Clinical trial NCT02416453: A Study to Assess Safety, Tolerability, and Immunogenicity of Three Heterologus 2-dose Regimens of the Candidate Prophylactic Vaccines for Ebola in Healthy Adults
Official title: A Randomized, Observer-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Three Prime-Boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo in Healthy Adults in Europe
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ebola Viral Disease
Keywords: Healthy
Ebola viruses
Ebola Viral Disease (EVD)
Filoviruses
Monovalent vaccine
Human adenovirus serotype 26 (Ad26) encoding the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV)
Modified Vaccinia Virus Ankara - Bavarian Nordic Filo-vector (MVA-BN Filo)
Safety
Immunogenicity
Inserm and University of Oxford
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: University of Oxford
First posted: 2015-04-15
Enrollment: 423
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of 3 vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as 2-dose heterologous regimens.

Detailed description: This is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, Phase 2 study evaluating the safety, tolerability and immunogenicity of 2-dose heterologous regimens using Ad26.ZEBOV and MVA-BN-Filo administered to healthy adults participants in Europe. The study involves a screening period of up to 12 weeks, a vaccination period in which participants will be vaccinated with Ad26.ZEBOV (dose 1) followed by vaccination with MVA-BN-Filo (dose 2) 28, 56 or 84 days later, and a post-vaccination phase until 6 months post dose 2 visit (Days 209, 237 or 265). After unblinding, only participants who received Ad26.ZEBOV and/or MVA-BN-Filo will continue the study until the Day 365 visit (or until the start of the roll-over study or for an additional 12 months \[whichever comes first\] for participants in France who agree to continue the long-term follow-up after Day 365) to assess long-term safety and immunogenicity. Participants will enroll into 3 cohorts: that is, Cohort 1 (Participants will receive Ad26.ZEBOV and MVA-BN-Filo in an open-label fashion), Cohort 2 (Participants will be randomized to receive the 2-dose heterologous vaccine regimen with either Ad26.ZEBOV followed by MVA-BN-Filo, or placebo in a 14:1 ratio) and Cohort 3 (Participants will be randomized to receive the 2-dose heterologous vaccine regimen with either Ad26.ZEBOV followed by MVA-BN-Filo, or placebo in a 10:3 ratio). In Cohorts 2 and 3, core immunogenicity assessments (humoral and cellular assays) will be performed. In Cohort 2, additional immunogenicity assessments will be done. In Cohort 1, plasma blast response kinetics will be evaluated. Safety will be monitored during the study.

Eligibility criteria: Inclusion Criteria:

* Must be healthy in the Investigator's clinical judgment on the basis of medical history, physical examination, electrocardiogram (ECG) and vital signs performed at Screening
* Must be healthy on the basis of clinical laboratory tests performed at Screening. If the results of the laboratory screening tests are outside the 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
* Before randomization, a woman must be either of childbearing potential and practicing (or intending to practice) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies, beginning at least 28 days prior to vaccination OR not of childbearing potential: postmenopausal (greater than \[\>\] 45 years of age with amenorrhea for at least 2 years or lesser than or equal to \[\<=\] 45 years of age with amenorrhea for at least 6 months, and a serum follicle stimulating hormone (FSH) level \>40 international unit per milliliter \[IU/L\]); permanently sterilized (for example, bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy
* Woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at Screening and a negative urine beta-hCG pregnancy test immediately prior to each study vaccine administration
* Man who is sexually active with a woman of childbearing potential and has not had a vasectomy performed more than 1 year prior to screening must be willing to use condoms for sexual intercourse beginning prior to enrollment

Exclusion Criteria:

* Having received any candidate Ebola vaccine
* Diagnosed with Ebola virus disease, or prior exposure to Ebola virus, including travel to West Africa less than 1 month prior to screening. West Africa includes but is not limited to the countries of Guinea, Liberia, Mali, and Sierra Leone
* Having received any experimental candidate adenovirus serotype 26 (vector: Ad26) or Modified Vaccinia Ankara (MVA-) based vaccine in the past
* Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines including known allergy to egg, egg products and aminoglycosides
* Presence of acute illness or temperature greater than or equal to 38.0 C on Day 1

Primary outcomes:
measure: Number of Participants With Unsolicited Adverse Events (Groups 1, 2 and 3)
timeFrame: Up to 42-day post dose 2 visit (Day 1 to Day 127)
measure: Number of Participants With Serious Adverse Events (Groups 1, 2 and 3)
timeFrame: Up to Day 365
measure: Number of Participants With Immediate Reportable Events (Groups 1, 2 and 3)
timeFrame: Up to Day 365
measure: Number of Participants With Solicited Local Adverse Events (Groups 1, 2 and 3)
timeFrame: 7 days post-dose 1 (Day 8)
measure: Number of Participants With Solicited Local Adverse Events (Groups 1, 2 and 3)
timeFrame: 7 days post-dose 2 (Up to Day 92)
measure: Number of Participants With Solicited Systemic Adverse Events (Groups 1, 2 and 3)
timeFrame: 7 days post-dose 1 (Day 8)
measure: Number of Participants With Solicited Systemic Adverse Events (Groups 1, 2 and 3)
timeFrame: 7 days post-dose 2 (Up to Day 92)
Secondary outcomes:
measure: Number of Participants With Unsolicited Adverse Events (Group 4)
timeFrame: Up to 28-day post dose 1 (Day 29)
measure: Number of Participants With Serious Adverse Events (Group 4)
timeFrame: Up to Day 180
measure: Number of Participants With Immediate Reportable Events (Group 4)
timeFrame: Up to Day 180
measure: Number of Participants With Solicited Local Adverse Events (Group 4)
timeFrame: 7 days after each vaccination (Up to Day 8)
measure: Number of Participants With Solicited Systemic Adverse Events (Group 4)
timeFrame: 7 days after each vaccination (Up to Day 8)
measure: 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) (Groups 1, 2 and 3)
timeFrame: At 21-days post dose 2 (Day 50 for Group 1; Day 78 for Group 2; and Day 106 for Group 3)
Other outcomes:
Locations:
city: Creteil
country: France
city: Marseille
country: France
city: Paris
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Saint Etienne
country: France
city: Strasbourg
country: France
city: Tours
country: France
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Inserm Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Pollard AJ, Launay O, Lelievre JD, Lacabaratz C, Grande S, Goldstein N, Robinson C, Gaddah A, Bockstal V, Wiedemann A, Leyssen M, Luhn K, Richert L, Betard C, Gibani MM, Clutterbuck EA, Snape MD, Levy Y, Douoguih M, Thiebaut R; EBOVAC2 EBL2001 study group. Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2021 Apr;21(4):493-506. doi: 10.1016/S1473-3099(20)30476-X. Epub 2020 Nov 17.