A Study to Evaluate the Immunogenicity, Safety and Tolerability of Ad26.ZEBOV and MVA-BN-Filo in Healthy Adult Participants

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of a Heterologous Prime-Boost Regimen Using Three Different Batches of Ad26.ZEBOV and a Single Batch of MVA-BN®-Filo in Healthy Adult Subjects

The purpose of this study is to compare the humoral immune response induced by 3 different batches of Ad26.ZEBOV as measured by enzyme - linked immunosorbent assay (ELISA) against the Ebola virus (EBOV) GP (Glycoprotein) at 56 days post prime.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: Ad26.ZEBOV-Batch #1; Biological: MVA-BN-Filo; Biological: Ad26.ZEBOV-Batch #2; Biological: Ad26.ZEBOV-Batch #3; Biological: Placebo

Detailed Description

This is a randomized, double - blind, placebo - controlled, parallel - group, multicenter, Phase 3 study to evaluate the immunogenic equivalence of a heterologous prime - boost regimen using 3 different batches of Ad26.ZEBOV in healthy adult participants. The study consists of a screening period of up to 6 weeks, a vaccination period in which participants will be vaccinated at baseline (Day 1), followed by a boost vaccination on Day 57, and a post-vaccination phase until 6 months post-boost visit (Day 237). The participants will be randomized at baseline (on Day 1) in a 2:2:2:1 ratio to Groups 1, 2, 3 and 4. Safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 329
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States
  • California
    • San Diego, California, United States
  • Florida
    • Melbourne, Florida, United States
  • Illinois
    • Peoria, Illinois, United States
  • Indiana
    • Mishawaka, Indiana, United States
  • Maryland
    • Rockville, Maryland, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy in the Investigator's clinical judgment on the basis of medical history, physical examination, electrocardiogram (ECG) and vital signs performed at Screening
• Healthy on the basis of clinical laboratory tests performed at Screening
• 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 any 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, in addition to the documented birth control method used by the female partner

Exclusion Criteria:

• Having received a 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 centigrade (°C) on Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Ad26.ZEBOV -Batch #1, single dose intramuscular (IM) injection on Day 1; MVA-BN-Filo, single dose IM injection on Day 57	Biological: Ad26.ZEBOV-Batch #1; Ad26.ZEBOV - Batch #1, live, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles on Day 1; Biological: MVA-BN-Filo; MVA-BN-Filo- live replication incompetent vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit [Inf. U.] once on Day 57.
Experimental: Group 2; Ad26.ZEBOV -Batch #2, single dose intramuscular (IM) injection on Day 1; MVA-BN-Filo, single dose IM injection on Day 57	Biological: MVA-BN-Filo; MVA-BN-Filo- live replication incompetent vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit [Inf. U.] once on Day 57.; Biological: Ad26.ZEBOV-Batch #2; Ad26.ZEBOV - Batch #2, live, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles on Day 1
Experimental: Group 3; Ad26.ZEBOV -Batch #3, single dose intramuscular (IM) injection on Day 1; MVA-BN-Filo, single dose IM injection on Day 57	Biological: MVA-BN-Filo; MVA-BN-Filo- live replication incompetent vaccine, 0.5 mL IM injection of 1*10^8 Infectious Unit [Inf. U.] once on Day 57.; Biological: Ad26.ZEBOV-Batch #3; Ad26.ZEBOV - Batch #3, live, replication incompetent vaccine, sterile suspension of 0.5 milliliter (mL) intramuscular (IM) injection of 5*10^10 viral particles on Day 1
Experimental: Group 4; Placebo (0.9% saline)- single dose IM injection on Day 1 and Day 57	Biological: Placebo; One 0.5 ml IM injection of 0.9% saline once on Day 1 and Day 57.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Responses to the Study Vaccine Regimens against Ebola virus (EBOV) Glycoprotein (GP) using EBOV GP protein enzyme-linked immunosorbent assay (ELISA)	The humoral immune response will be assessed by enzyme-linked immunosorbent assay (ELISA) binding antibody	At 56 days post prime vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Responses to the Study Vaccine Regimens against Ebola virus (EBOV) Glycoprotein (GP) using EBOV GP protein enzyme-linked immunosorbent assay (ELISA)	The humoral immune response will be assessed by enzyme-linked immunosorbent assay (ELISA) binding antibody	At Days 1, 29 post prime dose and at days 21, 42, and 180 post boost vaccination
Number of Participants with Solicited Local and Systemic Adverse Events (AEs)		Up to 7 days after each vaccination
Number of Participants with Adverse Events (AEs)		Up to 42 days post boost vaccination
Number of Participants with Serious Adverse Events (SAEs)		Continuous throughout the duration of study (Up to 180 Days post boost vaccination)

Collaborators and Investigators

• Sponsor: Crucell Holland BV
• Investigators: Study Director: Crucell Holland BV Clinical Trial, Crucell Holland BV

Publications and helpful links

General Publications

• Bockstal V, Gaddah A, Goldstein N, Shukarev G, Bart S, Luhn K, Robinson C, Anumendem D, Leyssen M, Douoguih M. Assessments of different batches and dose levels of a two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. NPJ Vaccines. 2021 Dec 20;6(1):157. doi: 10.1038/s41541-021-00402-8.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2015
• Primary Completion (Actual): January 22, 2016
• Study Completion (Actual): July 20, 2016

Study Registration Dates

• First Submitted: September 4, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimated): September 7, 2015

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Healthy participants; Ebola viruses; Filoviruses; Monovalent vaccine; Human adenovirus serotype 26 (Ad26) expressing the Ebola virus Mayinga variant glycoprotein (Ad26.ZEBOV); Ebola virus disease (EVD); Modified Vaccinia Virus Ankara - Bavarian Nordic Filo-vector (MVA-BN Filo)
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: CR107786; VAC52150EBL3003 (Other Identifier: Crucell Holland BV)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes