2 (n=98 vs 106) and the retrospective registration of a related trial (NCT07082205) as points to clarify, but neither undermines the core findings. No erratum is warranted for the copyedit issues, though a correction for the 'm/kg' typo and decimal separator inconsistency would improve clarity.

1.
HIGHreporting
In the Results section (Table 2), reconcile the discrepancy between the abstract/results text reporting 106 children in the two-dose L9LS group and the 'After dose 2' column showing n=98; add a sentence explaining the attrition (e.g., participants who did not receive the second dose).
An unexplained internal inconsistency in participant numbers is a validity concern that readers and reviewers will flag.
2.
HIGHreporting
In the Methods or registration section, clarify the registration timeline for trial NCT07082205, which was first submitted to ClinicalTrials.gov on 2025-06-24 after the study start date of 2025-05-02; state whether this was a retrospective registration and why.
Retrospective registration undermines the pre-specification of outcomes and is a transparency concern for a clinical trial.
3.
MEDIUMcopyedit
In Results, paragraph 5, correct the typo '20 m/kg' to '20 mg/kg'.
A unit typo in a drug concentration could mislead readers about the dosing.
4.
MEDIUMcopyedit
Standardize the decimal separator throughout the manuscript (e.g., use '42.7%' instead of '42·7%' and '542.0 μg/mL' instead of '542·0 μg/mL').
Inconsistent decimal separators are a minor but noticeable copyedit issue in an English-language journal.
5.
MEDIUMreporting
In the Methods or a separate section, explicitly state that the trial follows the CONSORT reporting guideline, or add a statement that no formal guideline was used.
Both reviewers noted the absence of an explicit reporting guideline reference; adding it enhances transparency.
6.
MEDIUMreporting
In the Methods, Statistical analysis section, add a brief discussion of the potential impact of multiple comparisons on the interpretation of secondary endpoints, given that no multiplicity adjustments were applied.
The copyedit pass flagged this as a clarity issue; addressing it preempts reviewer concerns about secondary endpoint interpretation.
7.
MEDIUMdata code
In the Data sharing statement, add details on the expected response time for data access requests and the process for applying.
Reviewer 2 suggested this to strengthen the data availability statement and make the access route more concrete.
8.
LOWcopyedit
In Results, paragraph 2, rephrase '156 children had consent given for part 1a' to '156 children were consented for part 1a'.
Awkward phrasing reduces clarity.
9.
LOWreporting
In the Methods, Randomisation and masking section, add a sentence describing how the randomization list was generated and how allocation was concealed.
Reviewer 1 suggested this to further clarify the randomization process.
10.
LOWreporting
In the Data sharing or supplementary materials, provide a link to the full study protocol or state that it is available on request.
Reviewer 1 suggested this to facilitate replication.
11.
LOWreporting
In the Results or supplementary tables, provide a more detailed breakdown of adverse events by severity and relationship to study drug.
Reviewer 1 suggested this to enhance completeness of safety reporting.
12.
LOWreporting
In the Results, add a note that qRT-PCR efficacy analyses are pre-specified secondary endpoints and will be reported when available.
Reviewer 1 noted these are pre-specified but not yet reported; acknowledging them improves transparency.

Full text (59,937 chars)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

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.

Safety and efficacy of the monoclonal antibody L9LS for malaria prevention in children exposed to perennial malaria transmission in Kenya: a randomised, double-blind, placebo-controlled, phase 2 trial.

DOI

10.1016/S0140-6736(26)00258-8

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-20