Assessment of Safety, Immunogenicity and Efficacy of R21/Matrix-M1 Malaria Vaccine in Healthy WOCBP in Mali

NCT06080243 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: VAC 094
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy Women of Child Bearing Potential

Outcome Measures

Primary Outcomes (2)

• Incidence of local and systemic solicited adverse events (AEs)

  \- Incidence of local and systemic solicited adverse events (AEs) graded by severity.

  Within 7 days after each vaccine administration and over 6 months post third vaccination

• Number of participants with P falciparum infection

  P. falciparum blood stage infection defined as time to first positive blood smear

  Over 6 months post third vaccination

Secondary Outcomes (4)

• Assessment of safety and tolerabilty

  Through study completion, an average of 26 months

• Anti-CSP antibody concentrations

  Through study completion. Timepoints: baseline, days 70, 84, 140, 196, 434, 448, 504 and 560

• Rate of P.falciparum infection during pregnancy

  Over 9-months pregnancy

• Rate of P.falciparum infection

  Over 12-, 18- and 24-months post third vaccination

Other Outcomes (9)

• Exploratory - number of participants with negative obstetric outcome

  Over 9-months pregnancy

• Exploratory - Immunology

  Through study completion, an average of 26 months

• Exploratory - Efficacy-Number of participants with symptomatic malaria

  Through study completion, an average of 26 months

Study Arms (3)

Experimental-Standard Regime Malaria Vaccine Group1

ACTIVE COMPARATOR

Participants receiving three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2.

Biological: R21/Matrix-M1

Experimental-Standard Regime Malaria Vaccine Group2

ACTIVE COMPARATOR

Participants receiving normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at month 1 and 2

Biological: Saline and R21/Matrix-M1

Experimental-Standard Regime Group3

ACTIVE COMPARATOR

Participants receiving three doses of normal saline (placebo) at months 0, 1 and 2

Other: Sterile isotonic (0.9%) normal saline

Interventions

Saline and R21/Matrix-M1 BIOLOGICAL

Saline and 10 µg of R21 and 50 µg of Matrix-M1

Also known as: R21/Matrix-M1

Experimental-Standard Regime Malaria Vaccine Group2

R21/Matrix-M1 BIOLOGICAL

10 µg of R21 and 50 µg of Matrix-M1

Experimental-Standard Regime Malaria Vaccine Group1

Sterile isotonic (0.9%) normal saline OTHER

Saline

Also known as: Placebo

Experimental-Standard Regime Group3

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Healthy females of childbearing potential
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• History of hereditary angioedema acquired angioedema, or idiopathic angioedema.
• History of a severe allergic reaction (Grade 2 or higher or per PI discretion) or anaphylaxis following administration of a vaccine.
• Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past two years, or that has required the use of oral or parenteral corticosteroids at any time during the past two years).
• Pre-existing autoimmune or antibody-mediated diseases including but not limited to:
• systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.

Sponsors & Collaborators

• University of Oxford: lead
• Malaria Research and Training Center, Bamako, Mali: collaborator
• European Vaccine Initiative: collaborator

Study Sites (1)

Koumantou Study Clinic

Bougouni, Sikasso, Mali

Location

Related Publications (2)

• Datoo MS, Natama MH, Some A, Traore O, Rouamba T, Bellamy D, Yameogo P, Valia D, Tegneri M, Ouedraogo F, Soma R, Sawadogo S, Sorgho F, Derra K, Rouamba E, Orindi B, Ramos Lopez F, Flaxman A, Cappuccini F, Kailath R, Elias S, Mukhopadhyay E, Noe A, Cairns M, Lawrie A, Roberts R, Valea I, Sorgho H, Williams N, Glenn G, Fries L, Reimer J, Ewer KJ, Shaligram U, Hill AVS, Tinto H. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021 May 15;397(10287):1809-1818. doi: 10.1016/S0140-6736(21)00943-0. Epub 2021 May 5.

  PMID: 33964223 RESULT

• Datoo MS, Natama HM, Some A, Bellamy D, Traore O, Rouamba T, Tahita MC, Ido NFA, Yameogo P, Valia D, Millogo A, Ouedraogo F, Soma R, Sawadogo S, Sorgho F, Derra K, Rouamba E, Ramos-Lopez F, Cairns M, Provstgaard-Morys S, Aboagye J, Lawrie A, Roberts R, Valea I, Sorgho H, Williams N, Glenn G, Fries L, Reimer J, Ewer KJ, Shaligram U, Hill AVS, Tinto H. Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial. Lancet Infect Dis. 2022 Dec;22(12):1728-1736. doi: 10.1016/S1473-3099(22)00442-X. Epub 2022 Sep 7.

  PMID: 36087586 RESULT

MeSH Terms

Interventions

Sodium Chloride; Saline Solution

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Adrian Hill, MD

  University of Oxford

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: October 12, 2023
• Study Start: March 19, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)