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
Overview
- Phase
- Phase 1
- Intervention
- R21/Matrix M™ (Group 1)
- Conditions
- Malaria,Falciparum
- Sponsor
- University of Oxford
- Enrollment
- 36
- Locations
- 4
- Primary Endpoint
- 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
- Status
- Active, Not Recruiting
- Last Updated
- 19 days ago
Overview
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.
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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
Intervention: R21/Matrix M™ (Group 1)
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
Intervention: Fine needle aspiration (FNA)
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 (subgroup 2A)/280 (subgroup 2B) via intramuscular (IM) injection in the deltoid region of the same arm
Intervention: R21/Matrix M™ (Group 2)
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 (subgroup 2A)/280 (subgroup 2B) via intramuscular (IM) injection in the deltoid region of the same arm
Intervention: Fine needle aspiration (FNA)
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
Intervention: R21/Matrix M™ (Group 3)
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
Intervention: Fine needle aspiration (FNA)
Outcomes
Primary Outcomes
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
Time Frame: 7 days post-vaccination
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.
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
Time Frame: 28 days post-vaccination.
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.
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
Time Frame: For the follow-up period of the study, between 1-2 years
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.
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
Time Frame: For the follow-up period of the study, between 1-2 years
Antibody dynamics will be assessed by measuring NANP-IgG at baseline and various timepoints during the trial.