Rigor Reviewed

Rigor-Reviewed Manuscript

BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.

Name: Adcurare Rigor Record — BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.
Item: BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.
Rating: 59
Author: Adcurare

Vu T, Durmus H, Rivner M, Shroff S, Ragole T, Myers B, Pasnoor M, Small G, Karam C, Vullaganti M, Peltier A, Sahagian G, Feinberg MH, Slanksy A, Barnett-Tapia C, Siddiqi Z, Gwathmey K, Badruddoja MA, Kamboh H, Ruggerie RN, Fedak RR, Stewart CA, Kurtoglu M, Kalayoglu M, Singer M, Jewell CM, Miljkovic MD, Dimachkie M, Mozaffar T, Howard JF Jr, MG-001 Study Team

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Adcurare Rigor Review — 4.25★ (Strong), 0 critical, 5 high issues for “BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.”

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Adcurare Editorial

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

Adcurare Rigor Review

Rigor Reviewed

4.25 / 5

Strong — minor issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

ReportingStudy design partially met−0.25★
ReportingStatistical analysis partially met−0.25★
ReportingData & code availability partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.6.0Source: full text

Problems surfaced3 types

Statistical reporting gaps (tests, assumptions, effect sizes)
Data/code availability incomplete
Study-design details incomplete (controls, blinding, power)

This Adcurare 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 phase 2b RCT of an mRNA CAR T cell therapy for myasthenia gravis, with strong scientific premise, ethical approvals, and transparent reporting. The main methodological weaknesses are the primary endpoint change, insufficient detail on key resources (reagent formulation, software versions), lack of statistical assumption verification, and incomplete data/code sharing.

Two of three independent reviewers agreed on most dimensions; the third (Reviewer 1) was more lenient on study design, key resources, statistical analysis, and data code availability. The synthesized judgments reflect the preponderance of evidence. Statistics verification recomputed 4 tests with full statistics; all were consistent. No retracted or not-found references were identified.

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

Recomputed 4 tests: 4 consistent, 0 inconsistent, 4 via agent-written checks.

Reporting

Eight Dimensions5 pass · 3 warn

The paper cites prior research establishing that MG is driven by autoantibodies from BCMA-positive plasma cells, discusses limitations of current treatments, and cites a prior open-label study of Descartes-08 to justify the trial. Strengths and weaknesses of prior work are acknowledged (e.g., limitations of conventional CAR T in autoimmune diseases, potential for infusion reactions). The rationale linking BCMA targeting to clinical improvement is logical.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established, citing prior work on MG immunopathology, BCMA as a target, and phase 1b/2a data for Descartes-08.

Evidence

paraphrase[Introduction, paragraphs 1-4]

“Paraphrase: The introduction summarizes MG pathology driven by BCMA-expressing plasma cells, limitations of conventional treatments, and prior phase 1b/2a data for Descartes-08.”

direct quote[Introduction, paragraph 3]

“While conventional BCMA-directed CAR T cell therapies—which rely on integrating lentiviral or gamma-retroviral vectors to encode the CAR—involve lymphodepletion chemotherapy that requires intensive postinfusion monitoring, with the potential for acute and delayed toxicity –, nonintegrating BCMA-directed CAR T cell therapies may circumvent this toxicity due to the lack of requirement for chemotherapy.”

direct quote[Introduction, paragraph 4]

“In an open-label, multicenter, phase 1b/2a trial of Descartes-08 in gMG (MG-001 parts 1 and 2), patients who received six once-weekly doses without preconditioning chemotherapy in an outpatient setting experienced a robust improvement in gMG symptom severity…The improvements persisted through 12 months of follow-up and were not associated with severe toxicity.”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific foundation for targeting BCMA-expressing plasma cells in MG, citing relevant prior research and the rationale for mRNA CAR T cell therapy.

Evidence

direct quote[Introduction, paragraph 2]

“The secretion of AChR autoantibodies is primarily driven by pathogenic B cell maturation antigen (BCMA)-expressing plasmablasts and long-lived plasma cells, and recent studies have suggested that BCMA may be an attractive therapeutic target in gMG.”

direct quote[Introduction, paragraph 3]

“Descartes-08 is an autologous BCMA-directed CAR T cell therapy that uses mRNA instead of an integrating viral vector to encode the CAR protein. This feature results in transient targeting and a well-defined pharmacokinetic profile without the risk of unchecked proliferation.”

paraphrase[Introduction, paragraph 2]

“The paper states that conventional treatments are often insufficient for complete symptom control and can result in considerable toxicity; newer targeted biologics still leave many patients with incomplete disease control requiring chronic immunosuppression.”

PASSReviewer 3· 95% conf

The paper clearly establishes the scientific premise, citing prior work on BCMA as a target in MG and the rationale for a non-integrating mRNA CAR T approach.

Evidence

direct quote[Introduction, paragraph 3]

“Descartes-08 is an autologous BCMA-directed CAR T cell therapy that uses mRNA instead of an integrating viral vector to encode the CAR protein.”

direct quote[Introduction, paragraph 2]

direct quote[Introduction, paragraph 3]

“Conventional treatments for gMG include chronic broad immunosuppression with corticosteroids and nonsteroidal immunosuppressive therapy; however, these are often insufficient for complete symptom control and can result in considerable toxicity due to off-target effects.”

Randomization was computer-generated with a permuted-block scheme, centrally assigned, and concealed. Blinding was maintained with opaque covers for infusion sets. A power analysis was performed (80% power to detect 47% difference), but only 26 (15/11) instead of the planned 30 participants comprised the primary efficacy population, reducing power. The primary endpoint was changed from MG-ADL to MGC at month 3 based on task force recommendations, which was disclosed but introduces a risk of bias. Inclusion/exclusion criteria were clearly defined. Pre-specified analysis was mITT. Outlier handling not explicitly described. No independent replication cohort, but this is understandable for a phase 2b trial. Sub-criteria: randomization_method adequate, randomization_unit adequate, blinding_levels adequate, power_analysis reported_but_inadequate (due to unmet sample size and endpoint change), inclusion_exclusion adequate, outlier_handling not_reported, controls (placebo) adequate, replicate_distinction and independent_replication not_applicable for a human RCT.

Sub-criteria

controlsADEQUATE

power analysisINADEQUATE

blinding levelsADEQUATE

outlier handlingNOT REPORTED

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 rigorous for a phase 2b trial: randomized, double-blind, placebo-controlled with a clear primary endpoint and pre-specified analysis. Several design sub-criteria are not applicable per the human RCT applicability guide.

Evidence

direct quote[Methods (Trial design)]

“Randomization was performed centrally using a computer-generated permuted-block scheme without stratification. Block sizes were varied and concealed from site personnel to maintain unpredictability in allocation.”

direct quote[Methods (Trial design)]

“Blinding of study personnel, clinic staff and participants during infusion was maintained using opaque coverings for the infusion bag and tubing, which were identical between Descartes-08 and placebo.”

direct quote[Methods (Statistical analysis)]

“We estimated that 15 participants per treatment group would provide 80% power to detect a difference of 47% in responders between Descartes-08 and placebo.”

WARNReviewer 2· 85% conf

The trial is well-designed (randomized, double-blind, placebo-controlled) with a clear randomization method and blinding procedures, but the power analysis assumptions were partly unmet (fewer participants than planned in the primary efficacy population), and there was a change in the primary endpoint during the trial.

Evidence

direct quote[Methods, Trial design, paragraph 1]

direct quote[Methods, Statistical analysis, paragraph 1]

“We estimated that 15 participants per treatment group would provide 80% power to detect a difference of 47% in responders between Descartes-08 and placebo.”

direct quote[Results, Participant characteristics, paragraph 1]

“On January 8, 2024, after the enrollment of 44 participants and before the unblinding of data and database lock, the steering committee of the trial, in consensus with the study monitoring committee, decided to implement a change in the primary outcome: from the MG-ADL score to the MGC score (previously a secondary outcome).”

WARNReviewer 3· 85% conf

The design is well-described for a human RCT with randomization, blinding, and a pre-specified analysis, but lacks pre-specification of the primary endpoint change before data unblinding raises concern. Several elements are not applicable to a human RCT.

Evidence

direct quote[Methods: Trial design]

“Randomization was performed centrally using a computer-generated permuted-block scheme without stratification.”

direct quote[Methods: Trial design]

direct quote[Results: Participant characteristics]

Sex is reported (66.7% female in Descartes-08, 54.5% in placebo) and is mixed so justification for single-sex not needed. Age and weight are reported as means. Comorbidities are not listed individually but health status via inclusion criteria is described. Species/strain and housing not applicable for a human study. Demographics table includes age, sex, ethnicity, disease duration, antibody status. Sub-criteria: sex_reported adequate, sex_justified not_applicable, age_weight_health adequate, demographics adequate, species_strain_source not_applicable, housing_conditions not_applicable.

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· 85% conf

The paper adequately reports sex, age, weight, disease duration, antibody status, and other demographics. For a human RCT, species/strain/housing are not applicable, and sex justification is not required since both sexes were enrolled.

Evidence

direct quote[Table 1]

“Sex, n (%) | Female 10 (66.7) | 6 (54.5) | 16 (61.5) | Male 5 (33.3) | 5 (45.5) | 10 (38.5)”

direct quote[Table 1]

“Mean age, years (s.d.) | 56.7 (16.39) | 59.0 (13.96) | 57.7 (15.16)”

direct quote[Table 1]

“MGFA class at screening, n (%) | IIa 0 | 2 (18.2) | 2 (7.7) …”

PASSReviewer 2· 95% conf

Baseline demographics including age, sex, weight, ethnicity, MGFA class, autoantibody status, and disease duration are reported in a table; key biological variables are adequately described.

Evidence

direct quote[Table 1]

“Mean age, years (s.d.) | 56.7 (16.39) | 59.0 (13.96) | 57.7 (15.16) | Sex, n (%) | Female 10 (66.7) | Male 5 (33.3)”

direct quote[Table 1]

“Anti-AChR | 11 (73.3) | 8 (72.7) | 19 (73.1)”

direct quote[Results, Participant characteristics, paragraph 2]

“Mean weight, kg (s.d.) | 93.83 (20.001) | 105.37 (27.496) | Median duration of disease, years (range) | 5.5 (2–23) | 10 (4–26)”

PASSReviewer 3· 95% conf

Key human biological variables (sex, age, weight, autoantibody status, MGFA class) are reported in demographics. The trial enrolled both sexes but sex-justification is not applicable as the study is designed to include both sexes.

Evidence

direct quote[Table 1]

“Sex, n (%) | Female | 10 (66.7) | 6 (54.5) | 16 (61.5) | Male | 5 (33.3) | 5 (45.5) | 10 (38.5)”

direct quote[Table 1]

“MG antibody status, n (%) | Anti-AChR | 11 (73.3) | 8 (72.7) | 19 (73.1)”

The trial was approved by central and local IRBs (WCG IRB, ethics committees at University of Toronto, University of Alberta, Istanbul University) and a named regulatory authority. Written informed consent was obtained from all participants. Compliance with the Declaration of Helsinki and ICH E6 GCP guidelines is stated. Sub-criteria: irb_ethics_statement adequate, informed_consent adequate, regulatory_compliance adequate, iacuc_statement not_applicable.

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 approvals are reported with named IRBs/ethics committees and informed consent, along with regulatory compliance statements.

Evidence

direct quote[Methods (Oversight)]

“The trial was approved by regulatory authorities in each country (USA, Canada and Türkiye), the central and local institutional review boards in the USA (Western Institutional Review Board-Copernicus Group, WCG IRB, Puyallup, WA), and the ethics committee at each site in other countries (the research ethics boards at the University of Toronto and the University of Alberta, as well as the ethics committee at Istanbul University).”

direct quote[Methods (Oversight)]

“All participants provided written informed consent before any study-related activities.”

direct quote[Methods (Oversight)]

“The MG-001 part 3 trial was performed in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonization E6 guidelines for Good Clinical Practice.”

PASSReviewer 2· 100% conf

Ethics committee approval and informed consent are clearly stated, with named IRBs and compliance with the Declaration of Helsinki and Good Clinical Practice.

Evidence

direct quote[Methods, Oversight, paragraph 1]

“All participants provided written informed consent before any study-related activities.”

direct quote[Methods, Oversight, paragraph 1]

“The MG-001 part 3 trial was performed in accordance with the principles of the Declaration of Helsinki and the International Council for Harmonization E6 guidelines for Good Clinical Practice.”

PASSReviewer 3· 98% conf

Ethics approval from named IRBs/ethics committees, informed consent, and regulatory compliance (Declaration of Helsinki, GCP) are explicitly stated.

Evidence

direct quote[Methods: Oversight]

“All participants provided written informed consent before any study-related activities.”

The investigational product is autologous BCMA-directed mRNA CAR T cells, manufactured under GMP; dose is given as 52.5 × 10^6 viable CAR+ cells per kg ±45%. Placebo is 'acellular placebo lot' matched in appearance. Cytokine analysis used S-PLEX, V-PLEX panels from Meso Scale Discovery. Statistical software: SAS version 9.2 or higher, Mathematica version 11.0 or higher. No antibodies, cell lines, or organisms are used in this human clinical trial; those criteria are n/a. Mycoplasma testing is n/a. Reagents_identified is reported adequately for the investigational product and cytokine panels.

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· 70% conf

The investigational product (Descartes-08) is named with manufacturer and dose; placebo matching is described; software tools are identified; cell line/antibody/mycoplasma criteria are not applicable for this human clinical trial without wet-lab assays. Reporting is adequate for a clinical drug trial.

Evidence

direct quote[Abstract, Methods (Trial design)]

“Descartes-08 is an autologous BCMA-directed mRNA chimeric antigen receptor T cell therapy.”

direct quote[Methods (Trial design)]

“The dose of Descartes-08 was 52.5 × 10 6 viable CAR + cells per kg ± 45% per infusion, which was the dose tested in the phase 2a study.”

direct quote[Methods (Statistical analysis)]

“Statistical analyses were conducted using SAS (version 9.2 or higher) and Mathematica (version 11.0 or higher), where applicable.”

WARNReviewer 2· 70% conf

The investigational product (Descartes-08) is described along with dose and manufacturing, but specific catalog numbers, kits, and software versions (beyond vague references) are not consistently provided.

Evidence

direct quote[Methods, Trial design, paragraph 2]

“The dose of Descartes-08 was 52.5 × 10^6 viable CAR+ cells per kg ± 45% per infusion, which was the dose tested in the phase 2a study.”

direct quote[Methods, Statistical analysis, paragraph 2]

“Statistical analyses were conducted using SAS (version 9.2 or higher) and Mathematica (version 11.0 or higher), where applicable.”

direct quote[Methods, Trial design, paragraph 1]

“The placebo was matched to Descartes-08 in appearance and supplied in identical containers.”

PASSReviewer 3· 90% conf

The investigational product (Descartes-08) and placebo are described with dose and manufacturing details. Reagents for cytokine analysis are identified by vendor and panel. Software (SAS, Mathematica) versions are given.

Evidence

direct quote[Methods: Trial design]

“The dose of Descartes-08 was 52.5 × 10 6 viable CAR + cells per kg ± 45% per infusion, which was the dose tested in the phase 2a study.”

direct quote[Methods: Endpoints]

“Serum samples collected during noninfusion visits (screening day, day 57, day 85) and preinfusion visits (day 1, day 29) were analyzed using the Meso Scale Discovery platform...”

direct quote[Methods: Statistical analysis]

“Statistical analyses were conducted using SAS (version 9.2 or higher) and Mathematica (version 11.0 or higher), where applicable.”

Primary endpoint uses a two-sample proportion test (Wald chi-squared); test is named. Assumptions of the test (independence, expected frequencies) are plausible but no verification of model fit is reported. Exact p-values: P = 0.0472 and P = 0.0258 are reported. Effect sizes: difference in proportions with 95% CI is reported for the primary outcome (0.39, 95% CI 0.01–0.77). Software identified (SAS, Mathematica). Data presentation: figures show means with 95% CI, individual data points are not shown for small n (n=15,11) which would be desirable. Mathematical plausibility: no obvious errors in the primary analysis, but some percentages in subgroups have small denominators where rounding could be checked but no arithmetic impossibility is apparent. Sub-criteria: tests_named adequate, assumptions_verified not_reported, exact_p_values reported_but_inadequate (only two p-values, most other comparisons not formally tested as secondary), effect_sizes_ci adequate for primary, software_identified adequate, data_presentation reported_but_inadequate (no individual points, bar-only), mathematical_plausibility pass.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciADEQUATE

data presentationINADEQUATE

software identifiedADEQUATE

assumptions verifiedNOT REPORTED

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, exact p-values are reported, effect sizes and CIs are provided, software is identified, data presentation includes per-group Ns and missing data handling. Assumptions verification is handled implicitly through prespecified analysis methods (appropriate for a clinical trial). Mathematical plausibility checks are not applicable for continuous outcomes with small N.

Evidence

direct quote[Results, Table 2]

“P = 0.0472”

direct quote[Table 2]

“Difference in proportions (95% CI) | 0.39 (0.01–0.77)”

direct quote[Methods (Statistical analysis)]

“Statistical significance was determined using a two-sided two-independent-sample proportion test.”

WARNReviewer 2· 85% conf

Statistical tests are named, power analysis is given, and exact p-values are reported for the primary endpoint. However, test assumptions (normality, homoscedasticity) are not verified, effect sizes with confidence intervals are only partially provided, and data presentation in figures uses means/CIs but individual data points are not shown for small groups.

Evidence

direct quote[Methods, Statistical analysis, paragraph 2]

“the response status at month 3 ... was analyzed using a two-independent-sample proportion test at a two-sided 5% significance level; a Wald chi-squared test was used”

direct quote[Results, Primary outcome]

“66.7% (n=10/15) versus 27.3% (n=3/11), P = 0.0472”

direct quote[Table 2]

“Difference in proportions (95% CI) | 0.39 (0.01–0.77)”

WARNReviewer 3· 80% conf

Statistical tests are named and the power analysis is reported, but exact p-values are often given as thresholds ('P = 0.0472', 'P = 0.0258') which is acceptable. However, key secondary outcomes were not formally tested due to hierarchical testing limitations, and effect sizes with CIs are reported only for the primary endpoint. Assumptions verification is not explicitly addressed, but the methods used (proportion test) are standard. The primary analysis uses a modified ITT population, which is acceptable.

Evidence

direct quote[Results: Primary outcome]

“At month 3, there were significantly more MGC responders (≥5-point score reduction) in the Descartes-08 group compared to the placebo group in the overall population (66.7% versus 27.3%, P = 0.0472)”

direct quote[Table 2]

“Difference in proportions (95% CI) | 0.39 (0.01–0.77)”

direct quote[Methods: Statistical analysis]

“Statistical analyses were conducted using SAS (version 9.2 or higher) and Mathematica (version 11.0 or higher), where applicable.”

The data availability statement says: 'Access to anonymized trial-level data (analysis datasets) and/or the study protocol will be provided upon request to qualified researchers conducting independent, rigorous research, after the review and approval of a research proposal and statistical analysis plan, as well as the execution of a data sharing agreement.' This meets the minimal threshold but is vague (no platform, no timeline beyond '12 months'). No repository deposit or accession numbers are provided; the statement is managed access for patient-level data, which is standard but not fully adequate per the scoring criteria. Code sharing is not mentioned.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositNOT REPORTED

data availability statementINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

A data availability statement is provided with a concrete access mechanism via a named data-sharing process, representing adequate reporting for a clinical trial with patient-level data. Code sharing is not applicable as no bespoke code is mentioned.

Evidence

direct quote[Data availability section]

“Access to anonymized trial-level data (analysis datasets) and/or the study protocol will be provided upon request to qualified researchers conducting independent, rigorous research, after the review and approval of a research proposal and statistical analysis plan, as well as the execution of a data sharing agreement. Data requests can be submitted at any time and will be responded to within 30 business days of submission. The data will be accessible for 12 months. Requests can be submitted to trials@cartesiantx.com.”

WARNReviewer 2· 75% conf

A data availability statement is present describing a managed-access process, but no repository deposit or accession numbers are provided, and code sharing is not mentioned.

Evidence

direct quote[Data availability section]

absence[Entire paper]

No code sharing is mentioned.

absence[Data availability section]

No repository deposit is reported.

WARNReviewer 3· 90% conf

A data availability statement is present, but the access route is vague ('upon request' to trials@cartesiantx.com with a research proposal), which is inadequate. No data repository deposit or accession numbers are provided (controlled access is acceptable for patient data, but the mechanism is not clearly defined). Code sharing is not addressed.

Evidence

direct quote[Data availability section]

absence[Data availability and Code availability sections]

No repository deposit or code sharing is mentioned.

Methods detail the trial design, randomization, blinding, endpoints, and statistical analysis. Trial registration number is provided (NCT04146051). A CONSORT flow diagram (Figure 1) is provided; the paper references a 'Reporting Summary' linked to the online content, which fulfills the reporting guideline requirement. All pre-specified outcomes appear reported (primary and secondary endpoints, safety, post hoc analyses). Limitations are discussed in detail (small sample, imbalances, seronegative overrepresentation, potential unblinding due to IRRs, etc.). Conclusions are proportional: the paper uses cautious language (e.g., 'may be achievable', 'preliminary data') and does not overclaim. Funding sources (Cartesian Therapeutics, NIH grants) and competing interests are fully disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Reporting is comprehensive: methods are detailed, the trial is registered (NCT04146051), a CONSORT-like diagram is provided, limitations are discussed, conclusions are proportional, and funding/COI statements are present. A reporting guideline is not explicitly named but a CONSORT diagram is present, meeting the spirit. The primary endpoint change is transparently described.

Evidence

direct quote[Abstract, Methods]

“ClinicalTrials.gov identifier: NCT04146051”

direct quote[Results, Figure 1 legend]

“Fig. 1 CONSORT diagram for the MG-001 part 3 study.”

paraphrase[Discussion, paragraphs 10-12]

“Paraphrase: The discussion lists limitations: small sample size, imbalances in disease characteristics, overrepresentation of triple seronegative patients, potential unblinding due to IRRs, and protocol-mandated stable dosing that limited assessment of drug-free remission.”

PASSReviewer 2· 90% conf

Methods are detailed for replication, the trial is registered (NCT04146051), limitations are discussed, conclusions are proportional, and funding/COI statements are provided. Reporting guideline submission is mentioned via a linked reporting summary.

Evidence

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT04146051”

direct quote[Discussion, paragraph 5]

“There are several important limitations to note. First, although randomized and placebo-controlled, this was a phase 2 study with a limited sample size...”

direct quote[Acknowledgements; Competing interests]

“This work was supported by Cartesian Therapeutics, which provided the study product and was involved in the design, execution and analysis of the study.”

PASSReviewer 3· 90% conf

The Methods are detailed enough for replication. The trial is registered (NCT04146051). A reporting guideline is not explicitly named (although a CONSORT diagram is provided). Limitations are discussed. Conclusions are proportional. Funding and COI are stated.

Evidence

direct quote[Abstract and Results]

“ClinicalTrials.gov identifier: NCT04146051”

direct quote[Discussion]

“There are several important limitations to note. First, although randomized and placebo-controlled, this was a phase 2 study with a limited sample size and modest power (80%) to detect differences in the primary outcome, making any comparisons in secondary outcomes purely descriptive.”

direct quote[Acknowledgements and Competing interests]

“This work was supported by Cartesian Therapeutics, which provided the study product and was involved in the design, execution and analysis of the study.”

5 copyedit issues flagged: mostly consistency, other.

Checked 67 references: 66 verified — 1 not checked.

Reproducibility

3 data/code links checked; 3 live.

Registered (3 IDs: ClinicalTrials.gov). Reporting guideline cited: CONSORT.

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after minor-to-moderate edits. The primary endpoint change must be thoroughly justified, key resource descriptions should be expanded, statistical assumptions should be verified, and data/code sharing details need to be improved. The copyedit issues are minor but should be fixed.

1.
HIGHreporting
In the Results section, add a clear rationale for the primary endpoint change (MG-ADL to MGC), including a reference to the published task force recommendation and a justification that the change was made before unblinding.
2.
HIGHdata code
Add a code-sharing statement to the Data availability section, depositing SAS/Mathematica code used for the primary analysis in a public repository (e.g., GitHub) with a DOI.
3.
HIGHdata code
Deposit the anonymized trial-level data (analysis datasets) in a recognized repository (e.g., ClinicalTrials.gov results database, Vivli, or an institutional repository) instead of relying solely on email-based managed access.
4.
HIGHstatistics
In the Methods (Statistical analysis), add a statement verifying that the test assumptions for the primary analysis (independence, expected frequencies >5 for chi-square) were checked and met.
5.
HIGHrigor
In Table 1 or the Methods, provide the exact formulation of Descartes-08 (e.g., excipients, storage buffer) and the composition of the placebo.
6.
MEDIUMreporting
Add explicit version numbers and RRIDs for SAS and Mathematica in the Methods (Statistical analysis), replacing the vague 'version 9.2 or higher' range.
7.
MEDIUMstatistics
For each secondary outcome reported as a mean change, provide the 95% confidence interval or a p-value (if formally tested), or state that these are descriptive only.
8.
MEDIUMreporting
In the Discussion, add a sentence explicitly discussing the potential impact of the primary endpoint change on the interpretation of results.
9.
MEDIUMreporting
In the Methods (Statistical analysis), report exact p-values for all results shown as significant, not just the primary endpoint and one subgroup.
10.
MEDIUMrigor
In Figure 2, add individual data points (dot plots) alongside the mean/CI bars for the primary outcome to enhance transparency about distributions.
11.
LOWcopyedit
In Results, paragraph 1, add a comma after 'database lock' for clarity in the sentence describing the primary endpoint change.
12.
LOWcopyedit
In Extended Data Table 5 caption, remove the double comma: change 'limited , , including' to 'limited, including'.
13.
LOWcopyedit
In the Methods (Statistical analysis), expand the SAS procedure names (PROC MI, PROC MIANALYZE) at first use.
14.
LOWreporting
Explicitly state adherence to the CONSORT 2010 checklist for RCTs in the Methods or Reporting summary.

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BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial.

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DOI

10.1038/s41591-025-04171-y

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