Protocol No: ECCT/23/07/05 Date of Protocol: 06-12-2022

Study Title:
A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral-Vectored Marburg Virus Vaccine in Healthy Adults 
Study Objectives:
Primary Objective 
To evaluate the safety and tolerability of cAd3-Marburg vaccine
Secondary objective
To evaluate the antibody response (IgG) to cAd3-Marburg vaccine at Day 29 post-vaccination.
Other secondary objective
To determine the antibody (IgG) response  to cAd3-Marburg vaccine across additional timepoints post-vaccination. 
Exploratory Objective
To describe the antibody response (IgM) to cAd3-Marburg vaccine.
To describe the neutralizing antibody response to cAd3-Marburg vaccine. 


Laymans Summary:
This is a multi-center, double-blinded, placebo-controlled, Phase II study to evaluate safety, tolerability, and immunogenicity of a single dose of cAd3-Marburg vaccine in healthy adults up to 70 years of age, in Uganda and Kenya. The study will enroll 125 eligible participants randomized 4:1 to receive the cAd3-Marburg vaccine at 1.0 × 10^11 PU dose or placebo (0.9% sodium chloride (NaCl) solution) at Day 1, intramuscularly in deltoid muscle. Participants will be screened for eligibility up to 28 days before enrollment. Enrollment will be staggered, starting with healthy adults 18 to 50 years of age (inclusive). Upon enrollment of minimum 25 younger adult participants (sentinel), the safety data up to 7 days post vaccination of these 25 sentinel participants will be reviewed by the independent DSMB. Progression to enrollment of the older adults (>50 to 70 years of age) will be dependent on the unblinded review of the Data Safety Monitoring Board (DSMB). Safety and immunogenicity will be assessed at Days 1, 8, 15, 29, 85, 169, and will conclude at the end of study visit on Day 366.


Abstract of Study:
Background Information: 
Marburg virus (MARV) is one of the 6 genera in the family Filoviridae, which, along with Ebolavirus and Cuevavirus, are known to induce viral hemorrhagic fever. MARV is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single GP. In humans, MARV is responsible for causing MVD, formerly known as Marburg hemorrhagic fever. It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people and indirect contact with contaminated environments. MVD has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of non-specific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias,
and/or arthralgias, and diarrhea can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes (WHO 2021). In the last decades, MARV has been associated with large outbreaks of MVD in Africa; the average case fatality rate is around 50%, varying from 23% to 90% depending
on virus strain and case management (CDC 2021).  The MARV is the etiologic agent of MVD and has been associated with 12 major outbreaks; the 2 largest occurring in Africa (Democratic Republic of Congo from 1998 to 2000 and Angola in 2005) that resulted in case fatality rates over 80%. The first recorded case of MVD in Guinea and West Africa occurred in August 2021 and resulted in 1 fatality. Recently 2 fatal cases of MVD were reported from Ashanti region, Ghana in June 2022 (WHO 2022). There is a continued potential threat of spread to other countries given the frequency of international travel (IB 2022). Sabin cAd3-Marburg vaccine is supplied as a single-dose vial that contains a recombinantcAd3 vector that expresses WT GP from the Angola strain of the MARV. The primary goal of
the cAd3-Marburg vaccine is to induce rapid immunity followed by durable protection against MVD.