A Phase II Randomised, Controlled Trial to Evaluate the Safety, Immunogenicity and Efficacy of the R21/Matrix-M1 Malaria Vaccine in Healthy African Women of Childbearing Potential in Mali
Overview
- Phase
- Phase 2
- Intervention
- R21/Matrix-M1
- Conditions
- Healthy Women of Child Bearing Potential
- Sponsor
- University of Oxford
- Enrollment
- 330
- Locations
- 1
- Primary Endpoint
- Number of participants with P falciparum infection
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This will be a double-blind, individually randomised trial, to assess the safety, tolerability, immunogenicity, and protective efficacy of two and three doses of the R21/Matrix-M1 malaria vaccine or placebo given at 4 week intervals in healthy women of childbearing potential (WOCBP), who are on pregnancy prevention during vaccination, but report plans to become pregnant in the near future.
Participants will be randomised in Year 1 into three groups in a 1:1:1 ratio:
- Arm 1 (n=110): will receive three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2.
- Arm 2 (n=110): will receive normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at months 1 and 2.
- Arm 3 (n=110): will receive three of doses normal saline (placebo) at months 0, 1 and 2. In Year 2: Non-pregnant participants in arms 1 and 2 will be randomised in a 1:1 ratio to receive a booster dose of R21/Matrix-M1 malaria vaccine or placebo at the beginning of the malaria transmission season. Participants in the control group (arm 3) will receive normal saline (placebo).
Initial follow-up will be for two years after dose three, with an efficacy analysis at 6, 12, 18 and 24 months after dose 3.
Participants will be monitored for safety, tolerability, immunogenicity, and malaria infection during the follow-up period.
Participants will also be monitored for pregnancy over 12 months post primary and booster vaccination and those who become pregnant will be followed during their pregnancy and for 1 year post-delivery (as well as their offspring) for safety and malaria infection
Detailed Description
The design will be a double blind, placebo-controlled study. Malian adult WOCBP between 18 and 35 years of age who consent to participate will be randomised to receive R21/Matrix-M1vaccine or normal saline to assess the safety, immunogenicity and protective efficacy of R21/Matrix-M1 Vaccine. Randomisation and Study Arms Consenting participants who have satisfied all the eligibility criteria and completed the baseline assessment will be individually randomised within the study groups using an electronic randomisation system into three arms in a 1:1:1 ratio. * Arm 1: Participants will receive three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2. * Arm 2: will receive normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at month 1 and 2. * Arm 3: will receive three doses of normal saline (placebo) at months 0, 1 and 2. Participants will be assessed for safety, immunogenicity and efficacy for 12 months. After 12 months non-pregnant participants in arms 1 and 2, will be randomised in a 1:1 ratio; half in each of these two arms will receive a booster dose of R21/Matrix-M1 vaccine and half will receive a placebo injection (normal saline) and be followed up for an additional 12 months. All injections will be administered intramuscularly in the deltoid region, preferably of the non-dominant arm. Post third injection, participants will be followed through the malaria transmission (rainy) season, approximately 6 months, and then the ensuing dry season for an additional 6 months. Participants will be monitored for safety, immunogenicity, and protective efficacy (malaria infection) during the follow-up period. For any women who become pregnant during the two-year period (first year and second year) of the trial, follow up will continue through the end of pregnancy, and any viable newborns/infants and their mothers will be followed through the first year of life.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy females of childbearing potential aged ≥ 18 and ≤ 35 years
- •Able and willing (in the Investigator's opinion) to comply with all study requirements.
- •Agreement to release medical and other information concerning contra-indications for participation in the study, and to be attended by a study clinician for physical examination and any other clinical investigations.
- •Provide written informed consent.
- •Available for the duration of the study
- •Must be willing to use reliable contraception (defined as: pharmacologic contraceptives \[parental delivery\] or pre-existing intrauterine or implantable device) from 21 days prior to study day 1 to 28 days after third vaccination and 21 days prior to the booster vaccination to 28 days after the booster vaccination.
- •Report being interested in becoming pregnant within the next 1 year.
Exclusion Criteria
- •Pregnancy at the time of enrollment, as determined by a positive urine or serum human chorionic gonadotropin (β-hCG) test.
- •Biologically unable to become pregnant secondary to: surgical sterilization, premature ovarian insufficiency (defined as no menses for ≥12 months without an alternative medical cause).
- •Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol.
- •Hemoglobin (Hgb), WBC, absolute neutrophils, and platelets outside the local laboratory-defined limits of normal and ≥ Grade 2 (participants may be included at the investigator's discretion for 'not clinically significant' abnormal values).
- •Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal and ≥ Grade 2 (participants may be included at the investigator's discretion for 'not clinically significant' abnormal values).
- •Infected with human immunodeficiency virus (HIV).
- •Known or documented sickle cell disease by history or lab test at screening (Note: known sickle cell trait is NOT exclusionary).
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- •Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment or during the trial follow up period.
- •Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
Arms & Interventions
Experimental-Standard Regime Malaria Vaccine Group1
Participants receiving three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2.
Intervention: R21/Matrix-M1
Experimental-Standard Regime Malaria Vaccine Group2
Participants receiving normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at month 1 and 2
Intervention: Saline and R21/Matrix-M1
Experimental-Standard Regime Group3
Participants receiving three doses of normal saline (placebo) at months 0, 1 and 2
Intervention: Sterile isotonic (0.9%) normal saline
Outcomes
Primary Outcomes
Number of participants with P falciparum infection
Time Frame: Over 6 months post third vaccination
P. falciparum blood stage infection defined as time to first positive blood smear
Incidence of local and systemic solicited adverse events (AEs)
Time Frame: Within 7 days after each vaccine administration and over 6 months post third vaccination
\- Incidence of local and systemic solicited adverse events (AEs) graded by severity.
Secondary Outcomes
- Anti-CSP antibody concentrations(Through study completion. Timepoints: baseline, days 70, 84, 140, 196, 434, 448, 504 and 560)
- Rate of P.falciparum infection(Over 12-, 18- and 24-months post third vaccination)
- Assessment of safety and tolerabilty(Through study completion, an average of 26 months)
- Rate of P.falciparum infection during pregnancy(Over 9-months pregnancy)