Clinical trial NCT06320535: A Phase 1 Study to Assess an Escalating Dose, Multi-prime Vaccination Schedule of R21/Matrix-M™
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malaria,Falciparum
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: University Hospitals Bristol and Weston NHS Foundation Trust
First posted: 2024-03-20
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: PREVENTION

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.

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
* 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.

Primary outcomes:
measure: 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
timeFrame: 7 days post-vaccination
measure: 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
timeFrame: 28 days post-vaccination.
measure: 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
timeFrame: For the follow-up period of the study, between 1-2 years
measure: 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
timeFrame: For the follow-up period of the study, between 1-2 years
Secondary outcomes:
Other outcomes:
measure: 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
timeFrame: For the follow-up period of the study, between 1-2 years
Locations:
city: Oxford
country: United Kingdom
facility: Centre for Clinical Vaccinology and Tropical Meducine, Churchill Hospital, University of Oxford
state: Oxfordshire
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
Study officials:
affiliation: Center for Clinical Vaccinology and Tropical Medicine, University of Oxford
name: Susanne Hodgson, DPhil FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Bristol and Weston Foundation Trust
name: Rajeka Lazarus, DPhil FRCP
role: PRINCIPAL_INVESTIGATOR
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