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

NCT ID: NCT05357560

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-10
• Study Completion Date: 2025-06-30

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

Detailed Description

A total of 96 volunteers will be enrolled. Adults (18-45 years) will be enrolled into groups 3 -5. Infants (5 -17 months) will be enrolled into groups 1-2 and groups 6-9. All volunteers will be given 3 doses 50 µg of Matrix-M in combination with RH5.2 VLP and/or R21 via intramuscular (IM) injection in the deltoid region of the non-dominant arm for adults and anterolateral thigh for infants. The first 2 doses will be given at months 0 and 1. Groups 2-6 and group 8 will be given the third dose at month 2, and groups 1, 7 and 9 will be given the third dose at month 6.

Conditions

Malaria, Plasmodium Falciparum

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Group 1 - Infants R21 delayed 3rd dose

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 2 - Infants R21 standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 3 - Adults RH5.2 low dose, standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 4 - Adults RH5.2 high dose, standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 5 - Adults RH5.2 and R21 low dose, standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 6 - Infants RH5.2 standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 7 - Infants RH5.2, delayed 3rd dose

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 8 - Infants RH5.2 and R21, standard regimen

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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 9 - Infants RH5.2 and R21, delayed 3rd dose

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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

Interventions

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

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Positive malaria by PCR screening.
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Any other 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.

The following events associated with vaccine immunisation constitute absolute contraindications to further administration of vaccine. If any of these events occur during the study, the participant must be withdrawn and followed until resolution of the event, as with any adverse event:

• Anaphylactic reaction following administration of vaccine.
• Pregnancy. The following adverse events constitute contraindications to administration of vaccine at that point in time; if any one of these adverse events occurs at the time scheduled for vaccination, the participant may be vaccinated at a later date, or withdrawn at the discretion of the Investigator.

The participant must be followed until resolution of the event as with any adverse event:

• Acute disease at the time of administration of the IP (acute disease is defined as the presence of a moderate or severe illness with or without fever or symptoms suggestive of possible COVID-19 disease). All vaccines can be administered to persons with a minor illness such as diarrhoea or mild upper respiratory infection without fever, i.e. axillary temperature < 37.5°C.
• Temperature of >37.5°C (99.5°F) at the time of vaccination.
• Confirmed current COVID-19 infection, defined as ongoing symptoms with positive COVID-19 PCR swab or rapid antigen test taken during current illness or positive COVID-19 PCR swab or rapid antigen test within preceding 7 days without symptoms. Vaccinations will be delayed by a minimum of 7 days from the date of the first positive COVID-19 PCR swab, as long as symptoms are improving or resolved and there is no fever. It will be at the discretion of the Investigator to withdraw a participant if they develop severe COVID-19 disease.

• Minimum Eligible Age: 5 Months
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

European and Developing Countries Clinical Trials Partnership (EDCTP)

OTHER_GOV

Sponsor Role: collaborator

Medical Research Council Unit, The Gambia

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Umberto D'Alessandro

Role: PRINCIPAL_INVESTIGATOR

Medical Research Council Unit, The Gambia

Locations

Medical Research Council Unit, Fajara

Banjul, , The Gambia

Countries

The Gambia

References

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.

Reference Type: DERIVED

PMID: 40245769 (View on PubMed)

Other Identifiers

VAC086

Identifier Type: -

Identifier Source: org_study_id