Clinical Trial Update - A5360: MINMON Study

A5360: A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study

The discovery of the hepatitis C virus (HCV) in 1989 and the development of medicines used to treat it is a truly remarkable story which encapsulates the goals of translational medicine from the bench to the bedside and beyond. In the late 1990s, a breakthrough was the development of a laboratory model of HCV infection, which allowed for scientific discovery, including the identification of antiviral drugs known as direct acting antivirals (DAAs). Taken as combinations of antivirals, these DAAs can cure all strains of HCV (known as genotypes) with 8 to 12 weeks of therapy. Global elimination of HCV infection is feasible but there are numerous, daunting challenges, including cost of therapy, which has been declining with the help of generic manufacturing. The simplification of the HCV treatment pathway is essential for improving access to curative therapies by expanding access to treatment into communities, as well as reducing the requirement for laboratory testing.  With that in mind, Protocol A5360: A Single-arm Study to Evaluate the Feasibility and Efficacy of a Minimal Monitoring Strategy to Deliver Pan-genotypic Ribavirin-free HCV Therapy to HCV Infected Populations who are HCV Treatment Naïve with Evidence of Active HCV Infection: The MINMON Study, was created. A5360 is being led by Mark Sulkowski, MD, Investigator at our Johns Hopkins University Clinical Research Site in Baltimore, MD and is expected to begin enrolling study participants in early 2018.

The A5360 study is a single arm cohort of 400 participants, all of whom will receive the drug sofosbuvir/velpatasvir (Epclusa) and will take one tablet daily for 12 weeks. Enrolling sites will be based in Africa, Brazil, India, Thailand and the United States with two-thirds of participants being enrolled at international sites. Following HCV treatment, participants will be followed for an additional 72 weeks to assess the long-term outcomes related to HCV and liver disease, including the incidence of HCV reinfection.

“One of the main issues that some countries face is a limited number of clinicians trained to treat HCV infection. HCV treatment has traditionally been delivered by liver or infectious diseases specialists,” said Dr. Sulkowski. “In both international and domestic settings, these experts are relatively few and are often not within reach of persons with HCV infection. If a more cost-effective and efficient treatment delivery plan can be established, it has the potential to greatly expand the number of people that can achieve HCV cure.”

In some parts of the United States, the health care system itself creates major barriers to an HCV cure by requiring individuals to present on specific dates and times for visits, to fill prescriptions at specific pharmacies in 28 day intervals, and to complete a long list of requirements to access therapy, including being treated by specialists trained in gastroenterology/hepatology or infectious diseases. A5360 will deliver HCV treatment without traditional laboratory and clinical monitoring.  While the treatment of HCV with sofosbuvir/velpatasvir (Epclusa) has been shown to be safe and effective in clinical practice, the A5360 study represents a novel approach of minimal monitoring. It is critical to demonstrate that this strategy is effective in all settings, regardless of access to resources.

“We know that HCV treatment for 84 days is safe and effective; I think in some situations – it might be best if clinicians just stay out of the way. We plan to utilize communication via phone or other electronic means such as text messaging during the 84-day period,” said Dr. Sulkowski. “The key is to empower study participants by having them select the communication method they prefer and we will accommodate. Of course, if participants have problems or other issues that require a visit, they will be seen quickly, but these will be on an as-needed basis and not planned visits.”

There is no doubt that the tools to cure hepatitis C in most persons who can access therapy are available. To that end, the World Health Organization (WHO) has announced a global strategy to eliminate HCV by 2030 by increasing the rate of HCV diagnosis, and improving linkage to care, treatment and cure dramatically. The minimal monitoring approach that is being tested in A5360 is essential to meeting these goals.

“The A5360 study is a great example of the capacity of the ACTG as a clinical trials network funded by NIAID to conduct high-impact implementation research,” said Daniel Kuritzkes, MD, ACTG Network Principal Investigator and Chair. “If successful, the strategy of minimal monitoring patients receiving treatment for HCV infection could play a critical role in reaching the WHO goal of eliminating HVC infection by 2030.”

The A5360 team is truly global with crucial contributions from Sunil Solomon, MD, Investigator at our Chennai, India Clinical Research Site, as well as Johns Hopkins University; Sandra Wagner Cardoso, MD, Investigator at our Rio de Janeiro, Brazil Clinical Research Site; and Anchalee Avihingsanon, MD, Investigator at our Bangkok, Thailand Clinical Research Site.

Globally, nearly 71 million people are chronically infected with HCV; of whom, an estimated 4 to 5 million are coinfected with HIV. In this context, advances in treatment delivery are urgently needed and A5360 will guide novel strategies that have the potential to significantly reduce the need for laboratory testing and skilled health care workers which will allow for more patients to be treated.