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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201907491834482 Date of Registration: 02/07/2019
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A randomized controlled Phase 3 trial to assess the safety, immunogenicity and efficacy of a trivalent rotavirus P2-VP8 subunit vaccine in prevention of severe rotavirus gastroenteritis in healthy infants in Africa and India
Official scientific title A Phase 3 double-blind, randomized, active comparator-controlled, group-sequential, multinational trial to assess the safety, immunogenicity and efficacy of a trivalent rotavirus P2-VP8 subunit vaccine in prevention of severe rotavirus gastroenteritis in healthy infants
Brief summary describing the background and objectives of the trial Live oral rotavirus vaccines have not performed as well in resource limited populations as in developed countries. Clinical testing of the trivalent rotavirus P2-VP8 subunit vaccine has demonstrated the vaccine to be well-tolerated, without safety signals. The trivalent vaccine is an intramuscular injection. it includes antigens from the 3 P-types responsible for the vast majority of global rotavirus disease burden, has been developed to maximize impact in developing world populations. Should this trial demonstrate improved efficacy in comparison to a currently licensed live, oral vaccine, the intention is to obtain licensure and WHO prequalification, allowing for the distribution of an inexpensive and readily manufactured vaccine to those populations in resource limited settings most critically in need of a more efficacious vaccine than the currently available vaccines.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Rotavirus
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 29/07/2019
Actual trial start date 10/10/2019
Anticipated date of last follow up 15/12/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 8200
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
CVIA 061 PATH
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 Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Trivalent subunit vaccine P2 VP8 Investigational group will receive 90 ug trivalent subunit vaccine (TV P2-VP8) as 0.5 ml intramuscular injection (IM) to anterolateral thigh at 6 weeks, 10 weeks, and 14 weeks (same as EPI schedule) with oral placebo. Oral placebo is a colorless oral rehydration solution that follows WHO recommendations. 1.5 ml will be administered by mouth at 6 weeks and 10 weeks (same as Rotarix schedule). Three doses TV P2-VP8 IM plus oral placebo administered at monthly intervals starting at ≥6 to <8 weeks of age, administered concomitantly with EPI/UIP vaccines. Blood will be collected from infants at two time points: first time is before the first vaccination and the second is 28 days after the third injection. All participants will be monitored weekly for gastroenteritis until 24 months of age. Trivalent rotavirus VP8 subunit, tetanus toxin P2 epitope, fusion proteins adsorbed to aluminum hydroxide adjuvant. The trivalent rotavirus P2-VP8 subunit vaccine produced in E. coli is adsorbed onto aluminum hydroxide (0.5625 mg/dose). Each 0.5 mL dose, to be administered intramuscularly, contains 30 μg of each of the three antigens (derived from a P [4], a P [6] and a P [8] strain of rotavirus), for a total of 90 μg of subunit protein. The three antigens are derived from DS1, 1076 and Wa strains, respectively. 4100
Control Group Rotarix Two oral doses, one on Day 1 and Day 29 or 6 weeks and 10 weeks, same as EPI for Rotarix. Placebo injection (IM) will be 0.5 ml saline (NaCl 0.9%) USP administered at 6,10, and 14 weeks. Two doses of Rotarix® plus IM placebo at monthly intervals starting at ≥6 to <8 weeks of age, administered concomitantly with EPI/UIP vaccines until Day 57 (14 weeks) Rotarix® (Rotavirus Vaccine, Live, Oral), for oral administration, is a live, attenuated rotavirus vaccine derived from the human 89-12 strain which belongs to G1P[8] type. 4100 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Healthy infants as established by medical history and clinical examination before randomization into the study Age: ≥6 and <8 weeks at the time of first study vaccination (42 days through 55 days old, inclusive, with the day after birth considered 1-day old) Parental ability and willingness to provide written informed consent Intention of the participants’ parents to remain in the area with the child during the study period Acute disease at the time of enrollment/first study vaccination - temporary exclusion Presence of fever on the day of enrollment/first study vaccination (axillary temperature >37.6C) - temporary exclusion Concurrent participation in another clinical trial throughout the entire timeframe for this study (participation in non-interventional observational study is allowed if there is no blood draw) Presence of severe malnutrition (weight-for-height z-score ≤-3SD median (per WHO published child growth standards) or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant’s health or is likely to result in nonconformance to the protocol History of premature birth (<37 weeks gestation) and/or birth weight of <2.5 kg History of congenital abdominal disorders, intussusception, or abdominal surgery Prior receipt of rotavirus vaccine Known sensitivity or allergy to any components of the study vaccine Contraindications to any of the EPI/UIP vaccines History of anaphylactic reaction Major congenital or genetic defect Parents not able, available or willing to accept active weekly follow-up by the study staff Receipt of any immunoglobulin therapy and/or blood products History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (those on inhaled or topical steroids may be permitted to participate in the study) Any medical condition in the participant or parents that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a parents’ ability to give informed consent Exclusion of nursing infants whose mothers are receiving immunosuppressive biologics Infant: 13 Month(s)-24 Month(s) 6 Week(s) 8 Week(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 20/09/2019 University of Zambia Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus Lusaka 50110 Zambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 06/06/2019 Noguchi Memorial Institute for Medical Research Institutional Review Board
Ethics Committee Address
Street address City Postal code Country
P.O. Box LG 581 Legon Accra 23321 Ghana
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Laboratory confirmed cases of Severe Rotavirus Gastroenteritis - SVRGE (any strain) With onset at least 2 weeks after receipt of third study vaccination
Primary Outcome Serious adverse events (SAEs), including intussusception Through 28 days after the last dose of study vaccine
Primary Outcome Adverse Events - AEs >grade 2 Through 28 days after the last dose of study vaccine
Secondary Outcome Laboratory confirmed cases of VSRVGE - any strain 2 weeks after receipt of 3rd study vaccination and onset at any time
Secondary Outcome P-type specific laboratory confirmed cases of SRVGE and VSRGE 2 weeks after receipt of 3rd study vaccination and onset at any time
Secondary Outcome Laboratory confirmed cases of rotavirus gastroenteritis of any strain of any severity 2 weeks after receipt of 3rd study vaccination and onset at any time
Secondary Outcome Laboratory confirmed cases of hospitalized for RVGE any severity 2 weeks after receipt of 3rd study vaccination and onset at any time
Secondary Outcome Incidence of SRVGE and VSRVGE per 100 children-years 2 weeks after receipt of 3rd study vaccination and onset at any time
Secondary Outcome Solicited local and systemic AEs Immediately following and during the 7 days after each vaccination in the reactogenicity cohort
Secondary Outcome SAEs, including intussusception Throughout the duration of the study
Secondary Outcome Anti-P2-VP8 IgA and IgG seroresponse rates by ELISA in assays using each of the three vaccine antigens Baseline and 28 days post-third vaccination
Secondary Outcome Neutralizing antibody seroresponse rates to each of the three rotavirus strains from which the vaccine antigens are derived Baseline and 28 days post-third study vaccination
Secondary Outcome Anti-P2-VP8 IgA and IgG geometric mean titers and geometric mean fold rises in ELISA assays using each of the three vaccine antigens Baseline and 28 days post-third study vaccination
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre for Infectious Disease Research in Zambia Plot 34620 Off Alick Nkhata Road, Mass Media, P.O. Box 34681 Lusaka Zambia
Dodowa Health Research Centre Box DD1 Dodowa Ghana
Malawi Liverpool Wellcome Trust Clinical Research Programme Queen Elizabeth Central Hospital College of Medicine, P.O. Box 30096 Chichiri Blantyre 3 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 Fifth Avenue North Seattle 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor PATH 455 Massachusetts Ave Washington DC 20001 United States of America Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
SK Bioscience ECO Hub 332 Gyeonggi do 13493 Korea, Democratic People's Republic of
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Caroline Chisenga Caroline.Chisenga@cidrz.org 0978526864 Plot 34620 Off Alick Nkhata Road, Mass Media, P.O. Box 34681
City Postal code Country Position/Affiliation
Lusaka Zambia Post Doctoral Research Fellow
Role Name Email Phone Street address
Principal Investigator Alberta Amu alberta.amu@gmail.com 0244755358 P.O. Box LG 581
City Postal code Country Position/Affiliation
Accra Ghana Physician
Role Name Email Phone Street address
Principal Investigator Desiree Witte Desiree.Witte@liverpool.ac.uk 2651874628 P.O. Box 30096 Chichiri
City Postal code Country Position/Affiliation
Blantyre 3 Malawi Physician
Role Name Email Phone Street address
Public Enquiries Elayna Oberman eoberman@path.org 2062853500 2201 Westlake Avenue, Suite 200
City Postal code Country Position/Affiliation
Seattle United States of America Communications
Role Name Email Phone Street address
Scientific Enquiries Tushar Tewari ttewari@path.org 911140640000 15th Floor, Dr. Gopal Das Bhawan 28, Barakhamba Road Connaught Place
City Postal code Country Position/Affiliation
New Delhi 110001 India Medical Officer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results for primary and secondary objectives. Statistical Analysis Plan,Study Protocol Within 12 months of completion of study Researchers who provide a methodologically sound proposal may be provided access after Sponsor permission.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information