Evaluate the Safety and Efficacy of Plasmodium Falciparum Malaria Protein 010 (FMP010) Administered With Adjuvant AS01B

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an investigational malaria vaccine is safe and induces an immune response against malaria when tested in adults living in the United States.

Detailed Description
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Study is to evaluate the safety, reactogenicity, and immunogenicity fo the candidate Plasmodium falciparum malaria protein 10 (FMP010). Malaria-experienced adults will be enrolled and randomized into 2 groups. Subjects will receive full dose FMP010 antigen (approximately 50 μg) in 0.5 mL AS01B adjuvant or licensed rabies vaccine Rabipur (by Novartis) supplied in single dose vials containing lyophilized antigen with 1.0 mL of diluent (sterile water) for injection.

Official Title
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Phase 1b Controlled Double Blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of the Candidate Plasmodium Falciparum Malaria Protein 010 (FMP010) Administered Intramuscularly With Glaxo Smith Kline (GSK) Biologicals' Adjuvant AS01B

Conditions
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Malaria

Intervention / Treatment
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* Biological: Plasmodium falciparum Malaria Protein 010 (FMP010)
* Biological: Rabipur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • A male or non-lactating female 18 to 50 years of age (inclusive) at the time of screening Free of significant health problems as established by medical history and clinical examination before entering into the study Available to participate for duration of study (approximately seven months) If the subject is female, she must be of non-childbearing potential (either surgically sterilized or one year post-menopausal) or, if of childbearing potential, she must have a negative pregnancy test at the time of vaccination, be capable of preventing pregnancy for at least one month prior to determination of eligibility (to include abstinence or contraceptives (for example intrauterine contraceptive device; oral contraceptives; Norplant® or Depo-Provera® ), and must agree to continue such precautions for two months after completion of the vaccination series. Written informed consent must be obtained from the subject before screening procedures. Exclusion Criteria: • Prior receipt of any investigational malaria vaccine Prior receipt of a vaccine containing either QS-21, MPL or AS02A or AS01B Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period Administration of chronic (defined as more than 14 days) immunosuppressants or other immune modifying drugs within six months of vaccination. For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed. Planned administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of the study vaccine. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection A family history of congenital or hereditary immunodeficiency Chronic or active neurologic disease including seizure disorder History of splenectomy Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or abnormal baseline laboratory screening tests ALT above normal range Creatinine above normal range Hemoglobin below normal range Platelet count below normal range Total white cell count below normal Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness, such as diarrhea or mild upper respiratory infection without fever, i.e. Oral temperature < 37.5°C. Hepatomegaly, right upper quadrant abdominal pain or tenderness Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period Pregnant or lactating female Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination Female who is willing or intends to become pregnant during the study Any history of allergic reaction or anaphylaxis to previous vaccination Unwilling to allow blood samples to be stored for future use Inability to make follow up visits Allergy to kanamycin, nickel, or imidazole Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study Previous allergy to Rabies Vaccine Allergy to chicken and chicken products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 µg of FMP010 antigen in 0.5 mL AS01B adjuvant<br>50 µg of FMP010 antigen in 0.5 mL AS01B adjuvant given intramuscularly in the deltoid muscle of the non-dominant arm. | Biological: Plasmodium falciparum Malaria Protein 010 (FMP010)<br>* Vaccine antigen is a recombinant protein based on merozoite surface protein-1 (MSP-1) of FVO strain of Plasmodium falciparum, and adjuvant AS01B is a proprietary adjuvant of GSK<br>|
| Experimental: Rabies Vaccine Rabipur<br>Rabies Vaccine Rabipur given intramuscularly in the deltoid muscle of the non-dominant arm. | Biological: Rabipur<br>* Rabipur is a licensed rabies vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Adverse Events With Each Vaccination by Grade | Vaccinations were given at 0-, 1-, 2-month interval, occurrence and intensity of solicited symptoms on day of vaccination (Day 0) and Days 1-7 after each vaccination Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe | After each vaccination (Day 0), follow-up visits were scheduled on Days 1, 2, 3, and 7 | 
| Number of Subjects With Unsolicited Adverse Events at Specified Grades | Vaccinations were given at 0-, 1-, 2-month interval, number of subjects reporting unsolicited symptoms at specified grades over a 30-day follow-up period (day of vaccination and 29 subsequent days) after each vaccination Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe | After each vaccination (Day 0), 30 day f/u period post vaccination | 
| Number of Subjects With the Occurrence of Serious Adverse Events | Vaccinations were given at 0-, 1-, 2-month interval, number of subjects with the occurrence of serious adverse events at days 0-7 post vaccination | After each vaccination (Day 0), follow-up visits were scheduled on Days 1, 2, 3, and 7 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Titers Per Subject by Enzyme Linked Immunosorbent Assay in 50 µg Dose Group | Antibody concentrations will be presented by reporting the summarized Geometric Mean Titer (GMT) values with 95% Confidence Interval (CI) (not presented in results), at each time point at which blood samples are taken for serology. Peak responses (Day 70) will be compared by Student's T test on data normalized by log transformation to ascertain presence or absence of significant dose response difference. GMTs are presented without CI data. | After each vaccination, blood draws performed on Days 0, 14, 28, 42, 56, 70 and 112 | 
| Antibody Titers Per Subject by Enzyme Linked Immunosorbent Assay in Rabies Vaccine Group | Antibody concentrations will be presented by reporting the summarized Geometric Mean Titer (GMT) values with 95% Confidence Interval (CI) at each time point at which blood samples are taken for serology. Peak responses (Day 70) will be compared by Student's T test on data normalized by log transformation to ascertain presence or absence of significant dose response difference. GMTs are presented without CI data. | After each vaccination, blood draws performed on Days 0, 14, 28, 42, 56, 70 and 112 |