A Phase 1 Study to Assess an Escalating Dose, Multi-prime Vaccination Schedule of R21/Matrix-M™

NCT06320535 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: VAC096
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase I clinical study that aims to assess the safety and immunogenicity of a novel, escalating dose regimen of R21/Matrix-M™ in healthy, malaria-naïve adults.

Conditions

Malaria,Falciparum

Outcome Measures

Primary Outcomes (4)

• Safety of R21/Matrix-M™ administered in an escalating dose, multi prime vaccination schedule versus a standard prime-boost regimen in healthy UK adults, measured by the number of solicited adverse events in each group

  Occurrence of solicited local and systemic reactogenicity signs and symptoms will be collected for 7 days following each vaccination. Solicited adverse event data will be tabulated, detailing frequency, duration and severity of the AEs.

  7 days post-vaccination

• Safety of R21/Matrix-M™ administered in an escalating dose, multi prime vaccination schedule versus a standard prime-boost regimen in healthy UK adults, measured by the number of unsolicited adverse events and laboratory adverse events in each group

  Occurrence of unsolicited adverse events and changes from baseline in laboratory safety measures will be collected for 28 days following each vaccination. Unsolicited AE data will be tabulated, detailing frequency, duration and severity of AEs. Hematological and biochemical laboratory values will be presented according to local grading scales.

  28 days post-vaccination.

• Safety of R21/Matrix-M™ administered in an escalating dose, multi prime vaccination schedule versus a standard prime-boost regimen in healthy UK adults, measured by the number of serious adverse events in each group

  Occurrence of serious adverse events (SAEs), adverse events of special interest (AESIs) and withdrawal due to AE(s)/SAE(s) will be described in detail.

  For the follow-up period of the study, between 1-2 years

• Humoral immunogenicity of R21/Matrix-M™ administered in an escalating dose, multi-prime vaccination schedule verus a standard prime-boost regimen in healthy UK adults

  Antibody dynamics will be assessed by measuring NANP-IgG at baseline and various timepoints during the trial.

  For the follow-up period of the study, between 1-2 years

Other Outcomes (1)

• Impact of vaccination schedule on immune response in participants vaccinated with R21/Matrix-M™ administered in escalating dose, multi-prime vaccination schedules versus a standard prime-boost regimen

  For the follow-up period of the study, between 1-2 years

Study Arms (3)

Group 1: Escalating dose R21/Matrix M™

EXPERIMENTAL

12 volunteers receiving escalating doses of R21/Matrix M™ adjuvant at days 0, 3, 7, 10, 14, and 56 via intramuscular (IM) injection in the deltoid region of the same arm

Biological: R21/Matrix M™ (Group 1); Procedure: Fine needle aspiration (FNA)

Group 2: Escalating dose R21/Matrix M™ with delayed booster

EXPERIMENTAL

12 volunteers receiving escalating doses of R21/Matrix M™ adjuvant at days 0, 3, 7, 10, 14, 168 (subgroup 2A)/280 (subgroup 2B) via intramuscular (IM) injection in the deltoid region of the same arm

Biological: R21/Matrix M™ (Group 2); Procedure: Fine needle aspiration (FNA)

Group 3: Standard dose R21/Matrix-M™

EXPERIMENTAL

12 volunteers receiving two 10mcg doses of R21 in 50mcg of Matrix M™ adjuvant at days 0 and 56 via intramuscular (IM) injection in the deltoid region of the same arm

Biological: R21/Matrix M™ (Group 3); Procedure: Fine needle aspiration (FNA)

Interventions

R21/Matrix M™ (Group 1) BIOLOGICAL

* 0.50 mcg R21 in 2.75 mcg Matrix-M™ (D0) * 0.75 mcg R21 in 3.5 mcg Matrix-M™ (D3) * 1.25 mcg R21 in 6.25 mcg Matrix-M™ (D7) * 2.5 mcg R21 in 12.5 mcg Matrix-M™ (D10) * 5 mcg R21 in 25 mcg Matrix-M™ (D14) * 10 mcg R21 in 50 mcg Matrix-M™ (D56)

Group 1: Escalating dose R21/Matrix M™

R21/Matrix M™ (Group 3) BIOLOGICAL

* 10 mcg R21 in 50 mcg Matrix-M™ (D0) * 10 mcg R21 in 50 mcg Matrix-M™ (D56)

Group 3: Standard dose R21/Matrix-M™

R21/Matrix M™ (Group 2) BIOLOGICAL

Group 2A: * 0.50 mcg R21 in 2.75 mcg Matrix-M™ (D0) * 0.75 mcg R21 in 3.5 mcg Matrix-M™ (D3) * 1.25 mcg R21 in 6.25 mcg Matrix-M™ (D7) * 2.5 mcg R21 in 12.5 mcg Matrix-M™ (D10) * 5 mcg R21 in 25 mcg Matrix-M™ (D14) * 10 mcg R21 in 50 mcg Matrix-M™(D168) Group 2B: * 0.50 mcg R21 in 2.75 mcg Matrix-M™ (D0) * 0.75 mcg R21 in 3.5 mcg Matrix-M™ (D3) * 1.25 mcg R21 in 6.25 mcg Matrix-M™ (D7) * 2.5 mcg R21 in 12.5 mcg Matrix-M™ (D10) * 5 mcg R21 in 25 mcg Matrix-M™ (D14) * 10 mcg R21 in 50 mcg Matrix-M™(D280)

Group 2: Escalating dose R21/Matrix M™ with delayed booster

Fine needle aspiration (FNA) PROCEDURE

Participants in all groups will undergo fine needle aspiration (FNA) of axillary lymph nodes draining vaccination site on Day 77 and Day 105 after initial vaccination.

Group 1: Escalating dose R21/Matrix M™; Group 2: Escalating dose R21/Matrix M™ with delayed booster; Group 3: Standard dose R21/Matrix-M™

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18 to 50 years.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Participants of childbearing potential only: must practice continuous effective contraception until the last study visit.
• 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:

• 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, as per the CDC website: https://www.cdc.gov/malaria/travelers/country\_table/a.html
• Participation in another research study involving receipt of an investigational medicinal product (IMP) in the 30 days preceding enrolment or 5 half-lives of the investigational medicinal product, whichever is longer, or planned participation during the study period.
• Prior receipt of an IMP likely to impact interpretation of the trial data, as assessed by the Investigator.
• Receipt of any vaccine within 30 days of a study vaccine, with the exception of COVID-19 vaccination.
• Receipt of oral or systemic immunosuppressant medication for more than 14 days in the six months preceding enrolment.
• Receipt of immunoglobulins or blood products (e.g. blood transfusion) in the three months preceding enrolment.
• History of anaphylaxis to vaccination, or allergy likely to be exacerbated by any component of the vaccine or study procedures, including allergy to lidocaine
• Pregnancy, lactation or intention to become pregnant during the study.
• Clinically significant history of chronic disease, including cancer (except basal cell carcinoma or cervical carcinoma in situ), immunodeficiency (including HIV), autoimmune conditions (except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease), psychiatric disorder, drug or alcohol abuse
• Positive Hepatitis B surface antigen (HBsAg), HIV antibodies or Hepatitis C (HCV) antibodies (except previous HCV vaccine study participants)
• HEMStop score \> or = to 2(30) with abnormal coagulation screen or clinical concern regarding bleeding risk.
• Use of medications that increase the risk of bleeding, as assessed by the clinician, including: warfarin, oral antithrombin agents (e.g. Apixaban), low molecular weight heparin
• Any clinically significant abnormality of screening examination, blood or urine tests
• Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may put the volunteer at risk, affect the volunteer's ability to participate in the study or impair interpretation of the study data

Sponsors & Collaborators

• University of Oxford: lead
• Bill and Melinda Gates Foundation: collaborator
• University Hospitals Bristol and Weston NHS Foundation Trust: collaborator

Study Sites (2)

Centre for Clinical Vaccinology and Tropical Meducine, Churchill Hospital, University of Oxford

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, BS2 8HW, United Kingdom

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Biopsy, Fine-Needle

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biopsy, Needle; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques

Study Officials

• Susanne Hodgson, DPhil FRCP

  Center for Clinical Vaccinology and Tropical Medicine, University of Oxford

  PRINCIPAL INVESTIGATOR

• Rajeka Lazarus, DPhil FRCP

  University Hospitals Bristol and Weston Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Participants who opt to receive the escalating dose regimen will be randomized to either Group 1 or Group 2. Recruitment to Groups 1 and 2 will be staggered, as these groups assess a novel administration regimen for R21/Matrix-M: * Two participants will be enrolled first, into Group 1 or 2, with a review of safety data collected up to Day 16 by the DSMC. * If reactogenicity is acceptable, the remaining participants may be enrolled into Groups 1 and Group 2. Participants may be recruited to Group 3 at any time. A second DSMC review will take place 16 days after 10 participants have been recruited in Groups 1 and 2 and 5 participants have been recruited in Group 3. Group 2 is divided into subgroups 2A and 2B, who receive their booster vaccinations at 6 months and 9 months post-first vaccination respectively.

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: March 20, 2024
• Study Start: March 25, 2024
• Primary Completion: June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 13, 2026

Record last verified: 2025-06

Locations

GB (2)