Hepatitis C Human Challenge Studies

1Day Sooner, a nonprofit advocacy group for healthy medical volunteers, is working with researchers to realize proposed human challenge studies for hepatitis C. In a human challenge study, adult volunteers are deliberately infected with a disease. This is usually done to test a new vaccine or treatment.

Hepatitis C Basics

Hepatitis C is a liver infection caused by the hepatitis C virus (HCV). HCV is a blood-borne virus, primarily transmitted through shared needles or other sharp instruments with blood on them (even microscopic amounts). It’s treatable, but there is no vaccine. Tens of millions of people around the world have hepatitis C, and most don’t know it — it causes damage to the liver slowly, usually over decades, but for most people there aren’t other noticeable symptoms.

1Day Sooner and many other experts believe that challenge studies will be necessary to develop a hepatitis C vaccine in the foreseeable future, and that they can be conducted safely and ethically. Proposals for hepatitis C challenge studies are being prepared in Canada, the US, and the UK, and we anticipate at least one study to begin recruitment by early 2024.

Today, human challenge studies place participant safety and consent at the forefront. A systematic review of published human challenge studies from 1980 to 2021 found no recorded deaths among over 200 individual trials involving a total of over 15,000 people. There were 24 “severe adverse events” recorded, many of which were precautionary hospital stays (Adams-Phipps et al., 2023).

While no medical study is risk-free, any hepatitis C studies will involve extensive oversight and volunteers will be rigorously informed of risks and the purpose of a study, ensuring they can be done ethically.

Why Use A Challenge Study For Hepatitis C?

For an in-depth, academic examination of hepatitis C challenge studies and related scientific and ethical questions, see the supplement to Clinical Infectious Diseases dedicated to the topic, published in August 2023.

Even though treatment for hepatitis C is effective, in the last ten years, the number of total infections worldwide has barely budged — but with a vaccine and treatments, there’d be a way to one day wipe out hepatitis C for good.

Still, hepatitis C vaccines have not been a major priority in part because it is so difficult to test them. People who inject drugs (PWIDs) are the only population with sufficiently high transmission rates to enable early vaccine efficacy studies. These studies require major harm reduction interventions that protect the PWID participants, but also slow the pace by reducing natural hepatitis C infection rates needed to determine efficacy. The most recent hepatitis C vaccine study among PWIDs took six years to complete, ending in 2018 (Page et al., 2021). There hasn’t been another one started since then.

Challenge studies can provide quick results using a fraction of the volunteers in a fraction of the time. That is why numerous researchers — including signatories to 1Day Sooner’s open letter — believe challenge studies are the only realistic option to develop a hepatitis C vaccine, especially considering the lack of suitable animal models (Liang, Feld, Cox & Rice, 2021). Volunteers, likely up to one hundred for a trial of a single vaccine, would be infected for up to six months before the initiation of treatment. Treatment through direct-acting antivirals (DAAs) would be provided for free to all infected participants.

A very simplified diagram of how a vaccine efficacy CHIM (controlled human infection model) study, also known as a human challenge study, would work. DAA = direct-acting antiviral, a class of highly effective drugs used to treat hepatitis C.

With proper oversight and planning, risk to healthy volunteers would be low, because hepatitis C is reliably treatable with DAAs, and damage to the generally liver occurs over the course of decades. There is no evidence that infections for several months would cause lasting liver problems among otherwise healthy people (Hsu et al., 2023). Careful monitoring would also be employed to watch for a very rare complication, acute liver failure (also called fulminant hepatitis). Published case studies suggest that hepatitis C-induced acute liver failure can also be treated successfully with DAAs (Liang, Feld, Cox & Rice, 2021). A volunteer could withdraw from the study and request free treatment at any time.

Challenge studies would “down-select” vaccines in development, ensuring that only the most promising candidates are allocated resources for larger, more expensive, and time-consuming field studies. This would make development of a hepatitis C vaccine much less risky for researchers — failure would mean less wasted time and resources. It is possible that strong results in a challenge study could justify early deployment among at-risk populations like PWIDs, while field studies for global deployment among healthy individuals are conducted simultaneously.