Safety, Immunogenicity and Efficacy of R21 Matrix-M in 5-17 Month Old Children in Nanoro, Burkina Faso

NCT03896724 | Completed Phase 1 DMC

• 1 other identifier: VAC076
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double blind randomised controlled clinical trial to evaluate the efficacy of R21 adjuvanted with Matrix-M in healthy 5-17 month old children in a malaria endemic area.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (1)

• The protective efficacy (number of cases) against clinical malaria of R21 adjuvanted with Matrix-M in 5-17 month old children living in a malaria-endemic area

  We will look for the presence of axillary temperature ≥37.5°C AND P. falciparum parasites density \> 5000 asexual forms/µL as a primary case definition of clinical malaria. \- We will look for the presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum parasites density \> 0 for a secondary case definition of clinical malaria.

  for 6 months after the last vaccination

Secondary Outcomes (4)

• Duration of Protective efficacy (number of cases) against clinical malaria

  for 12 months after administration of the third dose of vaccine, and for 6 and 12 months after each booster vaccination

• Efficacy (number of cases) against asymptomatic P. falciparum infection

  at 6 and 12 months after administration of the third dose of vaccine, and for 12 months after each booster vaccination

• The safety and reactogenicity (number of adverse events) of R21 adjuvanted with Matrix-M in 5-17 month olds living in a malaria-endemic area in the month following each vaccination and at 12 months after administration of the final dose of vaccine

  for 6 and 12 months after administration of the third dose of vaccine, and for 12 months after each booster vaccination

• The humoral immunogenicity (antibody response) of R21 adjuvanted with Matrix-M in 5-17 months old children living in a malaria-endemic area

  for 6 and 12 months after administration of the third dose of vaccine, and for 6 months after each booster vaccination

Other Outcomes (3)

• Exploratory Objectives: Efficacy (number of cases) against incident cases of severe malaria

  12 months after administration of the final dose of vaccine

• Exploratory Objectives: Gut microbiome (bacterial communities identified) effect on vaccine response.

  for 12 months after administration of the final dose of vaccine

• Exploratory Objectives: Genetic testing to elicit differences in vaccine response.

  for 12 months after administration of the final dose of vaccine

Study Arms (3)

Group 1

EXPERIMENTAL

n=150. Age 5-17 month-old. 5mcg R21/25mcg Matrix-M at Day 0, 28 and 56 and 1 year. Following the initial booster, Group 1 will be randomised 2:1 into Groups1a and 1b for 5ug R21/50ug Matrix-M: control. Groups 1a and 1b will receive these second and third booster vaccinations each year prior to the malaria season

Biological: R21 adjuvanted with 25mcg Matrix-M; Biological: Rabies Vaccine; Biological: R21 adjuvanted with 50mcg Matrix-M

Group 2

EXPERIMENTAL

n=150. Age 5-17 month-old. 5mcg R21/50mcg Matrix-M at Day 0, 28 and 56 and 1 year. Following the initial booster, Group 2 will be randomised 2:1 into Groups 2a and 2b or 5ug R21/50ug Matrix-M:ccontrol. Groups 2a and 2b will receive these second and third booster vaccinations each year prior to the malaria season

Biological: Rabies Vaccine; Biological: R21 adjuvanted with 50mcg Matrix-M

Group 3 (control group)

PLACEBO COMPARATOR

n=150. Age 5-17 month-old. Rabies Vaccine by the end of the trial.

Biological: Rabies Vaccine

Interventions

R21 adjuvanted with 25mcg Matrix-M BIOLOGICAL

Vaccine

Group 1

Rabies Vaccine BIOLOGICAL

Vaccine

Group 1; Group 2; Group 3 (control group)

R21 adjuvanted with 50mcg Matrix-M BIOLOGICAL

vaccine

Group 1; Group 2

Eligibility Criteria

• Age: 5 Months - 17 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy child aged 5-17 months at the time of first study vaccination
• Provide written Informed consent of parent/guardian
• Child and parent/guardian resident in the study area villages and anticipated to be available for vaccination and follow-up for 2 years following last dose of vaccination

You may not qualify if:

• Clinically significant skin disorder (psoriasis, contact dermatitis etc.), immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness.
• Weight-for-age Z score of less than -3 or other clinical signs of malnutrition.
• History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. neomycin.
• Sickle cell disease.
• Clinically significant laboratory abnormality as judged by the study clinician.
• Blood transfusion within one month of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• Previous vaccination with experimental malaria vaccines.
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Current participation in another clinical trial, or within 12 weeks of this study.
• Known maternal HIV infection (No testing will be done by the study team).
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (For corticosteroids, this will mean prednisone, or equivalent, \>= 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
• Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.

Sponsors & Collaborators

• University of Oxford: lead
• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Institut de Recherche en Sciences de la Sante - Clinical Research Unit of Nanoro (IRSS-URCN)

Nanoro, Burkina Faso

Location

Related Publications (3)

• Mukhopadhyay ES, Bellamy DG, Tinto H, Hamaluba M, Truby A, Salman AM, Hill AVS. Naturally acquired immune responses to alpha-gal in malaria endemic settings and pre-clinical efficacy testing with R21/MM. Vaccine. 2025 Dec 5;68:127897. doi: 10.1016/j.vaccine.2025.127897. Epub 2025 Nov 1.

  PMID: 41176969 DERIVED

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Matrix-M; Rabies Vaccines

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: April 1, 2019
• Study Start: May 7, 2019
• Primary Completion: July 7, 2023
• Study Completion: July 7, 2023
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 12 months of manuscripts related to the trial being published.
• Access Criteria: A link to the data respository will be given below

Locations

BU (1)