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

A Phase 1 Study to Assess the Safety and Immunogenicity of R21/Matrix-M™ Administered in an Escalating Dose, Multi-prime Vaccination Schedule in Healthy Adults

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.

Study Overview

• Status: Recruiting
• Conditions: Malaria,Falciparum
• Intervention / Treatment: Biological: R21/Matrix M™ (Group 1); Procedure: Fine needle aspiration (FNA); Biological: R21/Matrix M™ (Group 2); Biological: R21/Matrix M™ (Group 3)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Volunteer Co-ordinators; Phone Number: 01865611386; Email: vaccinetrials@ndm.ox.ac.uk

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS2 8HW
    • Not yet recruiting
    • University Hospitals Bristol and Weston NHS Foundation Trust
    • Contact: Rajeka Lazarus, DPhil FCRPath; Email: rajeka.lazarus@uhbristol.nhs.uk
    • Principal Investigator: Rajeka Lazarus, DPhil FRCPath
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Recruiting
      • Centre for Clinical Vaccinology and Tropical Meducine, Churchill Hospital, University of Oxford
      • Contact: Volunteer Recruitment Co-ordinator; Phone Number: 01865611386; Email: vaccinetrials@ndm.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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); Procedure: 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.
Experimental: 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	Procedure: 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.; 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)
Experimental: 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	Procedure: 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.; Biological: R21/Matrix M™ (Group 3); 10 mcg R21 in 50 mcg Matrix-M™ (D0); 10 mcg R21 in 50 mcg Matrix-M™ (D56)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the safety of R21/Matrix-M™ administered in an escalating dose, multi prime vaccination schedule with a standard prime-boost regimen in healthy UK adults	Occurrence of solicited (local and systemic reactogenicity) adverse events, unsolicited adverse events, and changes from baseline in laboratory parameters for 7 days following vaccination. Solicited and 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.	7 days post-vaccination
To compare the safety of R21/Matrix-M™ administered in an escalating dose, multi prime vaccination schedule with a standard prime-boost regimen in healthy UK adults	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
To compare the humoral immunogenicity of R21/Matrix-M™ administered in an escalating dose, multi-prime vaccination schedule with 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the relationship between vaccination schedule and humoral immune response in participants vaccinated with R21/Matrix-M™ administered in escalating dose, multi-prime vaccination schedules compared with a standard prime-boost regimen	(Exploratory outcome measure) Exploratory immunology to further investigate the relationship between cellular and humoral immunity and vaccine regimen.	For the follow-up period of the study, between 1-2 years

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Bill and Melinda Gates Foundation; University Hospitals Bristol and Weston NHS Foundation Trust
• Investigators: Principal Investigator: 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

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Mosquito-Borne Diseases; Malaria, Falciparum
• Other Study ID Numbers: VAC096

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No