Clinical trial NCT02598388: Safety, Tolerability and Immunogenicity Study of 2-dose Heterologous Regimens for Ebola Vaccines Ad26.ZEBOV/MVA-BN-Filo
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemorrhagic Fever, Ebola
Keywords: 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
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2015-11-05
Enrollment: 578
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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 Ad26.ZEBOV 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.

Eligibility 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

Primary outcomes:
measure: Part 1, Part 2 (Group 2): Number of Participants With Unsolicited Adverse Events
timeFrame: Up to 28 days post each dose (up to Day 43)
measure: Part 2 (Group 1): Number of Participants With Unsolicited Adverse Events
timeFrame: Up to 28 days post dose 2 visit (up to Day 57)
measure: Part 1, Part 2 (Group 2): Number of Participants With Serious Adverse Events (SAEs)
timeFrame: Up to 1 year post dose 2 (up to Day 380)
measure: Part 2 (Group 1): Number of Participants With SAEs
timeFrame: Up to 1 year post dose 2 (up to Day 394)
measure: Part 1, Part 2 (Group 2): Number of Participants With Immediate Reportable Events (IREs)
timeFrame: Up to 1 year post dose 2 (up to Day 380)
measure: Part 2 (Group 1): Number of Participants With IREs
timeFrame: Up to 1 year post dose 2 (up to Day 394)
measure: Parts 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) 7 Days Post First Vaccination
timeFrame: 7 days post dose 1 (up to Day 8)
measure: Part 1, Part 2 (Group 2): Number of Participants With Solicited Local AEs 7 Days Post Second Vaccination
timeFrame: 7 days post dose 2 (up to Day 22)
measure: Part 2 (Group 1): Number of Participants With Solicited Local AEs 7 Days Post Second Vaccination
timeFrame: 7 days post dose 2 (up to Day 36)
measure: Parts 1 and 2: Number of Participants With Solicited Systemic Adverse Events 7 Days Post First Vaccination
timeFrame: 7 days post dose 1 (up to Day 8)
measure: Part 1, Part 2 (Group 2): Number of Participants With Solicited Systemic AEs 7 Days Post Second Vaccination
timeFrame: 7 days post dose 2 (up to Day 22)
measure: Part 2 (Group 1): Number of Participants With Solicited Systemic AEs 7 Days Post Second Vaccination
timeFrame: 7 days post dose 2 (up to Day 36)
measure: Part 1, Part 2 (Group 2): Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Filovirus Animal Non-Clinical Group (FANG) Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: 21-days post dose 2 (up to Day 36)
measure: Part 2 (Group 1): GMCs of Binding Antibody Levels Against EBOV GP Measured Using FANG ELISA
timeFrame: 21-days post dose 2 (Day 50)
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Solicited AEs: Up to 7 days post each vaccination (Up to Day 36); Unsolicited AEs: Up to 28 days post each vaccination (Up to Day 57)
Other outcomes:
Locations:
city: Silver Spring
country: United States
state: Maryland
city: Kericho
country: Kenya
city: Kisumu
country: Kenya
city: Maputo
country: Mozambique
city: Abuja
country: Nigeria
city: Mbeya
country: Tanzania
city: Kampala
country: Uganda
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References: