A Study to Assess the Experimental Malaria Vaccines RH5.2-VLP and R21

NCT05357560 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: VAC086
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib multi-stage Plasmodium falciparum malaria vaccine study to assess the safety and immunogenicity of the blood-stage vaccine candidate RH5.2 virus-like particle (VLP) in Matrix-MTM and the pre-erythrocytic stage vaccine candidate R21 in Matrix-MTM, both alone and in combination, in adults and infants in the Gambia

Conditions

Malaria, Plasmodium Falciparum

Keywords

RH5.2 virus-like particle (VLP); Matrix-M; R21

Outcome Measures

Primary Outcomes (5)

• To determine safety and tolerability of RH5.2-VLP with Matrix-M and R21 with Matrix-M, in healthy adults and infants by assessing the occurrence of solicited local reactogenicity signs and symptoms via clinic and home visits

  Occurrence of solicited local reactogenicity signs and symptoms via clinic and home visits

  7 days following each vaccination

• To determine safety and tolerability of RH5.2-VLP with Matrix-M and R21 with Matrix-M, in healthy adults and infants by assessing the occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits

  Occurrence of solicited systemic reactogenicity signs and symptoms via clinic and home visits

  7 days following each vaccination

• To determine safety and tolerability of RH5.2-VLP with Matrix-M and R21 with Matrix-M, in healthy adults and infants by assessing occurrence of unsolicited adverse events

  Occurrence of unsolicited adverse events via clinical review, clinical examination (including observations) and laboratory results

  28 days following the vaccination

• Safety of the RH5.2-VLP with Matrix-M and R21 with Matrix-M vaccine, assessed through the number of participants with abnormal laboratory test results

  Occurrence of change from baseline laboratory test results

  28 days following the vaccination

• Assessment of safety and tolerability of RH5.2-VLP with Matrix-M and R21 with Matrix-M, in healthy adults and infants assessed through the number of participants with serious adverse events

  Occurrence of serious adverse events including grading of causality

  Whole duration of the study (24-30 months following initial trial vaccination)

Secondary Outcomes (14)

• To assess the humoral and cellular immunogenicity of RH5.2-VLP with Matrix-M as assessed by magnitude assessment at various timepoint

  From a number of key timepoints, baseline up to day 912 (dependant on group)

• To assess the humoral and cellular immunogenicity of RH5.2-VLP with Matrix-M as assessed by antibody kinetics at various timepoints

  From a number of key timepoints, baseline up to day 912 (dependant on group)

• To assess the humoral and cellular immunogenicity of RH5.2-VLP with Matrix-M, performing ELISA at various timepoints

  From a number of key timepoints, baseline up to day 912 (dependant on group)

• To assess the humoral and cellular immunogenicity of R21 with Matrix-M performing ELISA at various timepoints

  From a number of key timepoints, baseline up to day 912 (dependant on group)

• To assess the humoral and cellular immunogenicity of R21 with Matrix-M as assessed by antibody kinetics at various timepoints

  From a number of key timepoints, baseline up to day 912 (dependant on group)

Study Arms (9)

Group 1 - Infants R21 delayed 3rd dose

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50 µg of Matrix-M in combination with 5µg R21 at months 0, 1 and 6 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 2 - Infants R21 standard regimen

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50 µg of Matrix-M in combination with 5µg R21 at months 0, 1 and 2 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 3 - Adults RH5.2 low dose, standard regimen

EXPERIMENTAL

10 volunteers (adult 18-45 years) given 50 µg of Matrix-M in combination with 10µg RH5.2 VLP at months 0, 1 and 2 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 4 - Adults RH5.2 high dose, standard regimen

EXPERIMENTAL

10 volunteers (adult 18-45 years) given 50 µg of Matrix-M in combination with 50µg RH5.2 VLP at months 0, 1 and 2 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 5 - Adults RH5.2 and R21 low dose, standard regimen

EXPERIMENTAL

10 volunteers (adult 18-45 years) given 50 µg of Matrix-M in combination with 10µg RH5.2 VLP and 10µg R21 at months 0, 1 and 2 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 6 - Infants RH5.2 standard regimen

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50µg of Matrix-M in combination with 5µg RH5.2 VLP at months 0, 1 and 2 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 7 - Infants RH5.2, delayed 3rd dose

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50µg of Matrix-M in combination with 5µg RH5.2 VLP at months 0, 1 and 6 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 8 - Infants RH5.2 and R21, standard regimen

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50µg of Matrix-M in combination with 5µg RH5.2 VLP and 5µg R21 at months 0, 1 and 2 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Group 9 - Infants RH5.2 and R21, delayed 3rd dose

EXPERIMENTAL

11 volunteers (infant 5-17 months) given 50µg of Matrix-M in combination with 5µg RH5.2 VLP and 5µg R21 at months 0, 1 and 6 via intramuscular (IM) injection in the anterolateral thigh

Biological: Matrix-M with RH5.2 VLP and/or R21

Interventions

Matrix-M with RH5.2 VLP and/or R21 BIOLOGICAL

3 doses of 50 µg of Matrix-M in combination with RH5.2 VLP and/or R21 at different doses and at different timepoints

Group 1 - Infants R21 delayed 3rd dose; Group 2 - Infants R21 standard regimen; Group 3 - Adults RH5.2 low dose, standard regimen; Group 4 - Adults RH5.2 high dose, standard regimen; Group 5 - Adults RH5.2 and R21 low dose, standard regimen; Group 6 - Infants RH5.2 standard regimen; Group 7 - Infants RH5.2, delayed 3rd dose; Group 8 - Infants RH5.2 and R21, standard regimen; Group 9 - Infants RH5.2 and R21, delayed 3rd dose

Eligibility Criteria

• Age: 5 Months - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Groups 1, 2 and 6-9: Healthy male or female infants aged 5-17 months at the time of enrolment with signed consent obtained from parents or guardians.
• Groups 3-5: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
• Groups 3-5 (Female participants only): Must be non-pregnant (as demonstrated by a negative urine pregnancy test), and practice continuous effective contraception for the 24 to 30 month duration of the study (see section 9.9).
• Planned long-term (at least 24 months from the date of recruitment) or permanent residence in the study area.
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or infants with Z-score of weight-for-age within ±2SD.

You may not qualify if:

• Clinically significant congenital abnormalities as judged by the PI or other delegated individual
• Clinically significant history of skin disorder (psoriasis, contact dermatitis etc.), allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness as judged by the PI or other delegated individual.
• 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 (inhaled and topical steroids are allowed).
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, betapropiolactone.
• Any history of anaphylaxis in relation to vaccination.
• 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 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination. This excludes COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination, and EPI vaccines (for infants), which should not be received between 14 days before to 28 days after any study vaccination.
• History of vaccination with previous malaria vaccines
• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment in adults or at any time for infants, or planned use during the study period.
• Suspected or known current alcohol abuse.
• Suspected or known injecting drug abuse in the 5 years preceding enrolment.
• Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C (HCV IgG) or HIV. For infants, any history of vertical exposure to HIV infection.
• Any other finding which in the opinion of the PI or other delegated individual would increase the risk of an adverse outcome from participation in the trial.

Sponsors & Collaborators

• University of Oxford: lead
• Medical Research Council Unit, The Gambia: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Medical Research Council Unit, Fajara

Banjul, PO Box 273, The Gambia

Location

Related Publications (1)

• Mo AX, McGugan G, Pesce JT. Meeting report: Expert consultation on late arresting replication competent (LARC) malaria sporozoite vaccine research & development. Vaccine. 2025 Apr 30;54:127009. doi: 10.1016/j.vaccine.2025.127009. Epub 2025 Apr 16.

  PMID: 40245769 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Matrix-M

Condition Hierarchy (Ancestors)

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

Study Officials

• Umberto D'Alessandro

  Medical Research Council Unit, The Gambia

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 13, 2022
• First Posted: May 3, 2022
• Study Start: July 10, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 11, 2026

Record last verified: 2025-03

Locations

TH (1)