A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK

Study 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.

Official Title
-----------------
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

Conditions
-----------------
Malaria, Plasmodium Falciparum

Intervention / Treatment
-----------------
* Biological: Pfs48/45 in Matrix-M


Participation Criteria
=================
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. Pregnancy, lactation or intention to become pregnant during the study. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). History of serious psychiatric condition that may affect participation in the study. Any other serious chronic illness requiring hospital specialist supervision. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 25 standard UK units every week. Suspected or known injecting drug abuse in the 5 years preceding enrolment. Hepatitis B surface antigen (HBsAg) detected in serum. Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless volunteer has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV ribonucleic acid (RNA) PCR at screening for this study). Volunteers unable to be closely followed for social, geographic or psychological reasons. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. In the event of abnormal test results, confirmatory repeat tests will be requested. Procedures for identifying laboratory values meeting exclusion criteria are shown in SOP VC027. Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Inability of the study team to contact the volunteer's GP to confirm medical history

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - low dose<br>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 | Biological: Pfs48/45 in Matrix-M<br>* Three doses of Pfs48/45 in Matrix-M at different doses<br>|
| Experimental: Group 2 - standard dose<br>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 | Biological: Pfs48/45 in Matrix-M<br>* Three doses of Pfs48/45 in Matrix-M at different doses<br>|
| Experimental: Group 3 - fractional dose<br>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 | Biological: Pfs48/45 in Matrix-M<br>* Three doses of Pfs48/45 in Matrix-M at different doses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess 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 | 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 | 7 days following each vaccination | 
| To assess 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 | 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 | 7 days following each vaccination | 
| To assess 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 | Occurrence of unsolicited adverse events (AEs) for 28 days following the vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results | 28 days following the vaccination | 
| To assess 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 | Occurrence of change from baseline laboratory tests | 28 days following vaccination | 
| To assess 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 | Occurrence of serious adverse events and will be presented according to local grading scales | Whole duration of the study (8 months following initial trial vaccination) | 
| To assess safety and tolerability of the Pfs48/45 with Matrix-M vaccine at various doses in healthy adult volunteers. | Occurrence of AEs of special interest and will be presented according to local grading scales and will be described in detail | Whole duration of the study (8 months following initial trial vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the 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 | Antibody responses to the Pfs48/45 protein will be assessed through total IgG isotypes and avidity | Days 1, 29, 57, 140 and 240 | 
| To assess the 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 | T cell responses to Pfs48/45 will be assessed by ex vivo enzyme-linked immunospot assays (ELISpot) | Days 1, 29, 57, 140 and 240 | 
| To assess 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 | Transmission-reducing activity | Days 1, 29, 57, 140 and 240 | 
| To assess 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 | Transmission-blocking activity | Days 1, 29, 57, 140 and 240 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pfs48/45, Matrix-M