Safety, Tolerability and Immunogenicity Study of 2-dose Heterologous Regimens for Ebola Vaccines Ad26.ZEBOV/MVA-BN-Filo

• ClinicalTrials.gov Identifier: NCT02598388
• Recruitment Status: Completed
• First Posted: November 5, 2015
• Last Update Posted: October 25, 2019
• Sponsor: Janssen Vaccines & Prevention B.V.
• Collaborator: Walter Reed Army Institute of Research (WRAIR)
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Study Description

Brief Summary:

The purpose of this study is to assess the safety, tolerability and immunogenicity of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as 2-dose heterologous regimens in healthy and in HIV-infected adults.

Condition or disease	Intervention/treatment	Phase
Hemorrhagic Fever, Ebola	Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo	Phase 2

Detailed Description:

This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, 2-part, Phase 2 study of Ad26.ZEBOV and MVA-BN-Filo in healthy and HIV infected adults. In part 1, dose 1 vaccination with MVA-Bn-Filo will be followed by dose 2 vaccination with Ad26 14 days later in the US. In part 2, two regimens will be investigated. The first regimen will be Ad26 dose 1 vaccination followed by MVA-BN-Filo dose 2, 28 days later and the second regimen will be MVA-BN-Filo dose 1 vaccination followed by MVA-BN-Filo dose 2, 14 days later in Africa. The study consists of a Screening phase of up to 8 weeks (starting from the moment the participants signs the ICF), a Vaccination Phase, in which participants will be vaccinated at baseline (Day 1) followed by a dose 2 vaccination on Day 15 or 29, and a post-dose 2 follow-up phase of maximum 1 year post-dose 2 vaccination. Upon completion of 6-month post dose 2 visit those participants who received active vaccine will enter long-term follow-up until the 1 year post dose 2 vaccination visit to assess long-term safety and immunogenicity.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 578 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo
• Actual Study Start Date: December 10, 2015
• Actual Primary Completion Date: December 12, 2018
• Actual Study Completion Date: December 12, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 (US Participants); Participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15.	Biological: Ad26.ZEBOV; One 0.5 mL intramuscular (IM) injection of (5x10*10 viral particles).; Biological: MVA-BN-Filo; One 0.5 mL IM injection of (1x10*8 infectious units).; Biological: Placebo; One 0.5 mL IM injection of 0.9 percent (%) saline.
Experimental: Part 2 Group 1 (African Participants); Participants will receive Ad26.ZEBOV or placebo on Day 1 followed by MVA-BN-Filo or placebo on Day 29.	Biological: Ad26.ZEBOV; One 0.5 mL intramuscular (IM) injection of (5x10*10 viral particles).; Biological: MVA-BN-Filo; One 0.5 mL IM injection of (1x10*8 infectious units).; Biological: Placebo; One 0.5 mL IM injection of 0.9 percent (%) saline.
Experimental: Part 2 Group 2 (African Participants); Participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15.	Biological: Ad26.ZEBOV; One 0.5 mL intramuscular (IM) injection of (5x10*10 viral particles).; Biological: MVA-BN-Filo; One 0.5 mL IM injection of (1x10*8 infectious units).; Biological: Placebo; One 0.5 mL IM injection of 0.9 percent (%) saline.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Adverse Events [ Time Frame: Up to Day 42 post-dose 2 visit ]
2. Number of Participants With Serious Adverse Events [ Time Frame: Continuous throughout the duration of the study (up to 1 year post dose 2 visit +/- 1 month) ]
3. Number of Participants with Solicited Local and Systemic Adverse Events [ Time Frame: Up to 7 days after each study vaccination ]
4. Ebola Virus Glycoprotein (EBOV GP)-specific Antibody Concentrations Measured by an Ezyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Up to day 21 after dose 2 vaccination ]

Secondary Outcome Measures :

1. Comparison of Safety and Tolerability of Ad26.ZEBOV/MVA-BN-Filo and MVA-BN- Filo/Ad26.ZEBOV Regimens Between Healthy and HIV-Infected Adults [ Time Frame: Up to 1 year post dose 2 ]
   The comparison will be made on the basis of treatment emergent adverse events as well as comparison of the solicited local and systemic adverse events for tolerability.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Participant must be healthy in the Investigator's clinical judgment on the basis of medical history, physical examination and vital signs performed at Screening
• Participant must be healthy on the basis of clinical laboratory tests and electrocardiogram (ECG) (only in participants >50 years) performed at Screening. If the results of the laboratory screening tests and ECG are outside the institutional normal reference ranges, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study
• A woman of childbearing potential must have a negative urine β-human chorionic gonadotropin [beta-hCG] pregnancy test at Screening and a negative urine [beta-hCG] pregnancy test immediately prior to each study vaccine administration
• A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to dose 1 vaccination until at least 3 months after the dose 2 vaccination, unless a vasectomy was performed more than 1 year prior to Screening
• Participant must pass the test of understanding (TOU)
• Additional Inclusion Criteria for HIV-infected participants a) participants must have a positive HIV-1 and/or -2 serology test within 6 months of screening, including the day of screening; b) participants must have a Screening CD4+ cell count >200 cells/microliter (mcL); c) in part 1, all participants must be on a stable highly active antiretroviral therapy (HAART) regimen for 4 weeks prior to Screening, in part 2 participants with screening CD4+ cell count <350 cells/mcL must also be on a stable HAART regimen for 4 weeks prior to Screening

Exclusion Criteria:

• Has received any candidate Ebola vaccine
• Diagnosed with Ebola virus disease, or prior exposure to EBOV, including travel to epidemic Ebola areas less than 1 month prior to Screening
• Has received any experimental candidate Ad26- or MVA-based vaccine in the past or received any other investigational drug or investigational vaccine or used an invasive investigational medical device within 3 months prior to Screening
• Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products
• Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, other systemic infections) or clinically significant findings during screening of medical history, ECG (only in participants >50 years), physical examination, vital signs or laboratory testing for which, in the opinion of the investigator, participation would not be in the best interest of the participants (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments

Contacts and Locations

Locations

United States, Maryland

Silver Spring, Maryland, United States

Kenya

Kericho, Kenya

Kisumu, Kenya

Mozambique

Maputo, Mozambique

Nigeria

Abuja, Nigeria

Tanzania

Mbeya, Tanzania

Uganda

Kampala, Uganda

Sponsors and Collaborators

Janssen Vaccines & Prevention B.V.

Walter Reed Army Institute of Research (WRAIR)

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial; Janssen Vaccines & Prevention B.V.

More Information

• Responsible Party: Janssen Vaccines & Prevention B.V.
• ClinicalTrials.gov Identifier: NCT02598388 History of Changes
• Other Study ID Numbers: CR108062; VAC52150EBL2003 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
• First Posted: November 5, 2015
• Last Update Posted: October 25, 2019
• Last Verified: October 2019

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Vaccines & Prevention B.V.:

Healthy; Vaccine; Ebola viruses; Ebola virus disease (EVD); Filoviruses; Hemorrhagic fever; Monovalent vaccine; Human adenovirus serotype 26 (Ad26) encoding the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV); Modified Vaccinia Virus Ankara - Bavarian Nordic (MVA-BN) Filo-vector; Safety; Immunogenicity

Additional relevant MeSH terms:

Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Filoviridae Infections; Mononegavirales Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs