A Study of 2-dose Vaccine Regimen Using 3 Consecutive Lots of Ad26.ZEBOV and MVA-BN-Filo in Adult Participants

• ClinicalTrials.gov Identifier: NCT04228783
• Recruitment Status: Completed
• First Posted: January 14, 2020
• Last Update Posted: June 8, 2022
• Sponsor: Janssen Vaccines & Prevention B.V.
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Study Description

Brief Summary:

The purpose of this study is to demonstrate that the paired 2-dose vaccine regimens from 3 consecutively manufactured lots of Adenovirus serotype 26 encoding the Ebola virus Mayinga glycoprotein (Ad26.ZEBOV) as Dose 1 and 3 consecutively manufactured lots of Modified Vaccinia Ankara Bavarian Nordic vector encoding multiple filovirus proteins (MVA-BN-Filo) including the ebola virus mayinga glycoprotein as Dose 2, administered at a 56-day interval, induce an equivalent humoral immune response.

Condition or disease	Intervention/treatment	Phase
Ebola	Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 974 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety, Reactogenicity, and Consistency of a Heterologous 2-dose Vaccine Regimen Using 3 Consecutive Lots of Ad26.ZEBOV and MVA-BN®-Filo in Adult Participants
• Actual Study Start Date: February 18, 2020
• Actual Primary Completion Date: April 25, 2022
• Actual Study Completion Date: April 25, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Active Vaccine: Group 1 (Ad26.ZEBOV-Lot A, MVA-BN-Filo-Lot 1); Participants will receive Intramuscular injection (0.5 milliliter [mL]) of Adenovirus serotype 26 encoding the Ebola virus Mayinga glycoprotein (Ad26.ZEBOV) as Dose 1 (5*10^10 viral particle(s) [vp], Lot A) on Day 1, followed by Modified Vaccinia Ankara Bavarian Nordic vector encoding multiple filovirus proteins (MVA-BN-Filo) as Dose 2 (1*10^8 infectious unit(s) [Inf U], Lot 1) on Day 57.	Biological: Ad26.ZEBOV; Participants will receive IM injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot A, B, and C) on Day 1 (Groups 1, 2, 3 and 5) and an Ad26.ZEBOV booster dose on Day 177 (Group 5).; Biological: MVA-BN-Filo; Participants will receive IM injection (0.5 mL) of MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 1, 2, 3 and 5) on Day 57.
Experimental: Active Vaccine: Group 2 (Ad26.ZEBOV-Lot B, MVA-BN-Filo-Lot 2); Participants will receive Intramuscular injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot B) on Day 1, followed by MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 2) on Day 57.	Biological: Ad26.ZEBOV; Participants will receive IM injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot A, B, and C) on Day 1 (Groups 1, 2, 3 and 5) and an Ad26.ZEBOV booster dose on Day 177 (Group 5).; Biological: MVA-BN-Filo; Participants will receive IM injection (0.5 mL) of MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 1, 2, 3 and 5) on Day 57.
Experimental: Active Vaccine: Group 3 (Ad26.ZEBOV-Lot C, MVA-BN-Filo-Lot 3); Participants will receive Intramuscular injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot C) on Day 1, followed by MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 3) on Day 57.	Biological: Ad26.ZEBOV; Participants will receive IM injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot A, B, and C) on Day 1 (Groups 1, 2, 3 and 5) and an Ad26.ZEBOV booster dose on Day 177 (Group 5).; Biological: MVA-BN-Filo; Participants will receive IM injection (0.5 mL) of MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 1, 2, 3 and 5) on Day 57.
Placebo Comparator: Control Vaccine: Group 4 (Placebo); Participants will receive Intramuscular injection (0.5 mL) of placebo (0.9 percent [%] saline) matching to Ad26.ZEBOV as Dose 1 on Day 1, followed by placebo matching to MVA-BN-Filo as Dose 2 on Day 57.	Biological: Placebo; Participants will receive IM injection (0.5 mL) of placebo (0.9 % saline) as Dose 1 on Day 1, followed by placebo as Dose 2 on Day 57 (Groups 4 and 6) and a booster of matching placebo on Day 177 (Group 6).
Experimental: Booster Cohort: Group 5 (Ad26.ZEBOV, MVA-BN-Filo, Ad26.ZEBOV); Participants will receive Intramuscular injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, a single Lot) on Day 1, followed by MVA-BN-Filo as Dose 2 (1*10^8 Inf U, a single Lot) on Day 57 and a booster dose of Ad26.ZEBOV (at a dose of 5*10^10 vp, a single Lot) 4 months after Dose 2 (on Day 177).	Biological: Ad26.ZEBOV; Participants will receive IM injection (0.5 mL) of Ad26.ZEBOV as Dose 1 (5*10^10 vp, Lot A, B, and C) on Day 1 (Groups 1, 2, 3 and 5) and an Ad26.ZEBOV booster dose on Day 177 (Group 5).; Biological: MVA-BN-Filo; Participants will receive IM injection (0.5 mL) of MVA-BN-Filo as Dose 2 (1*10^8 Inf U, Lot 1, 2, 3 and 5) on Day 57.
Placebo Comparator: Booster Cohort: Group 6 (Placebo); Participants will receive Intramuscular injection (0.5 mL) of placebo (0.9% saline) matching to Ad26.ZEBOV as Dose 1 on Day 1, followed by placebo matching to MVA-BN-Filo as Dose 2 on Day 57 and a booster dose of matching placebo on Day 177.	Biological: Placebo; Participants will receive IM injection (0.5 mL) of placebo (0.9 % saline) as Dose 1 on Day 1, followed by placebo as Dose 2 on Day 57 (Groups 4 and 6) and a booster of matching placebo on Day 177 (Group 6).

Outcome Measures

Primary Outcome Measures :

1. Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Day 78 (21 days post Dose 2) ]
   Serum concentration of antibodies binding to EBOV GP using ELISA will be reported. Serum samples will be collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination.

Secondary Outcome Measures :

1. Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Day 57 (56 days post Dose 1) ]
   Serum concentration of antibodies binding to EBOV GP measured using ELISA will be reported. Serum samples will be collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination.
2. Number of Participants with Solicited Local and Systemic Adverse Events (AEs) [ Time Frame: 7 days after each vaccination (up to Day 64) ]
   Number of participants with solicited local and systemic adverse events (AEs) will be reported. Following solicited local AEs are: pain/tenderness, erythema, induration/swelling, and pruritus and solicited systemic AEs are: fatigue, headache, nausea, myalgia, arthralgia, chills, and fever.
3. Number of Participants with Unsolicited AEs [ Time Frame: 28 days after each vaccination (up to Day 85) ]
   Number of participants with unsolicited AEs will be evaluated. Unsolicited AEs will include all AEs for which the participant is not specifically questioned in the participant diary. Unsolicited AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2) and severe (Grade 3).
4. Number of Participants with Serious AEs [ Time Frame: Up to Day 237 ]
   A serious AE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important to prevent one of the outcomes listed above.

Other Outcome Measures:

1. Binding Antibody Levels Against Ebola Virus Glycoprotein (EBOV GP) Measured Using Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Days 177, 184, 198, 357 and 537 ]
   Serum concentration of antibodies binding to EBOV GP using ELISA will be reported. Serum samples will be collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination.
2. Number of Participants with Solicited Local and Systemic Adverse Events (AEs) [ Time Frame: 7 days post booster vaccination (up to Day 184) ]
   Number of participants with solicited local and systemic adverse events (AEs) will be reported. Following solicited local AEs are: pain/tenderness, erythema, induration/swelling, and pruritus and solicited systemic AEs are: fatigue, headache, nausea, myalgia, arthralgia, chills, and fever.
3. Number of Participants with Unsolicited AEs [ Time Frame: 28 days post booster vaccination (up to Day 205) ]
   Number of participants with unsolicited AEs will be evaluated. Unsolicited AEs will include all AEs for which the participant is not specifically questioned in the participant diary. Unsolicited AEs will be graded according to severity as mild (Grade 1), moderate (Grade 2) and severe (Grade 3).
4. Number of Participants with Serious AEs [ Time Frame: Up to Day 537 ]
   A serious AE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important to prevent one of the outcomes listed above.
5. Viral Neutralizing Antibody Levels Against the Ad26.ZEBOV [ Time Frame: Baseline (Day 1), Day 177 and Day 198 ]
   Viral neutralizing antibody levels against the Ad26.ZEBOV will be reported. Blood samples will be collected for analysis of viral neutralizing antibodies against Ad26 vector.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Signed an informed consent form (ICF)
• Medically stable in the investigator's clinical judgment on the basis of physical examination, medical history, and vital signs performed at screening
• Before randomization, a woman must be either: a. Not of childbearing potential; b. Of childbearing potential and practicing an acceptable effective method of birth control and agrees to remain on such a method of birth control from signing the informed consent form (ICF) until at least 3 months post Dose 1 vaccination or 28 days post Dose 2 vaccination or 3 months post booster vaccination (Groups 5-6 only), whichever comes later. Use of hormonal contraception should start at least 28 days before the first administration of study vaccine. Acceptable effective methods for this study include: 1) hormonal contraception; 2) intrauterine device (IUD); 3) intrauterine hormone-releasing system (IUS); 4) male or female condom with or without spermicide; 5) cap, diaphragm, or sponge with a vaginal spermicide; 6) vasectomized partner (the vasectomized partner should be the sole partner for that participant); 7) sexual abstinence
• Women of childbearing potential must have a negative urine Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test at screening and immediately prior to each study vaccine administration
• Available and willing to participate for the duration of the study and follow-up visit
• Willing to provide verifiable identification

Exclusion Criteria:

• Having received any candidate Ebola vaccine
• Diagnosed with Ebola virus disease (EVD), or prior exposure to Ebola virus, including travel to an area with Ebola outbreak less than 1 month prior to screening (if applicable)
• 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 (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0ºCelcius on Day 1. Participants with such symptoms will be excluded from enrollment at that time but may be rescheduled for enrollment at a later date
• Human immunodeficiency virus (HIV) type 1 or type 2 infection, based on the medical history reported by the participant
• Pregnant, breast-feeding
• History of an underlying clinically significant acute or chronic medical condition

Contacts and Locations

Locations

United States, Alabama

Coastal Clinical Research, Inc

Mobile, Alabama, United States, 36608

United States, Arizona

Clinical Research Consortium, an AMR company

Tempe, Arizona, United States, 85283

United States, Kentucky

Central Kentucky Research Associates, Inc.

Lexington, Kentucky, United States, 40509

United States, Missouri

The Center For Pharmaceutical Research

Kansas City, Missouri, United States, 64114

United States, Nevada

Clinical Research Consortium, an AMR company

Las Vegas, Nevada, United States, 89119

United States, Tennessee

AMR New Orleans, Formerly New Orleans Center for Clinical Research - New Orleans, an AMR company

Knoxville, Tennessee, United States, 37920

United States, Virginia

Alliance for Multispeciality Research

Norfolk, Virginia, United States, 23502

Sponsors and Collaborators

Janssen Vaccines & Prevention B.V.

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: NCT04228783
• Other Study ID Numbers: CR108694; VAC52150EBL3004 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
• First Posted: January 14, 2020
• Last Update Posted: June 8, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

• URL: https://www.janssen.com/clinical-trials/transparency

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