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

NCT ID: NCT06320535

Last Updated: 2025-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-25

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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This is a study to assess safety and immunogenicity of a novel dosing regimen for R21/ Matrix-M™, a leading Plasmodium falciparum malaria vaccine, in healthy, malaria-naïve adults. Participants in the study will receive either 6 escalating doses (groups 1 and 2) or 2 standard doses (group 3) of R21/ Matrix-M™, all delivered in the same arm. Up to 36 volunteers will be enrolled and followed up for 12-24 months after their first vaccine.

In addition to blood sampling throughout the follow-up period, participants will undergo fine needle aspiration of axillary lymph nodes twice during the study, to allow further characterisation of immune responses to this novel vaccine regimen.

Conditions

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Malaria,Falciparum

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Group 1: Escalating dose R21/Matrix M™

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

Group Type EXPERIMENTAL

R21/Matrix M™ (Group 1)

Intervention Type 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)

Fine needle aspiration (FNA)

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

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

Group Type EXPERIMENTAL

R21/Matrix M™ (Group 2)

Intervention Type 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™(D168)

Fine needle aspiration (FNA)

Intervention Type 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 3: Standard dose R21/Matrix-M™

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

Group Type EXPERIMENTAL

R21/Matrix M™ (Group 3)

Intervention Type BIOLOGICAL

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

Fine needle aspiration (FNA)

Intervention Type 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.

Interventions

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R21/Matrix M™ (Group 1)

* 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)

Intervention Type BIOLOGICAL

R21/Matrix M™ (Group 2)

* 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)

Intervention Type BIOLOGICAL

R21/Matrix M™ (Group 3)

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

Intervention Type BIOLOGICAL

Fine needle aspiration (FNA)

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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
* Participants unable to be closely followed for social, geographic or psychological reasons.
* Investigator inability to corroborate a participant's medical history via access to NHS electronic records and/or their GP.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Bill and Melinda Gates Foundation

OTHER

Sponsor Role collaborator

University Hospitals Bristol and Weston NHS Foundation Trust

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanne Hodgson, DPhil FRCP

Role: PRINCIPAL_INVESTIGATOR

Center for Clinical Vaccinology and Tropical Medicine, University of Oxford

Rajeka Lazarus, DPhil FRCP

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Bristol and Weston Foundation Trust

Locations

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

Oxford, Oxfordshire, United Kingdom

Site Status

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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VAC096

Identifier Type: -

Identifier Source: org_study_id

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