Partnership for Research on Ebola VACcinations (PREVAC)

• ClinicalTrials.gov Identifier: NCT02876328
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2016
• Results First Posted: September 28, 2022
• Last Update Posted: December 8, 2023
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Partnership for Research on Ebola Virus in Liberia (PREVAIL); Institut National de la Santé Et de la Recherche Médicale, France; London School of Hygiene and Tropical Medicine; European and Developing Countries Clinical Trials Partnership (EDCTP)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: August 16, 2016
• First Posted Date: August 23, 2016
• Results First Submitted Date: July 14, 2022
• Results First Posted Date: September 28, 2022
• Last Update Posted Date: December 8, 2023
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: December 24, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2022)

Percentage of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response [ Time Frame: Measured through Month 12 ]

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.

• Original Primary Outcome Measures (submitted: August 18, 2016): Number of participants with Ebola virus glycoprotein (GP-EBOV) antibody response [ Time Frame: Measured through Month 12 ]

Current Secondary Outcome Measures (submitted: July 14, 2022)

• Frequency of Serious Adverse Events (SAEs) [ Time Frame: Measured through Month 60 ]
  SAEs as defined in the protocol
• Number of Participants With Ebola Virus Glycoprotein (GP-EBOV) Antibody Response [ Time Frame: Measured through Month 60 ]
  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.

• Original Secondary Outcome Measures (submitted: August 18, 2016): Frequency of serious adverse events (SAEs) [ Time Frame: Measured through Month 12 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Partnership for Research on Ebola VACcinations
• Official Title: Partnership for Research on Ebola VACcinations (PREVAC)
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Ebola Virus Disease

Intervention

• 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 Name: 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
• 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: 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: 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:

  • rVSVΔG-ZEBOV-GP
  • rVSV
  • V920

Study Arms

• 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.
  Interventions:

  • Biological: Ad26.ZEBOV
  • Biological: MVA-BN-Filo
• Placebo Comparator: Placebo (0.5 mL)
  Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.
  Intervention: Biological: Placebo
• 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.
  Interventions:

  • Biological: rVSVΔG-ZEBOV-GP
  • Biological: Placebo
• 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.
  Interventions:

  • Biological: rVSVΔG-ZEBOV-GP
  • Biological: rVSV boost
• Placebo Comparator: Placebo (1 mL)
  Participants will receive placebo at Day 0 followed by a placebo boost at Day 56.
  Intervention: Biological: Placebo

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 21, 2019): 4789
• Original Estimated Enrollment (submitted: August 18, 2016): 4900
• Estimated Study Completion Date: June 2024
• Actual Primary Completion Date: December 24, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Guinea, Liberia, Mali, Sierra Leone

Administrative Information

• NCT Number: NCT02876328
• Other Study ID Numbers: C15-33; PREVACEBL3005 ( Other Identifier: LSHTM )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current

Collaborators

• Partnership for Research on Ebola Virus in Liberia (PREVAIL)
• Institut National de la Santé Et de la Recherche Médicale, France
• London School of Hygiene and Tropical Medicine
• European and Developing Countries Clinical Trials Partnership (EDCTP)

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

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: December 2023