A Study to Assess Safety, Tolerability, and Immunogenicity of Three Heterologus 2-dose Regimens of the Candidate Prophylactic Vaccines for Ebola in Healthy Adults

NCT ID: NCT02416453

Last Updated: 2021-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 423 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-15
• Study Completion Date: 2018-01-19

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.

Conditions

Ebola Viral Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Group 1

Participants will receive intramuscular (IM) injection of Ad26.ZEBOV/Placebo on Day 1 followed by IM injection of MVA-BN-Filo/Placebo on Day 29.

Group Type: EXPERIMENTAL

MVA-BN-Filo

Intervention Type: BIOLOGICAL

One 0.5 mL intramuscular (IM) injection of 1E8 Infectious Unit \[Inf. U.\] on Day 29, 57, or 85.

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1.

Placebo

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 0.9% saline on Day 1 and Day 29, 57, or 85.

Group 2

Participants will receive IM injection of Ad26.ZEBOV/Placebo on Day 1 followed by IM injection of MVA-BN-Filo/Placebo on Day 57.

Group Type: EXPERIMENTAL

MVA-BN-Filo

Intervention Type: BIOLOGICAL

One 0.5 mL intramuscular (IM) injection of 1E8 Infectious Unit \[Inf. U.\] on Day 29, 57, or 85.

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1.

Placebo

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 0.9% saline on Day 1 and Day 29, 57, or 85.

Group 3

Participants will receive IM injection of Ad26.ZEBOV/Placebo on Day 1 followed by IM injection of MVA-BN-Filo/Placebo on Day 85.

Group Type: EXPERIMENTAL

MVA-BN-Filo

Intervention Type: BIOLOGICAL

One 0.5 mL intramuscular (IM) injection of 1E8 Infectious Unit \[Inf. U.\] on Day 29, 57, or 85.

Ad26.ZEBOV

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1.

Placebo

Intervention Type: BIOLOGICAL

One 0.5 mL IM injection of 0.9% saline on Day 1 and Day 29, 57, or 85.

Interventions

MVA-BN-Filo

One 0.5 mL intramuscular (IM) injection of 1E8 Infectious Unit \[Inf. U.\] on Day 29, 57, or 85.

Intervention Type: BIOLOGICAL

Ad26.ZEBOV

One 0.5 mL IM injection of 5E10 viral particles (vp) on Day 1.

Intervention Type: BIOLOGICAL

Placebo

One 0.5 mL IM injection of 0.9% saline on Day 1 and Day 29, 57, or 85.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

Janssen Vaccines & Prevention B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Vaccines & Prevention B.V. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Vaccines & Prevention B.V.

Inserm Clinical Trials

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Créteil, , France

Marseille, , France

Paris, , France

Pierre-Bénite, , France

Rennes, , France

Saint-Etienne, , France

Strasbourg, , France

Tours, , France

London, , United Kingdom

Oxford, , United Kingdom

Southampton, , United Kingdom

Countries

France; United Kingdom

References

Lacabaratz C, Durand M, Wiedemann A, Foucat E, Surenaud M, Krief C, Guillaumat L, Robinson C, Luhn K, Bockstal V, Thiebaut R, Richert L, Levy Y. Innate and Cellular Immune Response to the Ebola Vaccine Ad26.ZEBOV, MVA-BN-Filo: An Ancillary Study of the EBL2001 Phase 2 Trial. J Infect Dis. 2025 Feb 4;231(1):230-240. doi: 10.1093/infdis/jiae360.

Reference Type: DERIVED

PMID: 39012798 (View on PubMed)

Barry H, Lhomme E, Surenaud M, Nouctara M, Robinson C, Bockstal V, Valea I, Somda S, Tinto H, Meda N, Greenwood B, Thiebaut R, Lacabaratz C. Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. PLoS Negl Trop Dis. 2024 Apr 11;18(4):e0011500. doi: 10.1371/journal.pntd.0011500. eCollection 2024 Apr.

Reference Type: DERIVED

PMID: 38603720 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33217361 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

VAC52150EBL2001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000596-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107227

Identifier Type: -

Identifier Source: org_study_id