Phase 1 Clinical Trial With Controlled Human Malaria Infection (CHMI) for Safety, Protective Efficacy, and Immunogenicity of Plasmodium Falciparum Malaria Protein (FMP014) Administered Intramuscularly With ALFQ Healthy Malaria-Naïve Adults
Overview
- Phase
- Phase 1
- Intervention
- FMP014
- Conditions
- Vaccine Reaction
- Sponsor
- U.S. Army Medical Research and Development Command
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Safety Dosage of Candidate Malaria Vaccine FMP014/ALFQ
- Last Updated
- 5 years ago
Overview
Brief Summary
A Phase 1, open label clinical study to evaluate the safety, immunogenicity, tolerability and efficacy of Plasmodium falciparum Malaria Protein 014 (FMP014) combined with (ALF with QS-21), saponin molecule derived from the bark of Quillaja species (ALFQ)) in healthy adult volunteers at different doses and dosing schedules.
Detailed Description
This is an open-label immunization with Controlled Human Malaria Infection (CHMI) study. Healthy, malaria-naïve adults, aged 18-55 years old will be recruited into one of 5 experimental cohorts in 2 parts. In Part A, 2 experimental cohorts of 5 subjects each will receive a series of 3 vaccinations at 0, 1, and 2 months at 2 doses (the "low dose" arm and the "high dose" arm). In Part B, 3 experimental cohorts of 10 subjects will receive a series of 3 vaccinations at 0, 1, 6 months (called the "delayed dose" arm), the "delayed fractional dose" arm is vaccinated at 0, 1, and 6 months with the 6 month dose being 1/5 the other doses, and the "standard" arm" at the 4th, 5th, and 6th month (after the first 2 vaccinations of the other 2 arms in Part B).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy adults between the ages 18-55 (inclusive);
- •Able and willing to provide written, informed consent;
- •Able and willing to comply with all research requirements, in the opinion of the Investigator;
- •Agreement to refrain from blood donation during the course of the study. Volunteers who have undergone CHMI can donate to other research once the study is complete but cannot donate to the American Red Cross for at least 3 years after the CHMI event;
- •Laboratory Criteria within 90 days before enrollment:
- •Hemoglobin ≥ 11.7 g/dL for women; ≥ 12.0 g/dL for men;
- •White Blood Cell count = 3,800-10,800 cells/mm3;
- •Platelets = 140,000-400,000/mm3;
- •Alanine aminotransferase (ALT; SGPT) 9-46 U/L male and 6-29 U/L female;
- •Serum creatinine ≤ 1.5 mg/dL;
Exclusion Criteria
- •History of malaria infection (any species) or residence in a malaria-endemic area for more than 5 years (includes previous participation in CHMI studies).
- •Previous travel to malaria endemic regions within the past 6 months before study enrollment defined as first vaccination or day of challenge (for infectivity controls) or planned travel to malaria endemic regions during the vaccination, CHMI and 28-day CHMI follow-up period; For Travel outside the US occurring 28 days post-challenge to a malaria endemic area exclusion will be at the discretion of the PI.
- •Any history of receiving a malaria vaccine.
- •Received an investigational product in the 30 days before enrollment, or planned to receive during the study period.
- •Concurrent participation in another clinical research study.
- •Any use of medications that prevent or treat malaria during the 1 month prior to challenge or planned use during the study (outside of the drugs provided by the study team).
- •Any serious medical illness or condition involving the heart, liver, lungs, or kidneys.
- •Any significant risk for developing heart disease in the next 5 years, assessed according to clinical Gaziano (NHANES I) criteria assessed at screening, and an ECG.
- •Receipt of immunoglobulins or blood products within 3 months before enrollment.
- •Any history of anaphylaxis.
Arms & Interventions
Part A - "Low" Dose
Part A vaccinees in the "low dose" arm will receive the lower dosing (20 μg FMP014 per 0.5 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month.
Intervention: FMP014
Part A - "Low" Dose
Part A vaccinees in the "low dose" arm will receive the lower dosing (20 μg FMP014 per 0.5 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month.
Intervention: ALFQ
Part A - "High" Dose
Part A vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month.
Intervention: FMP014
Part A - "High" Dose
Part A vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,2 month.
Intervention: ALFQ
Part B - "Standard" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 4,5,6 month.
Intervention: FMP014
Part B - "Standard" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 4,5,6 month.
Intervention: ALFQ
Part B - "Delayed" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month.
Intervention: FMP014
Part B - "Delayed" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month.
Intervention: ALFQ
Part B - "Delayed Fractional" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month.
Intervention: FMP014
Part B - "Delayed Fractional" Dose
Part B vaccinees in the "high dose" arm will receive the lower dosing (40 μg FMP014 per 1.0 mL ALFQ) approximately 2 weeks prior to each vaccination. Vaccination to be delivered on 0,1,6 month.
Intervention: ALFQ
Outcomes
Primary Outcomes
Safety Dosage of Candidate Malaria Vaccine FMP014/ALFQ
Time Frame: 393 Days (+/- 14)
To assess the safety of candidate malaria vaccine FMP014/ALFQ. Safety dosage as indicated by incidence of solicited adverse events and serious adverse events through the end of the study.
Assess expected immunological response associated with Candidate Malaria Vaccine FMP014/ALFQ
Time Frame: 393 Days (+/- 14)
Measuring the number of local (signs and symptoms) adverse events reported by candidates receiving the candidate malaria vaccine FMP014/ALFQ.
Secondary Outcomes
- Measure (Qualitative) Immune Responses to CSP, induced by FMP014/ALFQ using various immunoassays.(505 Days (+/- 14))
- Determine the number of days before Plasmodium falciparum infection in controlled humans vaccinated with FMP014/ALFQ(505 Days (+/- 14))
- Measure (Quantitative) Immune Responses to CSP, induced by FMP014/ALFQ using various immunoassays.(505 Days (+/- 14))