CoVPN 3008 - Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern

Fred Hutchinson Cancer Center, Seattle WA

Investigators

Linked publications & trials

Abstract

Project Abstract This proposal outlines the scientific agenda for the COVID-19 Prevention Network (CoVPN) Vaccines Leadership Operations Center (LOC) for implementation of the COVID-19 vaccine efficacy trial, CoVPN 3008 (the Ubuntu study) entitled “Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS- CoV-2 Variants of Concern.” As the global COVID-19 pandemic has persisted, it has become clear not only that there are great risks faced by people who are immunocompromised, but also that there is an urgent need to better understand infection and disease in these populations so we can prevent severe COVID-19 as well as chronic SARS-CoV-2 infections that could promote transmission and the emergence of new, dangerous variants. This is particularly true for the over 37 million people living with HIV (PLWH) who are concentrated in sub-Saharan Africa and have been significantly underrepresented in COVID-19 vaccine trials. This novel study aims to address critical knowledge gaps by evaluating COVID-19 mRNA vaccine efficacy among PLWH, including the influence of prior infection and degree of immunocompromise. This multicenter trial comparing different regimens of the Moderna mRNA-1273 and mRNA-1273.222 vaccines will test the efficacy of the vaccines in preventing COVID-19 disease regardless of severity, and in preventing COVID-19 severe disease, in people who are at risk for symptomatic and severe COVID-19 in areas of the world where the prevalence of SARS-CoV-2 Variants of Concern is substantial. This is the first large scale study evaluating the effectiveness of mRNA vaccines against symptomatic and severe COVID-19 among PLWH. In this study, at Month 0 (enrollment) all participants will receive a 100-mcg dose of mRNA-1273. At Month 1, all participants without evidence of prior SARS-CoV-2 infection at baseline (based on serology) will receive a second dose of mRNA-1273. At Month 6, all participants (regardless of baseline SARS- CoV-2 status) will receive a 100-mcg dose of either mRNA-1273 or mRNA-1273.222, depending on their randomization at enrollment. All trial endpoint assays will be done using qualified and validated assays for diagnosis and immune monitoring. The follow up of this study is divided into two stages: Pre-Month 6 stage (visits up to and including Month 6) and post-Month 6 stage (visits through to Month 12). This allows a timely evaluation of the pre-Month 6 study objectives as soon as Month 6 diagnostic data are available without the need to wait until the end of Month 12 follow up. Specific aims of this study pertaining to both pre- and post-Month 6 stages are to assess the relative risk of symptomatic and severe COVID-19 after the first vaccine dose at Month 0 through to Month 6 in PLWH who are SARS-CoV-2 negative at baseline who receive a 2-dose mRNA-1273 vaccine regimen vs. in PLWH who are SARS-CoV-2 positive at baseline who receive a 1-dose mRNA-1273 regimen, as well as to assess this relative risk for complete follow-up through to Month 12. Specific aims of this study pertaining to the post-Month 6 stage are to assess the relative risk of symptomatic and severe COVID-19 after the Month 6 dose through to Month 12 among those who received mRNA-1273 at Month 6 vs. those who received mRNA-1273.222 at Month 6. Additionally, this study will assess safety and tolerability of mRNA-1273 and mRNA-1273.222 in PLWH and adults who are at risk of severe COVID-19 in both the pre-Month 6 and post-Month 6 stages. The study will also seek to characterize SARS-CoV-2 nucleic acid amplification test (NAAT) persistence, viral shedding and the evolution of viral mutations among participants who acquire SARS-CoV-2 infection. By collecting efficacy and safety data in over half-a-dozen countries across sub-Saharan Africa, the study team hopes to inform regulators in the region and help facilitate access to mRNA vaccine technology across Africa. Importantly, the study will also assess both cellular and antibody immune correlates of protection against symptomatic COVID-19 and other outcomes.