Ebola and Marburg Virus Vaccines

Study Design:

This is an open label Phase I study to evaluate safety, tolerability, and immunogenicity of two recombinant DNA vaccines: one against Marburg virus infections and one against Ebola virus infections. The hypothesis is that each vaccine will be safe for human administration and elicit a humoral and T cell mediated immune response. The primary objectives are to evaluate the safety and tolerability of the investigational vaccines in healthy adults. Secondary and exploratory objectives are related to the immunogenicity of each study vaccine.

Product Description:

VRC-MARDNA025-00-VP (Marburg DNA) is composed of one closed-circular DNA plasmid encoding for the glycoprotein (GP) from the Angola strain of Marburg. VRC-EBODNA023-00-VP (Ebola DNA WT) is composed of two closed-circular DNA plasmids, one encodes for GP from the Zaire strain and one encodes for GP from the Sudan-Gulu strain of Ebola. DNA vaccine vials will be supplied at 4 mg/mL. Each DNA vaccination will be 1 mL of vaccine administered intramuscularly (IM) into the deltoid muscle using the Biojector\[R\] 2000 Needle-Free Injection Management System (Biojector).

Subjects:

A total of 20 healthy adults, ages 18-60 years, will be enrolled into two groups of 10 subjects each. No more than one subject per group may be in the age range of 51-60 years.

Study Plan:

Subjects will be sequentially enrolled into two groups. Group 1 subjects will receive the Marburg DNA vaccine and Group 2 subjects will receive the Ebola DNA WT vaccine. The first 3 enrollments in each group will occur no faster than one per day. Before completing enrollment into each group, there will be a study pause with review by the Protocol Safety Review Team (PSRT) when there is at least 2 weeks of safety follow-up on the third subject's first injection. Before the initiation of Group 2, the FDA must have assessed administration of the Ebola DNA WT vaccine as safe to proceed. In addition, there will be a study pause with review by the PSRT when there is at least two weeks of safety follow-up on the last subject enrolled into Group 1.

VRC 206 Group 1 will receive Marburg DNA, accrue 10 subjects and deliver injections on Day 0 with a dose 4 mg, Day 28 plus or minus 7 with a dose 4 mg and Day 56 plus or minus 7 with a dose 4 mg.

VRC 206 Group 2 will receive Ebola DNA WT, accrue 10 subjects and deliver injections on Day 0 with a dose of 4 mg, Day 28 plus or minus 7 with a dose 4 mg and Day 56 plus or minus 7 with a dose 4 mg.

The total accrual will be 20 subjects. The injections will be administered at least 21 days between DNA injections.

The original protocol design required 9 clinic visits and 3 telephone follow-up contacts for each subject.

The Version 4.0 protocol amendment allows a 4th injection for those who consent. Consent and administration of the 4th injection could occur anytime in the interval starting with Study Week 32 through Study Week 52. The 4th injection follow-up schedule includes 1 telephone contact and 4 follow-up visits after the injection.

Study Duration: The original study requires 32 weeks of clinical follow up for each participant. Subjects who consent to the amended schedule with a 4th injection will have an additional 12 weeks of follow up.