Partnership for Research on Ebola VACcinations (PREVAC)

Partnership for Research on Ebola VACcinations (PREVAC)

The purpose of this study is to evaluate the safety and immunogenicity of three vaccine strategies that may prevent Ebola virus disease (EVD) events in children and adults. Participants will receive either the Ad26.ZEBOV (rHAd26) vaccine with a MVA-BN-Filo (MVA) boost, or the rVSVΔG-ZEBOV-GP (rVSV) vaccine with or without boosting, or placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Ebola Virus Disease
• Intervention / Treatment: Biological: Ad26.ZEBOV; Biological: MVA-BN-Filo; Biological: Placebo; Biological: rVSVΔG-ZEBOV-GP; Biological: rVSV boost

Detailed Description

The purpose of this study is to evaluate the safety and immunogenicity of two Ebola virus disease (EVD) vaccines, Ad26.ZEBOV (rHAd26) and rVSVΔG-ZEBOV-GP (rVSV), in children and adults. These vaccines will be studied using three different strategies: the rHAd26 vaccine plus a MVA-BN-Filo (MVA) boost, and the rVSV vaccine with or without boosting.

Participants will be randomized into five groups: the Ad26.ZEBOV vaccine with an MVA boost, the rVSV vaccine with or without boosting, or one of two placebo groups. At Day 0 (study entry), participants will receive the Ad26.ZEBOV vaccine, the rVSV vaccine, or placebo.

At Day 56, participants assigned to the rVSV vaccine without a boost and the two placebo groups will receive placebo. Those initially given the Ad26.ZEBOV vaccine will receive the MVA boost. Those assigned to the boosted rVSV group will receive the rVSV boost.

Additional study visits will occur on Days 7, 14, 28, and 63, and at Months 3, 6, 12, 24, 36, 48, and 60. Study visits may include blood collection and other assessments.

Some participants may take part in substudies, which will include blood or saliva collection.

After the Month 12 visit, during the long-term follow-up, the participants who received the placebo will be vaccinated with a single dose of rVSVΔG-ZEBOV-GP vaccine in Liberia and Mali and with the Ad26.ZEBOV/MVA-BN-Filo vaccine strategy in Guinea and Sierra Leone. The participants who received an incomplete Ad26.ZEBOV/MVA-BN-Filo vaccine strategy will be offered a single dose of the Ad26.ZEBOV or MVA-BN-Filo vaccine in Guinea and Sierra Leone and a single dose of rVSVΔG-ZEBOV-GP in Liberia and Mali.

• Study Type: Interventional
• Enrollment (Actual): 4789
• Phase: Phase 2

Contacts and Locations

Study Locations

• Guinea
  • Conakry, Guinea
    • Centre national de formation et de recherche en santé rurale (Maferyniah)
  • Conakry, Guinea
    • Landreah
• Liberia
  • Monrovia, Liberia
    • The Redemption Hospital
• Mali
  • Bamako, Mali
    • Centre pour le Développement des Vaccins (CVD)
  • Bamako, Mali
    • University Clinical Research Center (UCRC)
• Sierra Leone
  • Kapesseh, Sierra Leone
    • Mambolo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Informed consent/assent
• Age greater than or equal to 1 year
• Planned residency in the area of the study site for the next 12 months
• Willingness to comply with the protocol requirements

Exclusion Criteria:

• Fever greater than 38º Celsius
• History of EVD (self-report)
• Pregnancy (a negative urine pregnancy test is required for females of child-bearing potential, i.e., females who have experienced menarche or who are aged 14 years and older)
• Positive HIV test for participants less than 18 years of age
• Reported current breast-feeding
• Prior vaccination against Ebola (self-report)
• Any vaccination in the past 28 days or planned within the 28 days after randomization (initial vaccination)
• In the judgement of the clinician, any clinically significant acute/chronic condition that would limit the ability of the participant to meet the requirements of the study protocol

Inclusion Criteria for Revaccination Post 12 Month Visit:

• Participants who received the placebo
• Participants who received an incomplete Ad26.ZEBOV/MVA-BN-Filo vaccine strategy

Temporary Exclusion Criteria for Revaccination Post 12 Month Visit:

• Fever greater than 38º Celsius
• Pregnancy (a negative urine pregnancy test is required for females of child-bearing potential, i.e., females who have experienced menarche or who are aged 14 years and older)
• Reported current breast-feeding (self-report)
• Any vaccination in the past 28 days or planned within the 28 days after trial vaccination

Exclusion Criteria for Revaccination Post 12 Month Visit:

• EVD notified in the electronic case report form
• For minor participants: change in HIV status since enrollment (self-report)
• Previous Ebola vaccination outside of the study including incomplete vaccine strategies
• Known medical history or significant risk factors for a thrombotic and/or thrombocytopenic event (for participants who will receive the Ad26.ZEBOV or MVA-BN-Filo vaccine)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad26.ZEBOV (rHAd26) vaccine + MVA-BN-Filo (MVA) boost; Participants will receive the Ad26.ZEBOV (rHAd26) vaccine at Day 0 followed by an MVA-BN-Filo (MVA) boost at Day 56.	Biological: Ad26.ZEBOV; 0.5 mL at a dose of 5x10^10 vp administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Other Names: rHAd26; Biological: MVA-BN-Filo; 0.5 mL at a dose of 1x10^8 InfU administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Other Names: MVA; MVA-mBN226B
Placebo Comparator: Placebo (0.5 mL); Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.	Biological: Placebo; 0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children
Experimental: rVSVΔG-ZEBOV-GP (rVSV) vaccine + placebo boost; Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by a placebo boost at Day 56.	Biological: Placebo; 0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Biological: rVSVΔG-ZEBOV-GP; 1 mL at a nominal dose of 2x10^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Other Names: rVSV; V920
Experimental: rVSVΔG-ZEBOV-GP (rVSV) vaccine + rVSV boost; Participants will receive the rVSVΔG-ZEBOV-GP (rVSV) vaccine at Day 0 followed by an rVSV boost at Day 56.	Biological: rVSVΔG-ZEBOV-GP; 1 mL at a nominal dose of 2x10^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Other Names: rVSV; V920; Biological: rVSV boost; 1 mL at a nominal dose of 2x10^7 pfu/mL administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children; Other Names: rVSV; V920; rVSVΔG-ZEBOV-GP
Placebo Comparator: Placebo (1 mL); Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.	Biological: Placebo; 0.5 mL or 1 mL (depending upon the arm) sterile normal saline administered by intramuscular (IM) injection into the upper arm for adults or the thigh for children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response	Antibody responder at 12 months is defined as a participant who experiences a 4-fold increase in antibody level from baseline and for whom the antibody level at 12 months is greater than or equal to 200 EU/mL.	Measured through Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Serious Adverse Events (SAEs)	SAEs as defined in the protocol	Measured through Month 60
Number of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response	Antibodies to the Ebola virus glycoprotein will be measured with the Filovirus Animal Nonclinical Group (FANG) ELISA assay if available. Other assays may also be used.	Measured through Month 60

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: London School of Hygiene and Tropical Medicine; Institut National de la Santé Et de la Recherche Médicale, France; European and Developing Countries Clinical Trials Partnership (EDCTP); Partnership for Research on Ebola Virus in Liberia (PREVAIL)
• Investigators: Principal Investigator: Yazdan Yazdanpannah, Institut National de la Santé Et de la Recherche Médicale, France; Principal Investigator: Abdoul Habib Beavogui, Centre de Formation et de Recherche en Santé Rurale de Mafèrinyah; Principal Investigator: Mark Kieh, Redemption Hospital; Principal Investigator: Bailah Leigh, University of Sierra Leone; Principal Investigator: Stephen B. Kennedy, Redemption Hospital; Principal Investigator: Seydou Doumbia, University of Sciences, Techniques and Technologies of Bamako; Principal Investigator: Samba O. Sow, Centre pour le Developpement des Vaccins

Publications and helpful links

General Publications

• Badio M, Lhomme E, Kieh M, Beavogui AH, Kennedy SB, Doumbia S, Leigh B, Sow SO, Diallo A, Fusco D, Kirchoff M, Termote M, Vatrinet R, Wentworth D, Esperou H, Lane HC, Pierson J, Watson-Jones D, Roy C, D'Ortenzio E, Greenwood B, Chene G, Richert L, Neaton JD, Yazdanpanah Y; PREVAC study team. Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries. Trials. 2021 Jan 23;22(1):86. doi: 10.1186/s13063-021-05035-9. Erratum In: Trials. 2021 Sep 1;22(1):583.
• PREVAC Study Team; Kieh M, Richert L, Beavogui AH, Grund B, Leigh B, D'Ortenzio E, Doumbia S, Lhomme E, Sow S, Vatrinet R, Roy C, Kennedy SB, Faye S, Lees S, Millimouno NP, Camara AM, Samai M, Deen GF, Doumbia M, Esperou H, Pierson J, Watson-Jones D, Diallo A, Wentworth D, McLean C, Simon J, Wiedemann A, Dighero-Kemp B, Hensley L, Lane HC, Levy Y, Piot P, Greenwood B, Chene G, Neaton J, Yazdanpanah Y. Randomized Trial of Vaccines for Zaire Ebola Virus Disease. N Engl J Med. 2022 Dec 29;387(26):2411-2424. doi: 10.1056/NEJMoa2200072. Epub 2022 Dec 14.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): December 24, 2019
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (Estimated): August 23, 2016

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Ebola Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Virus Diseases; Hemorrhagic Fever, Ebola; Anti-Infective Agents; Antiviral Agents; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: C15-33; PREVACEBL3005 (Other Identifier: LSHTM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No