Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201712002760250 Date of Approval: 13/11/2017
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Partnership for Research on Ebola VACcination (PREVAC)
Official scientific title Partnership for Research on Ebola VACcination (PREVAC)
Brief summary describing the background and objectives of the trial The purpose of this study is to compare three vaccine strategies with placebo for immunogenicity and safety. The comparisons will be carried out separately for adults and children and for adults and children combined. The three vaccine strategies are: 1) Ad26.ZEBOV (prime) (0.5 mL) followed by an MVA boost (0.5 mL) at 56 days; 2) rVSV (prime) (1 mL) with a placebo (1 mL) boost at 56 days; and 3) rVSV (prime) (1 mL) with a rVSV boost (1 mL) at 56 days.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PREVAC
Disease(s) or condition(s) being studied Ebola,Infections and Infestations
Sub-Disease(s) or condition(s) being studied Ebola
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 31/03/2017
Actual trial start date 31/03/2017
Anticipated date of last follow up 18/06/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 2800
Actual target sample size (number of participants) 2802
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
PREVACEBL3005 LSHTM
2017-001798-18 EUdra CT
C15-33 INSERM
NCT02876328 ClinicalTrials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised For each vaccination center, the randomization schedule will be prepared using block randomization to ensure the desired allocation ratio for the five arms of the study for each vaccination center (2:1:2:1:1). Central randomisation by phone/fax Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Ad26.ZEBOV Vaccine and MVA-BN-Filo Vaccine 0.5 mL intramuscular injection 56 day boost rHAd26 (prime) (0.5 mL) followed by an MVA boost (0.5 mL) at 56 days 800
Control Group Sterile normal saline (sodium chloride 0.9 percent for injection, USP) 0.5 mL intramuscular injection 56 day boost placebo (prime and boost at 56 days) (0.5 mL) 400
Experimental Group rVSV delta-G-ZEBOV-GP Vaccine 1 mL intramuscular injection 56 day boost rVSV (prime) (1 mL) followed by placebo boost (1 mL) at 56 days 800
Experimental Group rVSV delta-G-ZEBOV-GP Vaccine 1 mL intramuscular injection 56 day boost rVSV (prime) (1 mL) followed by rVSV boost (1 mL) at 56 days 400
Control Group Sterile normal saline (sodium chloride 0.9 percent for injection, USP) 1 mL intramuscular injection 56 day boost placebo (prime and boost at 56 days) (1 mL) 400
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
¿ 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 ¿ Fever > 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 < 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 1 Year(s) 99 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/10/2016 The National Research Ethics Board (NREB)
Ethics Committee Address
Street address City Postal code Country
Ministry of Health, Congo Town Monrovia Liberia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 04/11/2016 Institut National de Ia Sante et de Ia Recherche Medicale (INSERM) Ethics Committee (EC)
Ethics Committee Address
Street address City Postal code Country
101, Rue de Tolbiac Paris France
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 22/07/2016 Comité National d¿Ethique pour la Recherche en Santé (CNERS)
Ethics Committee Address
Street address City Postal code Country
Rue du Commerce Conakry Guinea
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 26/02/2018 London School of Hygiene & Tropical Medicine (LSHTM) Research EC
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 11/01/2018 Sierra Leone Ethics and Scientific Review Committee (SLESRC)
Ethics Committee Address
Street address City Postal code Country
Central Medical Stores, New England Ville Freetown Sierra Leone
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 16/04/2018 Faculty of Medicine, Pharmacy, and Odonto-Stomatology (FMPOS) and Institutional Review Board of the University of Maryland
Ethics Committee Address
Street address City Postal code Country
BP 1805 Bamako Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Separately for adults and children: To compare each of the three vaccine strategies with the matched placebo group (3 pair-wise comparisons) for antibody response 12 months after randomization (prime vaccination). In order to facilitate Merck regulatory filings and bridging of immune responses of the rVSVΔG-ZEBOV-GP vaccine from this study to other studies and between pediatric and adult populations, the following objective will be assessed specifically for those in the two rVSVΔG-ZEBOV-GP vaccine groups: • To compare the rVSVΔG-ZEBOV-GP vaccine (pooled rVSVΔG-ZEBOV-GP groups) with the matched placebo group for antibody response 28 days after randomization (prime vaccination). In order to facilitate Janssen regulatory filings of the rHAd26/MVA vaccine, the following objective will be assessed specifically for those in the rHAd26/MVA vaccine group: • To compare the rHAd26/MVA vaccine group with the matched placebo group for antibody response 3 months after randomization (approximately 28 days after the booster vaccination). 12 Months
Secondary Outcome Addressed separately for adults and children: To compare the groups given the Ad26.ZEBOV prime vaccine and the rVSVΔG-ZEBOV-GP prime vaccine (both rVSVΔG-ZEBOV-GP groups combined) each with the pooled placebo group for the antibody response 14 days after randomization (prime vaccination) (immediacy of response). 14 days
Secondary Outcome Addressed separately for adults and children: To compare each of the vaccine groups versus the pooled placebo group for the antibody response profile using measurements at 7, 14, 28, 56, 63 days and at 3, 6 and 12 months after randomization 12 months
Secondary Outcome Addressed separately for adults and children: • To compare each of the vaccine groups with the pooled placebo group for SAEs at 12 months 12 months
Secondary Outcome Addressed separately for adults and children: • To compare the groups given the Ad26.ZEBOV prime vaccine and the rVSVΔG-ZEBOV-GP prime vaccine (both rVSVΔG-ZEBOV-GP groups combined) each with the pooled placebo group for the percent with injection site reactions and AEs graded for severity, including targeted symptoms, during the first week following randomization (including the daily contacts for children only). 1 week
Secondary Outcome • To compare each of the vaccine groups with the pooled placebo group for changes from baseline in biochemical markers and complete blood count (CBC) measurements at 7 days after randomization (children only). 7 days
Secondary Outcome • To compare the rHAd26/MVA and rVSVΔG-ZEBOV-GP boost strategies with the pooled placebo group for changes from baseline in biochemical markers and CBC measurements at 63 days after randomization (children only). 63 days
Secondary Outcome Addressed separately for adults and children: • To compare the rHAd26/MVA and rVSVΔG-ZEBOV-GP boost strategies with the pooled placebo for percent with injection site reactions and AEs graded for severity, including targeted symptoms, immediately following the booster vaccination and through month 3 (approximately 35 days after the booster vaccination). 3 months
Secondary Outcome Addressed separately for adults and children: • To compare the 3 vaccine strategies versus the pooled placebo group for long-term antibody response at 24, 36, 48 and 60 months following randomization. 60 months
Secondary Outcome Addressed separately for adults and children: • To compare the long-term safety at month 24, 36, 48 and 60 following the three vaccine strategies with the pooled placebo group. 60 months
Secondary Outcome Addressed separately for adults and children: • To compare antibody responses and safety outcomes of each of the vaccination strategies versus the pooled placebo group in subgroups defined by age, gender, country, whether the volunteer is a close contact of an Ebola case, the presence of laboratory abnormalities at baseline, and has specific co-morbidities (in particular HIV and nutritional status as measured by body mass index). 60 months
Secondary Outcome For adults and children combined, to compare antibody responses and safety outcomes for each of the vaccination strategies versus placebo. • To carry out operational research which will include ethnographic, participatory and/or qualitative (i.e., focus groups and individual interviews) studies to: 1) identify issues relevant to understanding and acceptability of the trial, the social issues surrounding informed consent, with the primary goal of informing efforts to ensure autonomous fully informed individual consent and assent for minors; 2) describe participants' and caregivers' experience in the trial, and identify barriers and develop solutions to support trial adherence in a culturally sensitive and ethically appropriate way; and 3) understand prevailing representations and affects surrounding the epidemic (including rumors), Ebola and other vaccines, the trial and other relevant phenomena in order to ensure effective communication around the trial. No specific timepoints; they will be developed and implemented throughout the study 0
Secondary Outcome Addressed separately for adults and children: • In a subsample of adults in Guinea, T cell and memory B cell responses for the three vaccine strategies versus placebo will be compared (see Appendix D). Day 14 Day 70 Months 12, 24, 36, 48, 60
Secondary Outcome In a subsample of children, to compare the rVSVΔG-ZEBOV-GP vaccine strategies with the pooled placebo group for shedding of rVSV-ZEBOV-GP RNA, See Appendix E Day 7, 14,28, 56, 63, 3 months
Secondary Outcome Addressed separately for adults and children: • To determine whether exposure to malaria and helminth infections influences the durability of the humoral and cellular immune responses to Ebola vaccines (see Appendix F). Day 0, Months 12, 24, 36,48, 60
Secondary Outcome Addressed separately for adults and children: • To identify multilevel facilitators and barriers to participant retention in PREVAC through retrospective qualitative research with participants after the conclusion of the blinded trial period (first 12 months) (see Appendix G). Month 12
Secondary Outcome Addressed separately for adults and children: • To identify factors that predict participant retention and loss-to-follow-up (LTFU) during the unblinded PREVAC long-term follow-up period (from 12 months up to 5 years) through prospective research (see Appendix G). Months 12, 24,36, 48, 60
Secondary Outcome Addressed separately for adults and children: • To analyze the early vaccine signature, identify early correlates of durable antibody responses and propose in silico methods to optimally allocate vaccine strategies at the individual level. Day 28
Secondary Outcome Addressed separately for adults and children: To compare the groups given the Ad26.ZEBOV prime vaccine and the rVSVΔG-ZEBOV-GP prime vaccine (both rVSVΔG-ZEBOV-GP groups combined) each with the pooled placebo group for percent reporting injection site reactions and AEs graded for severity, including targeted symptoms, following prime vaccination at the vaccination visit, and through 7, 14, and 28 days after the prime vaccination. 28 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Landreah Corniche Nord - en face de l'ambassade du Japon Quartier Landreah Commune Dixinn Conakry Guinea
University Clinical Research Center (UCRC) laboratory Hospital of Point-G Bamako Mali
The Redemption Hospital New Kru Town, Bushrod Island Monrovia Liberia
Centre National de Formation et de Recherche en Sante Rurale de Maferinyah B.P. 2649 Maferinyah Guinea
Mambolo Clinic Mambolo Village Kapesseh Sierra Leone
Centre pour le Development des Vaccins (CVD Djicoroni para, Ex Institut Marchoux, Ministere de la Sante Bamako Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
National Institutes of Health (NIH) Center Drive Bethesda 20892 United States of America
Innovative Medicines Initiative (IMI) IMI2 JU, TO 56, B-1049 Brussels Belgium
EDCTP Anna van Saksenlaan 51 The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor The Liberia-US Clinical Trials Partnership Program, Partnership for Research on Ebola Virus in Liberia Project (PREVAIL) New Kru Town, Bushrod Island Monrovia Liberia Charities/Societies/Foundation
Primary Sponsor National Institute of Allergy and Infectious Diseases (NIAID) 5601 Fishers Lane Bethesda 20892 United States of America Funding Agency
Primary Sponsor Institut National de la Santé et de la Recherche Médicale (INSERM) 101, Rue de Tolbiac Paris France Funding Agency
Primary Sponsor London School of Hygiene and Tropical Medicine(LSHTM) Keppel Street London United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
EUropean CLInical Trials Services Platform & Development (EUCLID) CIC 1401 de Bordeaux, ISPED, Université de Bordeaux, 146 rue Léo Saignat - CS 61292 Bordeaux Cedex 33076 France
Alliance for International Medical Action (ALIMA) 47 Avenue Pasteur Montreuil 93100 France
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Abdoul Habib Beavogui beavoguia_h@yahoo.com +224 628045352 Enta. Fassa
City Postal code Country Position/Affiliation
Conakry 2649 Guinea PI at Landreah and Maferinyah sites
Role Name Email Phone Street address
Principal Investigator Mark Kieh mark.kieh@nih.gov 231 88 052 New Kru Town, Bushrod Island
City Postal code Country Position/Affiliation
Monrovia Liberia Redemption Hospital; PI at Liberia site
Role Name Email Phone Street address
Principal Investigator Bailah Leigh bailahleigh@yahoo.co.uk +23276693102 Dept of Community Health COMAHS Secretariat
City Postal code Country Position/Affiliation
Freetown Sierra Leone PI at Sierra Leone Site
Role Name Email Phone Street address
Principal Investigator Seydou Doumbia sdoumbi@gmail.com 22376461339 UCRC-USTTB
City Postal code Country Position/Affiliation
Bamako Mali PI at UCRC site in Mali
Role Name Email Phone Street address
Principal Investigator Sambo O Sow ssow@som.umaryland.edu 22376348947 Dijcoroni para, Ex Institut Machoux, Minstere de la Sante
City Postal code Country Position/Affiliation
Bamako Mali PI at CVD site in Mali
Role Name Email Phone Street address
Public Enquiries Laurie Doepel ldoepel@niaid.nih.gov 301-435-8595 31 Center Dr, MSC 2520
City Postal code Country Position/Affiliation
Bethesda 20892 United States of America Senior Advisor for Science Communications
Role Name Email Phone Street address
Scientific Enquiries Abdoul Habib Beavogui beavoguia_h@yahoo.com +224 628045352 Enta. Fassa
City Postal code Country Position/Affiliation
Conakry 2649 Guinea PI at Landreah and Maferinyah sites
REPORTING
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