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

Ebola Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04228783
• Other study ID #: CR108694
• Secondary ID: VAC52150EBL3004
• Status: Completed
• Phase: Phase 3
• Start date: February 18, 2020
• Est. completion date: April 25, 2022

Study information

• Verified date: June 2023
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 974
• Est. completion date: April 25, 2022
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Ebola

Intervention

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).
• 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
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).

Locations

Country	Name	City	State
United States	The Center For Pharmaceutical Research	Kansas City	Missouri
United States	AMR New Orleans, Formerly New Orleans Center for Clinical Research - New Orleans, an AMR company	Knoxville	Tennessee
United States	Clinical Research Consortium, an AMR company	Las Vegas	Nevada
United States	Central Kentucky Research Associates, Inc.	Lexington	Kentucky
United States	Coastal Clinical Research, Inc	Mobile	Alabama
United States	Alliance for Multispeciality Research	Norfolk	Virginia
United States	Clinical Research Consortium, an AMR company	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against the Ebola Virus Glycoprotein (EBOV GP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) at 21 Days Post Vaccination 2	Antibody GMCs against the EBOV GP as measured by ELISA at 21 days post Vaccination 2 were reported. GMCs of antibodies binding to EBOV GP using ELISA were reported and were measured in ELISA units per milliliter (EU/mL). Serum samples were collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination. For ELISA binding antibody responses, values below the lower limit of quantification (LLOQ) of 36.11 EU/mL were imputed with half of the LLOQ prior to the computation of the GMCs.	21 Days Post Vaccination 2 (Day 78)
Secondary	Geometric Mean Concentrations (GMCs) of Binding Antibody Levels Against the Ebola Virus Glycoprotein (EBOV GP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) at 56 Days Post Vaccination 1	Antibody GMCs against the EBOV GP as measured by ELISA at 56 days post Vaccination 1 were reported. GMCs of antibodies binding to EBOV GP using ELISA were reported and were measured in ELISA units per milliliter (EU/mL). Serum samples were collected for analysis of binding antibodies against EBOV GP using ELISA to determine humoral responses following vaccination. For ELISA binding antibody responses, values below the LLOQ of 36.11 EU/mL were imputed with half of the LLOQ prior to the computation of the GMCs.	56 Days Post Vaccination 1 (Day 57)
Secondary	Number of Participants With Solicited Local Adverse Events (AEs) Until 7 Days After Vaccination 1 and 2	An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their diary for 7 days post vaccination. Solicited local AEs were injection site pain/tenderness, erythema, induration/swelling, itching, pruritis at the vaccination site.	Until 7 Days after Vaccination 1 on Day 1 (Up to Day 8); Until 7 Days after Vaccination 2 on Day 57 (Up to Day 64)
Secondary	Number of Participants With Solicited Systemic Adverse Events (AEs) Until 7 Days After Vaccination 1 and 2	An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Participants recorded the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement was made on any given day, the highest temperature of that day was recorded in the e-Diary. Fever was defined as endogenous elevation of body temperature greater than or equal to (>=) 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants also noted the signs and symptoms in the e-Diary on a daily basis for 7 days post vaccination 1 and 2 (day of vaccination and the subsequent 7 days), if feasible, for the following events: fatigue, headache, nausea, myalgia, arthralgia, chills, and fever.	Until 7 Days after Vaccination 1 on Day 1 (Up to Day 8); Until 7 Days after Vaccination 2 on Day 57 (Up to Day 64)
Secondary	Number of Participants With Unsolicited Adverse Events (AEs) Until 28 Days After Vaccination 1 and 2	An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary.	Until 28 Days After Vaccination 1 on Day 1 (Up to Day 29); until 28 days after Vaccination 2 on Day 57 (Up to Day 85)
Secondary	Number of Participants With Serious Adverse Events (SAEs)	SAE was any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.	Day 1 up to Day 237 for Groups 1, 2, 3, 4, and up to Day 537 for Groups 5 and 6