Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children

Study Overview
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Brief Summary
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To assess the safety and reactogenicity of the FMP-1/AS02A malaria vaccine in malaria-exposed children living in western Kenya and aged 12-47 months

Detailed Description
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Study consists of 3 cohorts (12 to 23 months, 24 to 35 months, and 36 to 47 months). Within each cohort subjects were randomized in a 2:1 ration to receive one of three dose levels of FMP1/AS02A (Cohort A, 10 ug; Cohort B, 25 ug; Cohort C, 50 ug) or Imovax Rabies vaccine. Immunization was staggered among dose cohorts; subjects in Cohort B received their first immunization only after the Local Medical Monitor and Data Safety Monitoring Board reviewed Cohort A safety data for the eight-day follow-up period following their first immunization. The same procedure was followed for the immunization of Cohort C. This will be conducted in western Kenya a the Walter Reed Project Lumbewa Clinic.

Official Title
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Double-blind,Randomized,Controlled,Dose Escalation Phase 1 Trial in 12-47 Month Old Children in Western Kenya to Evaluate the Safety and Immunogenicity of WRAIR's MSP-1(FMP1) Malaria Vaccine Adjuvanted in GSK's AS02A Versus Rabies Vaccine.

Conditions
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Plasmodium Falciparum Malaria

Intervention / Treatment
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* Biological: FMP1/AS02A Malaria vaccine
* Biological: Imovax Rabies vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A healthy male or female child, 12 to 47 months of age at the time of screening. Written informed consent obtained from at least one parent before study start. Available to participate for the duration of the study (12 months). Exclusion Criteria: Acute disease at the time of entry into the study Axillary temperature of 37.5 degrees C Respiratory rate 50 Serum ALT 45 IU/l (i.e., > 1.5 X ULN) Decreased renal function: serum creatinine levels > 92.2 mM/l (> 1.1 mg/dl). Significant anemia (Hgb <8 gm/dL). Thrombocytopenia (Platelets < 100,000 per mm3) Impaired immunity: (Absolute lymphocyte count [ALC] for 1 year olds < 4.0 x 103/mm3; for 2 year olds < 3.0 x 103/mm3; for 3 year olds < 2.0 103/mm3. History of homozygous sickle cell disease (SS). Malnutrition (Z score; Malnutrition = Weight for height < - 3 z scores) Blood transfusion or use of blood-based product in previous 6 months. Prior receipt of a rabies vaccine or an investigational malaria vaccine. Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose. Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. (For cortico-steroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed). Administration or anticipated administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid. Previous vaccination with a vaccine containing MPL or QS21 (e.g., RTS,S). Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. (No HIV testing will be undertaken as part of this study.) History of allergic reactions or anaphylaxis to immunizations or to any vaccine components. History of surgical splenectomy. Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. Simultaneous participation in any other clinical trial. Acute or chronic cardiovascular, pulmonary, hepatic or renal condition, which in the opinion of the PI may increase the risk to the subject from participating in the study. Any other condition or circumstance that in the opinion of the investigator may pose a threat to the subject.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 47 Months

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMP1/AS02A Malaria vaccine 10ug<br>Subject vaccinated with 10 ug of FMP1/AS02A on days 0, 29 and 57 | Biological: FMP1/AS02A Malaria vaccine<br>* Subjects vaccinated with FMP1/AS02 vaccine<br>|
| Experimental: FMP1/AS02A Malaria vaccine 25 ug<br>Subject vaccinated with 25 ug of FMP1/AS02A on days 14, 42, and 70 | Biological: FMP1/AS02A Malaria vaccine<br>* Subjects vaccinated with FMP1/AS02 vaccine<br>|
| Experimental: FMP1/AS02A Malaria vaccine 50 ug<br>Subject vaccinated with 50 ug of FMP1/AS02A on days 28, 56 and 84 | Biological: FMP1/AS02A Malaria vaccine<br>* Subjects vaccinated with FMP1/AS02 vaccine<br>|
| Active Comparator: Imovax Rabies Vaccine<br>Subject vaccinated with Imovax Rabies Vaccine on corresponding FMP1/AS021 vaccination days | Biological: Imovax Rabies vaccine<br>* Subjects vaccinated on corresponding FMP1/AS02A vaccination days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Solicited Symptoms During a 8 Day Follow-up Period After Each Vaccination | Occurrence of any, local, or general solicited symptoms during the 8 day follow-up period | 40 days | 
| Occurrence of Unsolicited Symptoms During a 30 Day Follow-up Period After Each Vaccination | Occurrence of unsolicited symptoms during a 30 day follow-up period after each vaccination (day of vaccination and the 29 subsequent days) | 90 days | 
| Occurrence of Serious Adverse Events During an 8 Month Follow-up Period Following the First Dose of Study Vaccine | Occurrence of solicited and unsolicited serious adverse events during an 8 month follow-up period following the first dose of study vaccine | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-FMP1 Antibody Titer Responses | Antibody responses to FMP1 by ELISA following immunization with the study vaccine through 364 days following the first dose of study vaccine | 364 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Phase 1, Plasmodium falciparum, Malaria, Merozoite surface protein-1, MSP-1, Falciparum malaria protein 1, FMP-1, AS02A