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

Malaria,Falciparum Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06320535
• Other study ID #: VAC096
• Status: Recruiting
• Phase: Phase 1
• Start date: March 25, 2024
• Est. completion date: June 2027

Study information

• Verified date: February 2024
• Source: University of Oxford
• Contact: Volunteer Co-ordinators
• Phone: 01865611386
• Email: vaccinetrials[@]ndm.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: June 2027
• Est. primary completion date: June 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malaria, Falciparum
• Malaria,Falciparum

Intervention

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)
• 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)
• R21/Matrix M™ (Group 3)
10 mcg R21 in 50 mcg Matrix-M™ (D0) 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.

Locations

Country	Name	City	State
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Centre for Clinical Vaccinology and Tropical Meducine, Churchill Hospital, University of Oxford	Oxford	Oxfordshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	Bill and Melinda Gates Foundation, University Hospitals Bristol and Weston NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	(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
Primary	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 adverse events in each group	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
Primary	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
Primary	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