Ebola CVD-Mali #2000 (Bivalent) VRC-EBOAdc069-00-vp (cAd3-EBO)

Ebola Virus Disease Clinical Trial

Official title: A PHASE IB, DOUBLE-BLIND, CLINICAL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF TWO DIFFERENT DOSAGE LEVELS OF EBOLA CHIMPANZEE ADENOVIRUS VECTOR VACCINE "VRC-EBOADC069-00-VP (cAd3-EBO)" AND THE HETEROLOGOUS PRIME-BOOST CANDIDATE VACCINE REGIMEN OF cAD3-EBO FOLLOWED BY MVA-VECTORED VACCINE IN HEALTHY ADULTS, 18-65 YEARS OF AGE, IN BAMAKO, MALI

Status Completed

Clinical Trial Summary

Ebola virus causes an infection known as Ebola virus disease (EVD). This it is generally a severe disease which can also lead to death. The 2014 outbreak of EVD in West Africa is the largest ever. Researchers want to develop a vaccine to prevent Ebola infection.

This study will assess the safety of a single dose of the bivalent Ebola Zaire candidate vaccine VRC-EBOADC069-00-VP (cAD3-EBO) when administered to healthy Malian adult volunteers, age 18-65 years (mostly health care workers and other front line workers [e.g., individuals who incinerate contaminated materials]), at one of 2 dosage levels, 2.0 x 10(10) vp or 2 x 10(11) vp. It is impossible for someone to get an Ebola infection from this vaccine.

Heterologous booster dose allocation - Each participant will be offered the opportunity to be included in the booster step of this study. After obtaining consent and the additional review of pertinent medical history, participants in each group will be randomized to receive the candidate booster vaccine, MVA-EbolaZ or placebo.

This will be the first clinical trial in Mali with bivalent cAd3-based Ebola vaccine and the first where the dosage level contains > 10(11) vp. It follows completion of a Phase Ib trial in Malian health care workers that tested three dosage levels of monovalent cAd3-EBO Z vaccine. The data generated in West Africans (Mali) on the tolerability and immunogenicity of the bivalent vaccine will be compared to clinical and immunologic responses documented in in parallel studies in East African subjects (Uganda) and North American subjects (NIH, Bethesda, MD, USA).

Objectives:

• To see if an Ebola vaccine is safe and to study immune responses to it.

• To study the effect of the MVA-EbolaZ booster on the immune response

Eligibility:

• Healthy adults ages 18-65.

Clinical Trial Description

This is a phase 1B, double-blind, randomized study to examine the safety, tolerability and immunogenicity of two different dosage levels of investigational Ebola vaccine.

The vaccine is a recombinant chimpanzee adenovirus Type 3-vectored Ebolavirus vaccine (cAd3-EBO), VRC-EBOADC069-00-VP. The vaccine encodes wild type (WT) glycoproteins (GP) from Zaire and Sudan species of Ebola virus. The primary objective is to assess the safety of a single dose intramuscular injection of the bivalent vaccine at one of 2 dosage levels, 2.0 X 10(10) vp or 2 x 10(11) vp and to assess the safety of the heterologous prime boost regimen of cAd3-EBO followed by MVA-EbolaZ or Phosphate Buffered Saline (PBS) placebo. A secondary objective is to assess the immunogenicity generated by 2 different dosage levels of the bivalent Ebola candidate vaccine.

Enrolment of Group 1 participants:

The first 20 Malian volunteers will be vaccinated in a staggered fashion. For safety reasons, the first 10 Malian subjects to receive a vaccine dose in Group 1 will be vaccinated on day 1 and we will wait 24 hours before vaccinating 10 subsequent volunteers. After these 20 volunteers in Group 1 have been vaccinated and followed up for 7 days, an interim safety review (ISR1) will be performed by the DSMB. Enrolment of subjects into Group 2 will commence only after the DSMB has assessed the data and indicated that it is safe to do so.

Half of Group 1 participants will be randomly assigned to receive the low dose and the remaining 10 will be randomized to receive the high dose.

Enrolment of Group 2 participants:

The 40 subjects in Group 2 will be accrued as rapidly as possible. The 40 Malian volunteers in Group 2 will be vaccinated over several days to limit wastage of the available doses of cAd3 EBO. As a result, a proposed scheme would be 10 per vaccination day. This could be adjusted as needed to limit wastage but no more than 20 participants would be vaccinated in 1 day. After the total of 40 volunteers in Group 2 have been vaccinated and followed up for 7 days, an interim safety review (ISR2) will be performed by the DSMB.

Prime Boost Vaccine Randomization 4-16 weeks after priming dose: Each participant will be offered the opportunity to be included in the booster step of this study. After obtaining consent and the additional review of pertinent medical history, participants in each group will be randomized to receive the candidate booster vaccine, MVA-EbolaZ or PBS placebo ;

Related Conditions & MeSH terms

• Ebola Virus Disease
• Hemorrhagic Fever
• Hemorrhagic Fever, Ebola
• Virus Diseases

• NCT number: NCT02368119
• Study type: Interventional
• Source: University of Maryland, Baltimore
• Status: Completed
• Phase: Phase 1
• Start date: March 2015
• Completion date: September 27, 2016