Healthy Women of Child Bearing PotentialPhase 2NCT06080243
Assessment of Safety, Immunogenicity and Efficacy of R21/Matrix-M1 Malaria Vaccine in Healthy WOCBP in Mali
A Phase 2 study testing R21/Matrix-M1, Saline and R21/Matrix-M1 and Sterile isotonic (0.9%) normal saline in people with Healthy Women of Child Bearing Potential, run by University of Oxford at 1 site in Mali.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Women of Child Bearing Potential
- What is being tested?
- R21/Matrix-M1, Saline and R21/Matrix-M1 and Sterile isotonic (0.9%) normal saline
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 1 siteMali
- Study dates
- 19 Mar 2025to 31 Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
- 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.
- Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia; recurrent, severe infections and chronic (more than 14 days) systemically active immunosuppressant medication within the past 6 months.
- Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone ≥20 mg/day) or immunosuppressive drugs within 30 days of vaccination.
- Receipt of a live vaccine within the past 28 days or a killed vaccine within the past 14 days prior to Vaccination #1 and every subsequent vaccination day.
- Receipt of immunoglobulins and/or blood products within the past six months.
- Previous receipt of an investigational malaria vaccine in the last five years.
- Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or would render the participant unable to comply with the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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:
Read more
- 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
Read the 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.
- Conditions
- Healthy Women of Child Bearing Potential
- Being tested
- R21/Matrix-M1, Saline and R21/Matrix-M1, Sterile isotonic (0.9%) normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R21/Matrix-M1Biological
10 µg of R21 and 50 µg of Matrix-M1
Saline and R21/Matrix-M1Biological
Also called R21/Matrix-M1
Saline and 10 µg of R21 and 50 µg of Matrix-M1
Sterile isotonic (0.9%) normal salineOther
Also called Placebo
Saline
| Study group | Role | What they receive |
|---|---|---|
| Experimental-Standard Regime Malaria Vaccine Group1 | Active comparator | Participants receiving three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2. Receives: 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 Receives: 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 Receives: Other: Sterile isotonic (0.9%) normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of local and systemic solicited adverse events (AEs)
- Incidence of local and systemic solicited adverse events (AEs) graded by severity.
Measured: Within 7 days after each vaccine administration and over 6 months post third vaccination
Number of participants with P falciparum infection
- falciparum blood stage infection defined as time to first positive blood smear
Measured: Over 6 months post third vaccination
Secondary outcomes (4)
Assessment of safety and tolerabilty
- Occurrence of unsolicited adverse events 28 days follow-up following the vaccination.
- Occurrence of serious adverse events for the whole study duration including in women who become pregnant.
Measured: Through study completion, an average of 26 months
Anti-CSP antibody concentrations
Immunological assessment measuring the anti-CSP antibody concentrations in healthy Malian women of child bearing potential
Measured: Through study completion. Timepoints: baseline, days 70, 84, 140, 196, 434, 448, 504 and 560
Rate of P.falciparum infection during pregnancy
- falciparum blood stage infection defined as time to first positive blood smear during pregnancy
Measured: Over 9-months pregnancy
Rate of P.falciparum infection
- falciparum blood stage infection defined as time to first positive blood smear.
Measured: Over 12-, 18- and 24-months post third vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start19 Mar 2025
- Primary completion1 Sep 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Healthy Women of Child Bearing PotentialStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Malaria Research and Training Center, Bamako, Mali, European Vaccine Initiative
- Responsible party
- Sponsor
- Investigators
- Adrian Hill, MD, Study director, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06080243
- Sponsor's protocol ID
- VAC 094
- Status last verified
- Feb 2026
- First submitted
- 28 Aug 2023
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33964223Datoo 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.
PubMed 36087586