INTEGRATE

The challenge

Lassa fever, a viral haemorrhagic fever spread by contact with rodents carrying the virus or with infected patients, affects large parts of West Africa, particularly Nigeria. An infection with epidemic potential, it kills around 12% of hospitalised patients. Overall, it is responsible for an estimated 5,000 to 10,000 deaths every year. An increasing number of outbreaks have occurred in recent years.

Only one specific treatment exists, ribavirin, but there are significant doubts about its efficacy, and it can have significant side effects. Four drugs are under development. The most advanced, favipiravir, a licensed drug developed to treat influenza, has shown significant promise in preclinical and early clinical studies.

With no vaccine yet available for Lassa fever, cases apparently on the increase, and doubts about the efficacy of existing treatment, more therapeutics are urgently needed.

The project

Several European and African institutions have worked together for more than 15 years to better understand Lassa fever infections and improve detection. One objective has been to build the capacity of clinical sites in Nigeria, enabling them to conduct pharmacokinetic studies and undertake the phase IIa SAFARI clinical study, which is evaluating the efficacy and safety of different doses of favipiravir compared to ribavirin. 

Building on these efforts, the INTEGRATE project is further strengthening trial capacity so that additional clinical studies can be performed. In particular, it is establishing a multisite clinical trial platform able to conduct an adaptive trial of candidate Lassa fever therapeutics. The project is beginning with a head-to-head comparison of favipiravir versus ribavirin, informed by the results from the SAFARI trial, but will be able to introduce new drugs into the trial should they become available.

The project will also undertake an extensive programme of community engagement to ensure community support for the trial. Factors such as the stigma associated with Lassa fever infections could affect people’s willingness to take part in trials, and there is a need to understand the full range of factors that could potentially affect participation.

Preparatory work has been carried out at additional sites in Benin, Guinea, Liberia and Nigeria so that they can contribute to the trial. Clinical trials capacity is being developed not just by links to European institutions but also by drawing on the expertise of a regional centre of research excellence, CERMEL in Gabon, providing an example of South–South capacity-building. 

Impact

The INTEGRATE project will have a major impact on drug development for Lassa fever. It will:

• Provide key evidence on the efficacy and safety of favipiravir as a possible alternative to ribavirin.
• Drive improvements in care of Lassa fever patients at clinical sites.
• Accelerate the evaluation of additional drugs showing promise against Lassa fever.
• Reduce the costs and timescales of subsequent drug trials by providing an established platform and protocol.
• Build clinical trial capacity and expertise in Nigeria and other parts of West Africa. 

As favipiravir has already been licensed in some countries, it could potentially be introduced relatively quickly if shown to be safe and efficacious against Lassa fever, ensuring that populations in West Africa rapidly benefit from a new treatment for a major threat to health in the region.