COVID Action Alert: Advocates speak out on human challenge trials

July 21, 2020

Welcome to the first in a periodic series of “COVID Action Alerts” from AVAC—these alerts are for HIV advocates whose expertise, interests, skills and voices are needed to influence and expedite an ethical, equitable and effective COVID-19 pandemic response. To start, we highlight emergent vaccine trial design issues, and the need to learn from history and apply best practices as the search for a COVID-19 vaccine proceeds with unprecedented speed. This week, a team at Oxford University announced safety data from a Phase I/II trial of its chimp adenovirus candidate that’s also in efficacy trials; next week Moderna is scheduled to begin enrolling 30,000 volunteers in a trial of its mRNA vaccine candidate.

Speed is essential, but not at the expense of cutting corners with ethics, safety, equity, access, peer review, and active, authentic engagement. And HIV vaccine advocates have a critical role to play in guiding the conversation.

One issue we are tracking is the ethics of and community perspectives on “human challenge experiments”. Click here to read and consider a sign-on statement on this issue, co-authored by AVAC and TAG, and read on for more information.

The Oxford University team just released safety data from an ongoing Phase I/II trial of a COVID-19 vaccine candidate. The trial found that the vaccine candidate, which is already in Phase II/III trials in Brazil, South Africa and the UK, was generally safe and that it induced both cellular and humoral immune responses. This trial team is one of many working to find an effective vaccine with all possible speed, and this vaccine candidate is one that is being considered for large-scale, randomized, controlled efficacy trials in the new NIH-funded COVID Prevention Trials Network (CoVPN). At the same time, one of the options the Oxford team is discussing is a human challenge trial—a proposed design that has received backing from more than a thousand scientists and researchers.

As background, challenge trials involve deliberate exposure to a pathogen in order to test vaccines. Typically, they involve pathogens for which treatments are available (malaria challenge studies are probably the best-known example).

AVAC feels that a human challenge with SARS-CoV-2 is not justified given the lack of effective treatments and the poorly understood potential consequences of infection, even in young people. Given the current state of the pandemic, which makes traditional, blinded, placebo-controlled efficacy trials quite feasible, it is not clear that challenge trials would speed the development of a safe and effective COVID-19 vaccine. In order to conduct a challenge study, the trialists would need to develop a stock of standardized virus—a process that could take months. Controlled human infection studies might contribute to vaccine development, but they will not automatically accelerate SARS-CoV-2 vaccine development timelines.

AVAC, TAG and its partners have spent more than two decades tracking trial design issues as they impact people at the epicenter of pandemics, who are also often neglected by the health systems that are supposed to serve them. AVAC and TAG issued a joint statement in May, when the idea of human challenge trials was first proposed in a WHO document, and further drafted guiding principles for choosing a challenge study design.

Now, AVAC and TAG have developed this sign-on statement to provide an expanding group of advocates and activists with a shared platform for articulating priorities and concerns. We hope you’ll add your name and/or organization.

The sign-on statement is just one part of our approach to ensuring HIV expertise and advocacy experience is brought to bear on this new pandemic. And the development of a challenge model, and the debates around them, should not delay the urgency of well-designed clinical trials and robust stakeholder engagement throughout the process.

Next week, a large efficacy trial of a vaccine candidate developed by Moderna (mRNA-1273) is scheduled to begin enrolling 30,000 volunteers in collaboration with the CoVPN. The CoVPN is also collaborating with AstraZeneca, Janssen, Novavax and Sanofi, each of which is expected to begin enrolling 30,000-person Phase III vaccine trials by the end of this year. Each of these trials uses a traditional design, not a human-challenge approach. Community engagement to ensure support for and access to the results of research are essential.

As such, AVAC, TAG and ITPC have launched a global COVID Advocates Advisory Board, which brings years of research engagement best practices to the context and considerations of COVID-19 research and development—-an area that evolves every day. And with the first of five 30,000-person efficacy trials beginning next week, we need a CAAB now, more than ever.

Are you in a community where trials are ongoing, or proposed? If you’d like additional information, background or advocacy support in learning more or gathering views, please let us know!