Partnership for Research on Ebola Vaccines in Liberia (PREVAIL)

• ClinicalTrials.gov Identifier: NCT02344407
• Recruitment Status: Active, not recruiting
• First Posted: January 26, 2015
• Results First Posted: August 1, 2017
• Last Update Posted: April 15, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information

• First Submitted Date: January 22, 2015
• First Posted Date: January 26, 2015
• Results First Submitted Date: May 25, 2017
• Results First Posted Date: August 1, 2017
• Last Update Posted Date: April 15, 2020
• Study Start Date: January 20, 2015
• Actual Primary Completion Date: June 1, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 3, 2017)

• Serious Adverse Events. [ Time Frame: One month ]
  Number of Participants Experiencing Serious Adverse Events in First 30 Days
• Immunogenicity Measures (ELISA and Neutralization Antigen-specific Assays for Antibody. [ Time Frame: One month ]
  Antibody Response at 1-Month (EU/mL) for Participants Without Elevated Levels at Entry

Original Primary Outcome Measures (submitted: January 22, 2015)

• Adverse events. [ Time Frame: One month ]
• Immunogenicity Measures (ELISA and Neutralization Antigen-specific Assays for Antibody. [ Time Frame: One month ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• 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 Vaccines in Liberia (PREVAIL)
• Official Title: Partnership for Research on Ebola Vaccines in Liberia (PREVAIL)

Brief Summary

Background:

- Ebola virus disease (EVD) affects many people in Liberia and other countries in West Africa. It is caused by the Ebola virus and makes people sick with fever, headache, vomiting, diarrhea, rash, and bleeding. About half the people with EVD die. There is no approved treatment for it. Researchers are studying two Ebola vaccines. The vaccines do not cause Ebola.

Objectives:

- To study the safety and efficacy of two Ebola vaccines.

Eligibility:

- Adults 18 and older who live in Liberia and are at risk for Ebola infection but have never had Ebola.

Design:

• Participants will give information including birthdate, gender, occupation, and location of home. They will give contact information for themselves and 2 alternate contacts. They will give a history of their contact with people with Ebola. Some participants may have a physical. They may have blood taken.
• Participants will be injected with either an Ebola vaccine or a placebo with a needle in the upper arm. The placebo is a salt solution.
• Participants will have blood taken.
• Participants will be watched for 30 minutes.
• Participants will return to the clinic 1 week and 1 month after they get the shot. They will have blood taken.
• After that, participants will be contacted monthly to discuss how they are feeling. They may be contacted by phone, may visit the clinic, or may have a home visit.
• The study ends 8-12 months after participants get the shot. If one of the vaccines works against Ebola and does not have many side effects, participants can get the vaccine if they did not get it in the study.

Detailed Description

Ebola virus disease (EVD) in West Africa is spreading rapidly, and there is a critical need for a vaccine to prevent EVD. There are two candidate Ebola virus vaccines, the chimpanzee adenovirus 3 (ChAd3-EBO Z)-based vaccine and the Vesicular Stomatitis virus (VSVdeltaG-ZEBOV)-based vaccine. This study will evaluate both of these vaccines in a randomized, double-blind, controlled, 3-arm study in Liberia. Each vaccine will be compared against the same active control. Because there are limited data on the safety of these vaccines, the initial phase (phase 2) of the study will include the collection of more detailed data on safety and will define the immune response elicited by each vaccine in the first 600 volunteers. With the decline in new cases of Ebola virus infection the phase 3 component was no longer deemed to be feasible and, following safety, ethical and FDA approve/concurrence, the study was amended to a more robust, 1,500 person phase 2 design.

With the amendment to only a phasae 3 study the endpoint reverted to the phase 2 endpoint of safety and immunogenicity.

Participants aged 18 year and older will be enrolled at health clinics in Monrovia, Liberia over 4 months. A single dose of the assigned agent will be administered. Participants in phase 2 will undergo blood draw and assessment of adverse events (AEs) and signs and symptoms of Ebola infection at 1 week and 1 month after vaccination, and monthly assessment of AEs and signs and symptoms of Ebola thereafter. Participants in phase 3 will undergo monthly assessment of AEs and signs and symptoms of Ebola infection after vaccination. All participants will be followed for 8 to 12 months.

This clinical trial to evaluate vaccine efficacy will provide an accurate assessment of the benefits and risks associated with each candidate vaccine and inform policy on wider scale vaccination in other countries.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Ebola Virus

Intervention

• Biological: VSVG-ZEBOV
  The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)
• Biological: ChAd3-EBO Z
  The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.
• Biological: Placebo

Study Arms

• Experimental: 2
  ChAd3-EBO Z
  Intervention: Biological: ChAd3-EBO Z
• Experimental: 3
  VSVG-ZEBOV
  Intervention: Biological: VSVG-ZEBOV
• Placebo Comparator: 1
  Placebo (Saline)
  Intervention: Biological: Placebo

Publications *

• Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62. doi: 10.1016/S0140-6736(10)60667-8. Review.
• Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa--clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7. doi: 10.1056/NEJMp1413084. Epub 2014 Nov 5.
• Colloca S, Barnes E, Folgori A, Ammendola V, Capone S, Cirillo A, Siani L, Naddeo M, Grazioli F, Esposito ML, Ambrosio M, Sparacino A, Bartiromo M, Meola A, Smith K, Kurioka A, O'Hara GA, Ewer KJ, Anagnostou N, Bliss C, Hill AV, Traboni C, Klenerman P, Cortese R, Nicosia A. Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species. Sci Transl Med. 2012 Jan 4;4(115):115ra2. doi: 10.1126/scitranslmed.3002925.
• Antonello J, Grant-Klein RJ, Nichols R, Kennedy SB, Dubey S, Simon JK. Serostatus cutoff levels and fold increase to define seroresponse to recombinant vesicular stomatitis virus - Zaire Ebola virus envelope glycoprotein vaccine: An evidence-based analysis. Vaccine. 2020 Jun 26;38(31):4885-4891. doi: 10.1016/j.vaccine.2020.04.061. Epub 2020 Jun 1.
• Logue J, Tuznik K, Follmann D, Grandits G, Marchand J, Reilly C, Sarro YDS, Pettitt J, Stavale EJ, Fallah M, Olinger GG, Bolay FK, Hensley LE. Use of the Filovirus Animal Non-Clinical Group (FANG) Ebola virus immuno-assay requires fewer study participants to power a study than the Alpha Diagnostic International assay. J Virol Methods. 2018 May;255:84-90. doi: 10.1016/j.jviromet.2018.02.018. Epub 2018 Feb 23.
• Kennedy SB, Bolay F, Kieh M, Grandits G, Badio M, Ballou R, Eckes R, Feinberg M, Follmann D, Grund B, Gupta S, Hensley L, Higgs E, Janosko K, Johnson M, Kateh F, Logue J, Marchand J, Monath T, Nason M, Nyenswah T, Roman F, Stavale E, Wolfson J, Neaton JD, Lane HC; PREVAIL I Study Group. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017 Oct 12;377(15):1438-1447. doi: 10.1056/NEJMoa1614067.
• Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16;35(35 Pt A):4465-4469. doi: 10.1016/j.vaccine.2017.05.097. Epub 2017 Jun 21.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 17, 2016): 1500
• Original Estimated Enrollment (submitted: January 22, 2015): 28170
• Estimated Study Completion Date: June 1, 2020
• Actual Primary Completion Date: June 1, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:

The inclusion criteria for the study are broad reflecting the target population that would eventually receive an efficacious vaccine.

• Informed consent
• Age greater than or equal to 18 years
• Likely to be in the surrounding area of the vaccination center for at least one year.

EXCLUSION CRITERIA:

• Fever greater than or equal to 38.0 degrees Celsius
• History of EVD (self-report)
• Current pregnancy (a negative urine pregnancy test is required for women of child-bearing potential)
• Breast-feeding an infant
• Any condition which would limit the ability of the participant to meet the requirements of the study protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Liberia

Administrative Information

• NCT Number: NCT02344407
• Other Study ID Numbers: 999915071; 15-I-N071 ( Other Identifier: NIH IRB Protocol ID number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
• Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Not Provided

Investigators

• Principal Investigator: H. Clifford Lane, M.D.; National Institute of Allergy and Infectious Diseases (NIAID)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: February 2020