A Phase Ia Clinical Trial to Assess the Safety and Immunogenicity of the Blood-stage Malaria Candidate Vaccines RH5.1 in Matrix-M and R78C in Matrix-M in Healthy UK Adults

NCT05385471 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: VAC089
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-centre Phase I P. falciparum blood-stage vaccine trial to assess the safety and immunogenicity and efficacy of the candidate malaria vaccines R78C and RH5.1 formulated in adjuvant Matrix-M

Conditions

Malaria, Falciparum

Keywords

R78C; RH5.1; Matrix-M

Outcome Measures

Primary Outcomes (5)

• To assess the safety of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy adult volunteers at alone and in combination by assessing the occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination

  Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination. These will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales.

  7 days following each vaccination

• To assess the safety of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy adult volunteers at alone and in combination by assessing the occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination

  Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination. These will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales.

  7 days following each vaccination

• To assess the safety of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy adult volunteers at alone and in combination by assessing the occurrence of unsolicited adverse events for 28 days following the vaccination

  Occurrence of unsolicited adverse events for 28 days following the vaccination. These will be tabulated, detailing frequency, duration and severity of AEs. Haematological and biochemical laboratory values will be presented according to local grading scales.

  28 days following the vaccination

• To assess the safety of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy adult volunteers at alone and in combination, assessed through the number of participants with abnormal laboratory test results

  Occurrence of change from baseline laboratory tests

  28 days following vaccination

• To assess the safety of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy adult volunteers at alone and in combination, assessed through the number of participants with serious adverse events

  Occurrence of serious adverse events during the whole study duration. Haematological and biochemical laboratory values will be presented according to local grading scales.

  Whole duration of the Study (up to day 600 depending on group)

Secondary Outcomes (5)

• To assess the humoral immunogenicity of R78C in Matrix-M™ and RH5.1 in Matrix-M when administered to healthy volunteers alone and in combination assessing antigen-specific IgG antibody levels, with comparison before and after vaccination

  From a number of key timepoints, baseline up to day 600 (dependant on group)

• To assess the humoral immunogenicity of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy volunteers assessing antigen-specific antibody subclass/isotype measurement, with comparison before and after vaccination

  From a number of key timepoints, baseline up to day 600 (dependant on group)

• To assess the humoral immunogenicity of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy volunteers assessing antigen-specific antibody avidity measurement, with comparison before and after vaccination

  From a number of key timepoints, baseline up to day 600 (dependant on group)

• To assess the humoral immunogenicity of R78C in Matrix-M™ and RH5.1 in Matrix-M when administered to healthy volunteers alone and in combination assessing In vitro GIA, with comparison before and after vaccination

  From a number of key timepoints, baseline up to day 600 (dependant on group)

• To assess the humoral immunogenicity of R78C in Matrix-M™ and RH5.1 in Matrix-M in healthy volunteers assessing Purified IgG ELISA versus GIA titration "Quality Analysis", with comparison before and after vaccination

  From a number of key timepoints, baseline up to day 600 (dependant on group)

Study Arms (4)

Group 1

EXPERIMENTAL

8+1 volunteers receiving three doses of 10 µg R78C with 50 µg of Matrix-M on days 0, 28 and 182 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix M with R78C and/or RH5.1

Group 2

EXPERIMENTAL

8+1 volunteers receiving three doses of 10 µg R78C + 10 µg RH5.1 with 50 µg of Matrix-M on days 0, 28 and 182 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix M with R78C and/or RH5.1

Group 3

EXPERIMENTAL

8+1 volunteers receiving three doses of 10 µg RH5.1 with 50 µg of Matrix-M on days 0, 28 and 56 via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix M with R78C and/or RH5.1

Group 4

EXPERIMENTAL

8+1 volunteers receiving two doses of 10 µg R78C + 10 µg RH5.1 with 50 µg of Matrix-M on days 0, 28, one dose of 10 µg R78C with 50 µg of Matrix-M on day 182 and one dose of 10 µg RH5.1 with 50 µg of Matrix-M on day 210, all administered via intramuscular (IM) injection in the deltoid region of the non-dominant arm

Biological: Matrix M with R78C and/or RH5.1

Interventions

Matrix M with R78C and/or RH5.1 BIOLOGICAL

50 µg of Matrix-M adjuvant with R78C and/or RH5.1 at different doses and timepoints

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The volunteer must satisfy all the following criteria to be eligible for the study:
• Healthy adult aged 18 to 45 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow the Investigators to discuss the volunteer's medical history with their GP
• Participants of childbearing potential only: must practice continuous effective contraception until 3 months after the final study vaccination (see section 9.10)
• Agreement to refrain from blood donation for the duration of the study
• Able and willing to provide written informed consent to participate in the trial

You may not qualify if:

• The volunteer may not enter the study if any of the following apply:
• History of clinical malaria (any species) or previous participation in any malaria vaccine trial or controlled human malaria infection trial
• Travel to a clearly malaria endemic locality during the study period or within the preceding six months
• Use of immunoglobulins or blood products (e.g. blood transfusion) in the last three months
• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
• Concurrent involvement in another clinical trial involving an investigational product or planned involvement during the study period
• Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator
• 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 allergic disease or reactions likely to be exacerbated by any component of the vaccine
• Any history of anaphylaxis in reaction to vaccinations
• Pregnancy, lactation or intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition that may affect participation in the study
• Any other serious chronic illness requiring hospital specialist supervision

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

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

• Angela M Minassian, DPhil FRCP

  Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, United

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 23, 2022
• Study Start: January 13, 2023
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: April 1, 2025

Record last verified: 2025-03

Locations

GB (1)