A Phase Ia Study to Assess Safety and Immunogenicity of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in Healthy Adults Living in the UK
Overview
- Phase
- Early Phase 1
- Intervention
- Pfs48/45 in Matrix-M
- Conditions
- Malaria
- Sponsor
- University of Oxford
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Solicited Systemic Reactogenicity Signs and Symptoms for 7 Days Following Each Vaccination
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This is an open label, single-site, first-in-human, dose-escalation Phase Ia study to assess safety and immunogenicity of the Plasmodium falciparum malaria vaccine candidate Pfs48/45 in Matrix-M adjuvant in healthy adults living in the UK
Detailed Description
Volunteers will be recruited into one of three groups (n=8-10 per group) at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford over approximately 12 months. All volunteers will receive three dose of Pfs48/45 in 50 µg Matrix-M, administered intramuscularly and given four weeks apart. Enrolment will be staggered with clinical and safety reviews, follow-up visits and monitoring via a diary card.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adult aged 18 to 45 years.
- •Able and willing (in the Investigator's opinion) to comply with all study requirements.
- •Willing to allow the Investigators to discuss the volunteer's medical history with their GP.
- •Volunteers with the potential to become pregnant only: must practice continuous effective contraception for the duration of the study (see section 10.10).
- •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).
- •Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
- •Use of immunoglobulins or blood products (e.g., blood transfusion) in the last three months.
- •Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination.
- •Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- •Concurrent involvement in another clinical trial or planned involvement during the study period.
- •Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- •Any history of anaphylaxis in reaction to vaccinations.
Arms & Interventions
Group 1 - low dose
8-10 volunteers receiving three doses of 10 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm
Intervention: Pfs48/45 in Matrix-M
Group 2 - standard dose
8-10 volunteers receiving three doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm
Intervention: Pfs48/45 in Matrix-M
Group 3 - fractional dose
8-10 volunteers receiving two doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0 and 28, followed by one dose of 10 µg Pfs48/45 in 50 µg Matrix-M on day 56 via intramuscular injection (IM) in the deltoid region of the arm
Intervention: Pfs48/45 in Matrix-M
Outcomes
Primary Outcomes
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Solicited Systemic Reactogenicity Signs and Symptoms for 7 Days Following Each Vaccination
Time Frame: 7 days following each vaccination
Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results.
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Unsolicited Adverse Events (AEs) for 28 Days Following the Vaccination
Time Frame: 28 days following the vaccination
Number of unsolicited adverse events (AEs) for 28 days following the vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers. Assessed Through the Number of Participants With Abnormal Laboratory Test Results
Time Frame: 28 days following vaccination
Occurrence of change from baseline laboratory tests
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers Assessed Through the Number of Participants With Serious Adverse Events
Time Frame: Whole duration of the study (8 months following initial trial vaccination)
Occurrence of serious adverse events will be presented according to local grading scales
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers.
Time Frame: Whole duration of the study (8 months following initial trial vaccination)
Occurrence of AEs of special interest will be presented according to local grading scales and will be described in detail
Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Solicited Local Reactogenicity Signs and Symptoms for 7 Days Following Each Vaccination
Time Frame: 7 days following each vaccination
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results
Secondary Outcomes
- Humoral Immunogenicity of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers as Assessed by Humoral Responses to the Pfs48/45 Protein(Days 1, 29, 57, 140 and 240)
- Cellular Immunogenicity of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers as Assessed by Cellular Responses to the Pfs48/45 Protein(Days 1, 29, 57, 140 and 240)
- Ex Vivo Efficacy of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers Using Direct Membrane Feeding Assays as Assessed by Transmission-reducing Activity(Days 1, 29, 57, 140 and 240)
- Ex Vivo Efficacy of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers Using Direct Membrane Feeding Assays as Assessed by Transmission-blocking Activity(Days 1, 29, 57, 140 and 240)