In a major development, Moderna has posted an updated protocol for its Phase 3 study of the Moderna COVID-19 Vaccine on December 23.
The protocol reflects inclusion of Amendment 6 from Dec. 23, 2020.
What is in it?
The purpose of this amendment is to inform all ongoing study participants of the availability of and eligibility criteria of any COVID-19 vaccine made available under an Emergency Use Authorization (EUA) and to offer participants who originally received placebo in this study the potential benefit of vaccination against COVID-19, given that the primary efficacy endpoint for the Moderna COVID-19 Vaccine was met per the protocol-defined interim analysis.
Safety
Safety and reactogenicity will be assessed by clinical review of all relevant parameters including solicited ARs (local and systemic events), unsolicited AEs, SAEs, MAAEs, AEs leading to discontinuation, abnormal vital signs, and physical examination findings.
All safety analyses will be based on the Safety Set, except summaries of solicited ARs, which will be based on the Solicited Safety Set. All safety analyses will be provided by treatment group, and by treatment cohort as applicable, unless otherwise specified
The number and percentage of participants with any solicited local AR, with any solicited systemic AR, and with any solicited AR during the 7-day follow-up period after each injection will be provided (Part A, the Blinded Phase only).
A 2-sided 95% exact CI using the Clopper-Pearson method will be also provided for the percentage of participants with any solicited AR for each treatment group.
The number and percentage of participants with solicited ARs, unsolicited AEs, SAEs, MAAEs, Grade 3 or higher ARs and AEs, and
AEs leading to discontinuation from study vaccine or participation in the study will be summarized. Unsolicited AE will be presented by MedDRA preferred term and system organ class.
For all other safety parameters, descriptive summary statistics will be provided.
Further details will be described in the statistical analysis plan (SAP).
Immunogenicity:
The secondary immunogenicity endpoints will be analyzed using the Immunogenicity Subset by treatment group, by treatment cohort as applicable, and by baseline SARS-CoV-2 serostatus, unless otherwise specified.
The SAP will describe the complete set of immunogenicity analyses, including the approach to sample individuals into an Immunogenicity Subset for characterizing vaccine immunogenicity and assessing immunological correlates of risk and protection.
Data from quantitative immunogenicity assays will be summarized for each treatment group using positive response rates and geometric means with 95% confidence intervals, for each timepoint for which an assessment is performed.
Data from qualitative (ie, yielding a positive or negative result) assays will be summarized by tabulating the frequency of positive responses for each assay by group at each timepoint that an assessment is performed.
Analyses will focus on the
2 key immunogenicity time points and the change in marker response between them:
Day 1 before the first dose of IP and Day 57 (28 days after the second dose of IP).
The SAP will describe the complete set of immunogenicity analyses.
Quantitative levels or geometric mean titer (GMT) of specific bAb with corresponding 95% CI at each timepoint and geometric mean fold rise (GMFR) of specific bAb with corresponding 95% CI at each
post-baseline time point over the pre-dose baseline at Day 1 will be provided by the study arm.
Descriptive summary statistics including median, minimum, and maximum will also be provided.
GMT of specific nAb with corresponding 95% CI at each timepoint and GMFR of specific nAb with corresponding 95% CI at each post-baseline time point over pre-dose baseline at Day 1 will be provided by the study arm.
Descriptive summary statistics including median, minimum, and maximum will also be provided.
For summarizations of group variables values, antibody values reported as below the LOD or LLOQ will be replaced by 0.5 × LOD or 0.5 × LLOQ. Values that are greater than the upper limit of quantification (ULOQ) will be converted to the ULOQ.
The number and percentage of participants with a fold rise ≥ 2, ≥ 3, and ≥ 4 of serum SARS-CoV-2-specific nAb titers and participants with seroconversion due to vaccination from baseline will be provided with 2-sided 95% CI using the Clopper-Pearson method at each post-baseline time point.
Seroconversion due to vaccination at a participant level is defined as a change from below the LOD or LLOQ to equal or above LOD or LLOQ, or at least a 4-fold rise in terms of neutralizing antibody or vaccine antigen-specific binding antibody in participants with pre-existing bAb or nAb.
The GMT of specific nAb for each group and the geometric mean ratio (GMR) of mRNA-1273 versus placebo with corresponding 2-sided 95% CI will be estimated at each study time point using an analysis of covariance (ANCOVA) model with the treatment group and baseline values, if applicable, as explanatory variables, the analysis may adjust for the stratification factor.
Study Flow Diagram: Part A, the Blinded Phase followed by Part B, the Open-Label Observational Phase
Part B, the Open-Label Observational Phase
Did you subscribe to our daily newsletter?
It’s Free! Click here to Subscribe!
Source: Moderna
