A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 Combined With R21/Matrix-M (a "Multi-stage" Malaria Vaccine)

NCT06958198 | Recruiting Phase 1 DMC

• 1 other identifier: VAC093
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib age de-escalation, dose escalation, open-label study to assess the safety and immunogenicity of the multi-stage malaria vaccine candidate R21 plus RH5.1 and/or R78C in Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (1)

• Safety: To assess the safety and reactogenicity of R21, RH5.1 and R78C in Matrix-M™ when used in different combinations in healthy adults and children living in a malaria-endemic area.

  The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed: * Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination (day of vaccination and 6 subsequent days) * Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination (day of vaccination and 6 subsequent days) * Occurrence of unsolicited adverse events for 28 days following the vaccination (day of vaccination and 27 subsequent days) * Clinically significant change from baseline for safety laboratory measures throughout the study * Occurrence of serious adverse events during the whole study duration.

  Solicited AEs will be assessed at Day 0, Days 1-6, 28, days 29-34, 182 and days 187. Unsolicited AEs on Day 0, Days 1-6, 14, 28, Days 29-34, 42, 56, 182, Days 183-187 and 196. All SAEs will be assessed throughout the study follow up period upto Day 365

Secondary Outcomes (1)

• Immunogenicity: To assess the humoral immunogenicity of R21, RH5.1 and R78C in Matrix-M™ when used in different combinations in healthy adults and children living in a malaria-endemic area.

  Immunology blood samples will be collected at screening, day of vaccination, at Days 42, 56, 182, 196, 210, 240, and 365.

Study Arms (6)

Group 1(n=8) adults (18-35years)

EXPERIMENTAL

They will receive three doses of 5 µg R21 + 10 µg RH5.1 + 10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: R21; Biological: RH5.1; Biological: R78C; Biological: Matrix-M™

Group 2 (n=8) Children aged between 5-17months

EXPERIMENTAL

They will receive three doses of 5 µg R21 + 10 µg RH5.1, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: R21; Biological: RH5.1; Biological: Matrix-M™

Group 3 (n=8) children aged between 5-17 months

EXPERIMENTAL

They will receive three doses of 5 µg R21 + 10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: R21; Biological: R78C; Biological: Matrix-M™

Group 4 (n=8) Children aged between 5-17 months

EXPERIMENTAL

They will receive three doses of 5 µg R21 + 10 µg RH5.1 +10 µg R78C , administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: R21; Biological: RH5.1; Biological: R78C; Biological: Matrix-M™

Group 5 (n=8) children aged 5-17 months

EXPERIMENTAL

They will receive three doses of 5 µg R21, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: R21; Biological: Matrix-M™

Group 6 ( n=16) Children 5-17 months

EXPERIMENTAL

They will receive three doses of 10 µg RH5.1 +10 µg R78C, administered at Month 0 (Day 0), Month 1 (Day 28), and Month 6 (Day 182), given as an Intramuscular injection to the deltoid region (adults) or anterolateral thigh (children)

Biological: RH5.1; Biological: R78C; Biological: Matrix-M™

Interventions

R21 BIOLOGICAL

A protein particle comprising recombinant HBsAg fused to the central repeat and the C-terminus of the circumsporozoite protein

Group 1(n=8) adults (18-35years); Group 2 (n=8) Children aged between 5-17months; Group 3 (n=8) children aged between 5-17 months; Group 4 (n=8) Children aged between 5-17 months; Group 5 (n=8) children aged 5-17 months

RH5.1 BIOLOGICAL

A soluble protein vaccine against the RH5 antigen

Group 1(n=8) adults (18-35years); Group 2 (n=8) Children aged between 5-17months; Group 4 (n=8) Children aged between 5-17 months; Group 6 ( n=16) Children 5-17 months

R78C BIOLOGICAL

A soluble RIPR EGF-CyRPA fusion protein vaccine

Group 1(n=8) adults (18-35years); Group 3 (n=8) children aged between 5-17 months; Group 4 (n=8) Children aged between 5-17 months; Group 6 ( n=16) Children 5-17 months

Matrix-M™ BIOLOGICAL

A saponin-based vaccine adjuvant

Group 1(n=8) adults (18-35years); Group 2 (n=8) Children aged between 5-17months; Group 3 (n=8) children aged between 5-17 months; Group 4 (n=8) Children aged between 5-17 months; Group 5 (n=8) children aged 5-17 months; Group 6 ( n=16) Children 5-17 months

Eligibility Criteria

• Age: 5 Months - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Group 1: Healthy adult aged 18-35 years at the time of first study vaccination
• Group 2-6: Healthy child aged 5-17 months at the time of first study vaccination
• Group 1: Female participants must be non-pregnant (as demonstrated by a negative urine pregnancy .
• test), and practice continuous effective contraception until three months after the final study vaccination
• Participant or parent/guardian provides signed/thumb-printed informed consent
• Participant (and parent/guardian for child participants) resident in the study area villages, and anticipated to be available for vaccination and the duration of follow-up -

You may not qualify if:

• The participant may not enter the trial if ANY of the following apply:
• Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
• Clinically significant skin disorder (psoriasis, contact dermatitis, etc.), cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as judged by the PI or other delegated individual.
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• Children with 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.
• Sickle cell disease.
• Clinically significant laboratory abnormality at grade 2 or above as judged by the PI or other delegated individual.
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• Receipt of any vaccine in the 14 days preceding enrolment, or planned receipt of any other vaccine within 28 days following each study vaccination.
• History of vaccination with any malaria vaccine.
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
• Suspected or known current alcohol misuse.
• Suspected or known injecting drug use in the 5 years preceding enrolment.

Sponsors & Collaborators

• Institut de Recherche en Sciences de la Sante, Burkina Faso: collaborator
• University of Oxford: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Wellcome Trust: collaborator
• European Vaccine Initiative: collaborator
• Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR): collaborator

Study Sites (1)

Institut de Recherche en Sciences de la Santé

Siglé, Boulkiemdé Province, BP 7192 OUAGADOUGOU 03, BF, Burkina Faso

RECRUITING

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

R21 monoclonal antibody; Matrix-M

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Naomi N Kamau

CONTACT

+44 (0)1865611418; vaccinetrials@ndm.ox.ac.uk

Angela Minassian, Honorary Consultant and CI

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase Ib age de-escalation, dose escalation, open label study to assess the safety and immunogenicity of the multi-stage malaria vaccine candidate R21 plus RH5.1 and/or R78C in Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso. 8 healthy adults aged 18-35 years and 48 children aged 5-17 months living in a malaria endemic area will be recruited at one site in Burkina Faso. Adults will be recruited into one group receiving the combination of R21 + RH5.1 + R78C in Matrix-M. Children will be recruited into four groups receiving the combination of the three vaccines, R21 + RH5.1/Matrix-M, R21 + R78C/Matrix-M, R21/Matrix-M only or RH5.1 + R78C/Matrix-M only. Follow-up will be for 6 months post third vaccination.

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 6, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 11, 2026

Record last verified: 2025-04

Locations

BU (1)