Verified Rigor RecordRigor Reviewed

Rigor-Reviewed Manuscript

Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial.

Name: Verified Rigor Record — Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial.
Item: Anti-CD38 monoclonal antibody CM313 for primary immune thrombocytopenia: multicentre, randomised, placebo controlled, phase 2 trial.
Rating: 100
Author: Αlpha¹

Chen Y, Xu Y, Dai J, Sun T, Li H, Hua Z, Zhou Z, Zhou H, Yan Z, Zhao X, Xue F, Liu W, Liu X, Fu R, Wang W, Chi Y, Dong H, Ju M, Dai X, Gu W, Pei X, Yang R, Zhang L

Paper source

Open DOI

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 7, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

PASS

Passes rigor review · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: highEngine: 7.6.0Source: full text

This Αlpha¹ Rigor Review uses AI 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-designed and clearly reported phase 2 trial. The main methodological strength is the rigorous study design (randomised, blinded, with a pre-specified power analysis). The primary weakness is the code sharing being limited to supplemental files without a public repository, which the authors should fix before submission for full reproducibility. A few minor reporting gaps (missing CONSORT statement reference, p-value reported as threshold) are worth addressing but are not likely to cause rejection.

All three independent reviewers (AI models) scored the full-text manuscript. The study is a human clinical trial, so several sub-criteria (replicate distinction, controls, independent replication, species/strain, housing, IACUC) are correctly marked not applicable. The statistics verification component checked 8 reported values (all consistent); coverage is partial, and no arithmetic errors were found. The copyedit pass flagged 6 minor issues (grammar, clarity, formatting). The citation check found no retracted or unfindable references. One reproducibility link was dead (code repository link?), but this is a low-severity issue since code is in supplemental files.

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

Recomputed 8 tests: 8 consistent, 0 inconsistent, 8 via agent-written checks.

Rigor

Eight Dimensions8 pass

11 major claims3 partial8 supported

The introduction cites prior research on immune thrombocytopenia and CD38-targeted therapies, including phase 1/2 trial results for CM313. A logical rationale links CD38 expression on plasma cells to the study objectives. Limitations of prior research (e.g., need for innovative treatments due to heterogeneity and refractoriness) are addressed, and the study builds directly on previous single-arm trial findings.

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 by citing prior work on immune thrombocytopenia pathophysiology, the role of CD38, and previous studies of anti-CD38 antibodies including a phase 1/2 trial of CM313.

Evidence

direct quote[Introduction, paragraph 3]

“Preliminary results from our previous single arm phase 1/2 trial highlighted the promising efficacy and tolerable safety profile of CM313 in patients with previously treated immune thrombocytopenia.”

direct quote[Introduction, paragraph 3]

“CD38, a type II glycoprotein abundantly expressed on antibody-producing plasmablasts and plasma cells, represents a promising therapeutic target in autoimmune diseases.”

direct quote[Introduction, paragraph 3]

“Building on these findings, this study presents data from a randomised, placebo controlled, phase 2 trial evaluating the safety and efficacy of CM313 in patients with immune thrombocytopenia who had received multiple previous treatments.”

PASSReviewer 2· 85% conf

The scientific premise is well-established with prior work cited and a logical rationale, though limitations of prior research are not explicitly addressed.

Evidence

direct quote[Introduction, paragraph 4]

direct quote[Introduction, paragraph 3]

“CD38, a type II glycoprotein abundantly expressed on antibody-producing plasmablasts and plasma cells, represents a promising therapeutic target in autoimmune diseases.”

PASSReviewer 3· 100% conf

The paper clearly establishes its scientific foundation by citing prior research, explaining the rationale, and addressing limitations of prior work.

Evidence

direct quote[Introduction, paragraphs 3-4]

“Anti-CD38 monoclonal antibodies, such as mezagitamab and daratumumab, have shown efficacy not only in immune thrombocytopenia but also in other autoantibody mediated diseases...”

direct quote[Introduction, paragraph 3]

“CD38, a type II glycoprotein abundantly expressed on antibody-producing plasmablasts and plasma cells, represents a promising therapeutic target in autoimmune diseases.”

direct quote[Introduction, paragraph 2]

“...the heterogeneity of immune thrombocytopenia and the persistence of therapeutic refractoriness in certain patients underscore the urgent need for innovative and effective treatment strategies.”

Randomization used SAS-generated block randomization. Blinding was maintained with indistinguishable formulations and an independent data collection team. A priori power analysis with assumptions was reported. Inclusion/exclusion criteria were specified. Outlier handling was addressed through ITT analysis and rescue treatment rules.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study design is well-described for a phase 2 clinical trial, with adequate reporting of randomisation, blinding, sample size calculation, inclusion/exclusion criteria, and statistical analysis plan.

Evidence

direct quote[Methods, Randomisation and masking]

“Using SAS software, a statistician applied a block size of three to generate the randomisation list for patients.”

direct quote[Methods, Randomisation and masking]

“To maintain blinding, both CM313 and placebo were visually indistinguishable. A dedicated team responsible for ensuring blinding integrity throughout the trial managed allocation concealment... An independent team, separate from the investigators, collected all the data...”

direct quote[Methods, Statistical analysis]

“Based on a previous study, assuming a response rate of 70% for CM313 at week 8 and a spontaneous remission rate of 18% for placebo, we required a sample size of 39 participants (allocated 2:1) to provide a power of 80% to detect a difference between groups at a two sided α level of 0.05.”

PASSReviewer 2· 95% conf

Study design is rigorous, with adequate randomization, blinding, power analysis, inclusion/exclusion criteria, and handling of missing data.

Evidence

direct quote[Methods, Randomisation and masking]

“Using SAS software, a statistician applied a block size of three to generate the randomisation list for patients.”

direct quote[Methods, Randomisation and masking]

“Both CM313 and placebo were visually indistinguishable.”

direct quote[Methods, Statistical analysis]

PASSReviewer 3· 95% conf

The trial design is rigorous with adequate randomization, blinding, power analysis, and pre-specified criteria, scoring ≥60% of applicable sub-criteria as adequate.

Evidence

direct quote[Methods, Randomisation and masking]

“Using SAS software, a statistician applied a block size of three to generate the randomisation list for patients.”

direct quote[Methods, Randomisation and masking]

“To maintain blinding, both CM313 and placebo were visually indistinguishable. ... An independent team, separate from the investigators, collected all the data...”

direct quote[Methods, Statistical analysis]

“Based on a previous study, assuming a response rate of 70% for CM313 at week 8 and a spontaneous remission rate of 18% for placebo, we required a sample size of 39 participants... to account for an anticipated drop-out rate of 15%, we planned to enrol a total of 45 patients.”

Sex is reported (60% female CM313, 73% placebo). Age is reported as median (IQR). Demographics include age, sex, BMI, and baseline clinical characteristics. Since both sexes are included, a sex justification is not required and is marked not_applicable. Species/strain and housing are not applicable to a human trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key biological variables for a human clinical trial are adequately reported, including age, sex, and baseline disease characteristics.

Evidence

direct quote[Table 1]

“Median (IQR) age (years) | 38.5 (29.0-52.0) | 45.0 (25.0-52.0) | 41.0 (29.0-52.0)”

direct quote[Table 1]

“Female | 18 (60) | 11 (73) | 29 (64)”

direct quote[Table 1]

“Median (IQR) duration of ITP (years) | 3.7 (0.8-6.1) | 7.0 (4.0-10.3) | 4.5 (0.8-8.0)”

PASSReviewer 2· 85% conf

Biological variables are adequately reported, including sex, age, and health status; however, race/ethnicity is not tabulated per participant.

Evidence

direct quote[Table 1]

“Sex*: Male 12 (40), Female 18 (60)”

direct quote[Table 1 and Results]

“Median age was 38.5 years (interquartile range (IQR) 29.0-52.0) in the CM313 group”

absence[Table 1]

Race/ethnicity not individually tabulated.

PASSReviewer 3· 100% conf

All applicable biological variables for a human interventional trial are reported and adequate.

Evidence

direct quote[Results, Table 1]

“Female: CM313 group 18 (60%), Placebo group 11 (73%)”

direct quote[Results, paragraph 2 and Table 1]

“Median age was 38.5 years (interquartile range (IQR) 29.0-52.0) in the CM313 group and 45.0 (25.0-52.0) years in the placebo group”

direct quote[Table 1]

“Median (IQR) body mass index: 26.1 (23.4-28.6) | 24.6 (21.7-27.8)”

The protocol was approved by the ethics committees of the Institute of Hematology and Blood Diseases Hospital (IIT2023068-EC-1). Written informed consent was obtained. The study was conducted in accordance with the Declaration of Helsinki.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approval and informed consent are adequately reported, with a named ethics committee and protocol number, and a statement of compliance with the Declaration of Helsinki.

Evidence

direct quote[Ethics statements]

“The trial protocol received approval from the ethics committees of the Institute of Hematology and Blood Diseases Hospital (IIT2023068-EC-1)”

direct quote[Methods, Participants]

“All patients provided written informed consent.”

direct quote[Ethics statements]

“and was conducted in strict accordance with the principles of the Declaration of Helsinki.”

PASSReviewer 2· 100% conf

Ethical approvals are clearly stated, with named IRB, informed consent, and adherence to the Declaration of Helsinki.

Evidence

direct quote[Ethics statements]

“The trial protocol received approval from the ethics committees of the Institute of Hematology and Blood Diseases Hospital (IIT2023068-EC-1)”

direct quote[Methods, Participants]

“All patients provided written informed consent.”

direct quote[Ethics statements]

“and was conducted in strict accordance with the principles of the Declaration of Helsinki.”

PASSReviewer 3· 100% conf

Ethical approval by a named ethics committee, informed consent, and regulatory compliance are all reported and adequate.

Evidence

direct quote[End of main text, Ethics statements]

“The trial protocol received approval from the ethics committees of the Institute of Hematology and Blood Diseases Hospital (IIT2023068-EC-1)”

direct quote[Methods, Participants]

“All patients provided written informed consent.”

direct quote[End of main text, Ethics statements]

“...and was conducted in strict accordance with the principles of the Declaration of Helsinki.”

The investigational product CM313 (and placebo) are identified, with supplier (Keymed Biosciences) and composition described. The placebo composition is provided. Statistical software (SAS version 9.4) and sample size software (PASS 2022) are identified with versions. No antibodies, cell lines, mycoplasma testing, or organisms are used in this clinical trial, so those sub-criteria are not applicable. All applicable sub-criteria (reagents_identified, software_tools_identified) are adequate.

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 (CM313) and placebo are identified, and statistical software is named with version. Other wet-lab resources are not applicable as this is a clinical trial without bench assays.

Evidence

direct quote[Methods, Procedures]

“CM313 or matching placebo was administered intravenously at a dose of 16 mg/kg weekly for eight weeks. The placebo contained the same excipient components as CM313 (histidine, histidine hydrochloride, arginine hydrochloride, and polysorbate 80) but without the active component.”

direct quote[Methods, Statistical analysis]

“Statistical analyses were conducted using SAS version 9.4.”

direct quote[Acknowledgments]

“We thank Keymed Biosciences for providing CM313 and placebo for this study”

PASSReviewer 2· 85% conf

Key resources are adequately identified: the investigational drug and software tools are described, and data code is provided.

Evidence

direct quote[Acknowledgments]

“We thank Keymed Biosciences for providing CM313 and placebo for this study”

direct quote[Methods, Statistical analysis]

“Statistical analyses were conducted using SAS version 9.4.”

PASSReviewer 3· 100% conf

The investigational product (CM313) and key reagents are adequately identified; software tools are specified with version and vendor.

Evidence

direct quote[Methods, Procedures]

direct quote[Methods, Statistical analysis]

“Sample size calculations were performed using PASS 2022 (NCSS Statistical Software). Statistical analyses were conducted using SAS version 9.4.”

direct quote[Acknowledgments]

“We thank Keymed Biosciences for providing CM313 and placebo for this study”

The paper names specific tests: Fisher's exact test for group comparisons, Miettinen-Nurminen method for CIs of differences, mixed-effects model for repeated measures, Kaplan-Meier method for time-to-event data, and Wilcoxon Mann-Whitney test for immune function changes. Exact p-values are reported (e.g., P<0.001, P=0.004). Confidence intervals are provided for differences. Statistical software is identified (SAS 9.4, PASS 2022). Data presentation includes per-group n, percentages, and Kaplan-Meier curves. As a clinical trial, assumptions_verified is considered adequate given the use of standard methods. Mathematical plausibility is not flagged as an issue; the reported percentages and counts are consistent.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical methods are well-described, including named tests, handling of missing data, and software identification. Exact p-values and confidence intervals are reported for primary and secondary outcomes.

Evidence

direct quote[Methods, Statistical analysis]

“Fisher’s exact test was used for group comparisons and the Miettinen-Nurminen method was used to calculate 95% CIs for differences between groups.”

direct quote[Results, Efficacy]

“difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001)”

direct quote[Methods, Statistical analysis]

“Statistical analyses were conducted using SAS version 9.4.”

PASSReviewer 2· 75% conf

Statistical methods are generally robust, but assumptions verification is not explicitly stated and some p-values are reported as thresholds.

Evidence

direct quote[Methods, Statistical analysis]

“Fisher’s exact test was used for group comparisons”

direct quote[Results, Efficacy]

“difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001)”

absence[Methods, Statistical analysis]

Assumptions not explicitly verified.

PASSReviewer 3· 90% conf

Statistical tests are named, exact p-values are reported, effect sizes with CIs are provided, software is identified, and data presentation is adequate. Mathematical plausibility checks are not applicable for these continuous outcomes.

Evidence

direct quote[Results, Efficacy, paragraph 1]

“difference 63.3% (95% confidence interval 33.7% to 81.3%; P<0.001)”

direct quote[Methods, Statistical analysis]

“Fisher’s exact test was used for group comparisons and the Miettinen-Nurminen method was used to calculate 95% CIs for differences between groups.”

direct quote[Table 2]

“CM313 group (n=30) | Placebo group (n=15) | Difference, % (95% CI) | P value”

The data availability statement provides a concrete route: a dataset DOI (10.57760/sciencedb.27748) and a URL (scidb.cn). Code is stated to be in the supplemental files. Repository deposit of raw patient data is not required for a clinical trial with privacy constraints, making that sub-criterion not applicable. The data accessibility route is concrete and adequate.

Sub-criteria

code sharingADEQUATE

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

A data availability statement is present with a repository link and DOI, but the code sharing statement is vague, referring only to 'supplemental files' without a permanent repository or version.

Evidence

direct quote[Data availability statement]

“Readers may access and download the dataset through https://www.scidb.cn/detail?dataSetId=3d08b314ed65413e82fd5015bd7c2677 or by using the advanced search function with the data doi: 10.57760/sciencedb.27748”

direct quote[Data availability statement]

“The code used to analyse the data in this paper can be found in the supplemental files.”

PASSReviewer 2· 90% conf

Data availability is excellent with a DOI and repository, and code is available in supplemental files.

Evidence

direct quote[Data availability statement]

“The code used to analyse the data in this paper can be found in the supplemental files.”

PASSReviewer 3· 95% conf

Data availability statement is present with a concrete dataset DOI; code is shared in supplemental files. Patient-level data not in a public repository is acceptable for a clinical trial.

Evidence

direct quote[Data availability statement]

“The code used to analyse the data in this paper can be found in the supplemental files.”

The trial is registered at ClinicalTrials.gov (NCT06199089). Methods are detailed enough for replication, including dosing, concomitant treatments, and outcome definitions. Limitations are explicitly discussed in a dedicated section, including small sample size, limited follow-up, single ethnic group, and single dosing regimen. Conclusions are proportional to the evidence, noting the need for further studies. Funding sources and a conflicts-of-interest statement are provided. A reporting guideline is not explicitly referenced, but the paper follows standard clinical trial reporting conventions.

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· 90% conf

The paper is well-reported with a trial registration number, detailed methods, limitations discussion, proportional conclusions, and funding/COI statements.

Evidence

direct quote[Abstract]

“Trial registration ClinicalTrials.gov NCT06199089”

direct quote[Discussion, Limitations of this study]

“This study has several limitations, including a small sample size, a limited follow-up period, and the lack of patient health related quality of life measurements.”

direct quote[Funding and Competing interests sections]

“Funding: This study received support from the Chinese Academy of Medical Sciences innovation fund for medical sciences... Competing interests: All authors have completed the ICMJE uniform disclosure form...”

PASSReviewer 2· 90% conf

Reporting is transparent with detailed methods, trial registration, and limitations discussion; however, a reporting guideline is not explicitly referenced.

Evidence

direct quote[Abstract and Methods]

“Trial registration ClinicalTrials.gov NCT06199089”

absence[Methods]

No explicit mention of CONSORT.

direct quote[Discussion, Limitations of this study]

“This study has several limitations, including a small sample size, a limited follow-up period, and the lack of patient health related quality of life measurements.”

PASSReviewer 3· 90% conf

Methods are complete, trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are declared. No reporting guideline checklist is mentioned, which is typical for a 2025 trial but noted as a minor gap.

Evidence

direct quote[Abstract]

“Trial registration ClinicalTrials.gov NCT06199089”

direct quote[Discussion, Limitations of this study]

“This study has several limitations, including a small sample size, a limited follow-up period, and the lack of patient health related quality of life measurements.”

direct quote[Funding and Competing interests sections]

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

Checked 40 references: 39 verified — 1 not checked.

Reproducibility

8 data/code links checked; 7 live, 1 dead.

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

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

Ready to submit after minor edits. The authors must deposit the analysis code in a public repository (e.g. GitHub, Zenodo) with a DOI and update the data availability statement. Additionally, referencing the CONSORT 2010 statement and reporting exact p-values for the primary outcome would strengthen the submission. The copyedit issues are minor but should be addressed for a polished manuscript.

1.
HIGHdata code
Deposit the analysis code in a public repository (e.g., Zenodo, GitHub) with a persistent DOI, then update the data availability statement to include the repository URL and DOI.
Supplemental files are not a version-controlled, permanent repository; reviewers and journals expect code to be accessible with a persistent identifier for full reproducibility.
2.
HIGHreporting
Add a statement in the Methods section (or at the end of the manuscript) that the trial adheres to the CONSORT 2010 statement for randomised trials, and consider submitting the CONSORT checklist as a supplementary file.
Explicitly referencing the reporting guideline is standard practice and is expected by clinical trial journals.
3.
MEDIUMstatistics
Report the exact p-value for the primary outcome (e.g., P=3.2×10^{-9}) instead of P<0.001, if the software can provide it.
Exact p-values allow readers to assess the evidence more precisely and are increasingly required by reporting guidelines.
4.
MEDIUMstatistics
Add a sentence in the Statistical Analysis section explicitly stating that assumptions for the mixed-effects model (e.g., normality, sphericity) were checked, or justify why the method is robust to violations.
Reviewers often request explicit assumption verification for parametric models to ensure the analysis is valid.
5.
MEDIUMcopyedit
In Table 1, change 'Include' to 'Includes' in the footnote to match the grammatical style of other footnotes.
Minor consistency issue flagged in the copyedit pass.
6.
MEDIUMcopyedit
In Results paragraph 1, rephrase the sentence about the patient who became pregnant to clarify that she successfully completed the study despite the pregnancy.
Clarity improvement to avoid ambiguous phrasing.
7.
MEDIUMcopyedit
Reformat Table 4 to ensure severity grade headers align clearly above the count columns, so the distribution for each adverse event is unambiguous.
The table layout may confuse readers when interpreting severity distributions.
8.
LOWreporting
In the Discussion, expand the limitation about cross-study comparisons by briefly stating how the differences in treatment regimens and definitions affect interpretation.
The paper already notes caution; adding specificity strengthens the limitations section.
9.
LOWother
Specify the exact version of the Declaration of Helsinki (e.g., 2013 version) in the ethics statement.
Minor precision improvement for regulatory compliance reporting.
10.
LOWreporting
Consider adding a brief statement about whether a data monitoring committee (DMC) was used.
Mentioning DMC oversight is a detail some clinical trial journals expect.

Full text (47,510 chars)Analyzed: Jul 7, 2026

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