Multiple Treatments for Ebola Virus Disease (EVD)

An Adaptive Randomized Trial Comparing Multiple Treatments for Ebola Virus (EBOV) Infected Children and Adults

Bill and Melinda Gates Foundation, Duke University, University of Sierra Leone, Syneos Health, University of North Carolina

The purpose of this study is to determine whether multiple therapeutic regimens are effective in the treatment of Ebola Virus Disease (EVD)

The ongoing epidemic of EVD has ravaged parts of West Africa, with initial cases reported in December 2013. There is no licensed specific therapy for the disease, which has a case-fatality rate of approximately 50-70%. Although anecdotal clinical data, recent studies in animal models, and in vitro screening suggest that treatment of EVD patients with anti-viral agents, immune modifying agents, and/or convalescent blood products may be effective, they have not been evaluated in clinical trials. This multi-arm clinical trial will evaluate the efficacy and safety of multiple regimens, both as mono-therapy and combination therapy. Provision of these regimens, if found effective and safe, would have a major impact on the current and future epidemics by providing effective treatment options. As described for previous adaptive trials, a randomization probability for each of the treatment regimens is created based on 14-day mortality, and is used for weighting randomization of subsequently enrolled participants. Participants will continually be preferentially assigned to regimens with better initial performance. New agents can be added or existing agents removed as the trial evolves.

Adults (>18 yrs): 3 x 500mg tablets daily for 5 days; Children (6 months to <18 yrs): 30mg/kg (oral suspension) daily for 5 days

Sunitinib - Adults (>18 yrs): 1 x 50mg tablet daily for 7 days; Children (6 months to <18 yrs): 0.83 mg/kg (oral suspension) daily for 7 days. Erlotinib - Adults (>18 yrs): 1 x 150mg tablet daily for 7 days; Children (8kg to <20kg): 3.5 mg/kg daily for 7 days; Children (>20kg to <30kg): 3.0 mg/kg daily for 7 days; Children (>30kg to < 18 yrs): 25 mg/kg daily for 7 days

Atorvastatin - Adults (>18 yrs): 1 x 40mg tablet daily until discharge; Children (6 years to <18 yrs): 1 x 40mg tablet daily until discharge; Irbesartan - Adults (>18 yrs): 1 x 150mg tablets daily until discharge; Children (6 years to <18 yrs): 1 x 75mg tablet daily until discharge.

All arms will receive aggressive IV fluid rehydration and frequent laboratory tests to assist with medical management as indicated.

Severe adverse events that are inconsistent with EVD and are assessed as related to study agent(s) by the site principal investigator

Inclusion Criteria: Males and females aged 6 months and >8kg in weight Confirmed case of EVD Admission to the hospital < 48 hours prior to enrollment Participant or family member/guardian able and willing to provide signed informed consent Exclusion Criteria: Prior treatment with any other specific experimental anti-EVD product, or expectation to receive another experimental anti-EVD product during the course of the study (this does not include general supportive care or nutritional supplements routinely administered to all hospitalized patients with EVD) Unresponsive In the treating physicians opinion, an inability to comply with the study treatment regimen

Berry SM, Petzold EA, Dull P, Thielman NM, Cunningham CK, Corey GR, McClain MT, Hoover DL, Russell J, Griffiss JM, Woods CW. A response adaptive randomization platform trial for efficient evaluation of Ebola virus treatments: A model for pandemic response. Clin Trials. 2016 Feb;13(1):22-30. doi: 10.1177/1740774515621721. Epub 2016 Jan 14.