Safety Study of Candidate Malaria Vaccine FMP1/AS02A in Healthy Adults in Bandiagara, Mali

Study Overview
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Brief Summary
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This study tested the safety of a new malaria vaccine in adults in Mali, West Africa, and measured the ability of the vaccine to stimulate antibodies directed against the malaria protein that the vaccine is based on. Forty adults were randomly assigned to get either the experimental malaria vaccine or a rabies vaccine, for comparison.

Detailed Description
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The study was a randomized, controlled trial in which participants and clinical investigators were blinded to vaccine group assignment. Forty adults were randomized in a 1:1 ratio to receive either FMP1/AS02A or the control rabies vaccine. The aims of the control group were to account for baseline morbidity and the impact of seasonal malaria transmission on the dynamics of anti-MSP-1 antibodies, and to minimize bias in assessment of adverse events. Vaccines were given on a 0-, 1- and 2-month schedule. The first immunization was given in early July just as malaria transmission began; the second dose at the end of July as transmission was increasing; and the third dose in late August near the peak of malaria transmission intensity. Study day 90 was in October, shortly after transmission crests and when severe and uncomplicated malaria disease episodes peak, study day 180 was at the end of the malaria season, and study day 272 was at the height of the dry season. The final study follow-up on day 364 coincided with the beginning of the 2004 malaria season. Interim safety analyses were reviewed by an independent Safety Monitoring Committee before the second and third immunizations.

Official Title
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Double Blind Randomized Controlled Phase I Trial to Evaluate the Safety and Immunogenicity of WRAIR's MSP1 Candidate Malaria Vaccine (FMP1) Adjuvant in GSK Bio's AS02A vs. Rabies Vaccine in Semi-immune Adults in Bandiagara, Mali.

Conditions
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Malaria

Intervention / Treatment
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* Biological: FMP1/AS02A
* Biological: Imovax Rabies Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or non-pregnant female aged 18-55 years inclusive at the time of screening. For women, willingness not to become pregnant until 1 month after the last dose of vaccine Written informed screening and study consent obtained from the participant before study start. Available and willing to participate in follow-up for the duration of study (12 months) Exclusion Criteria: Previous vaccination with an investigational malaria vaccine or with any rabies vaccine. Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose. Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first vaccine dose. This will include oral steroids and inhaled steroids, but not topical steroids. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before the first dose of study vaccine(s) with the exception of tetanus toxoid. Previous vaccination with a vaccine containing MPL and/or QS-21 such as RTS,S. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. Any confirmed or suspected autoimmune disease History of allergic reactions or anaphylaxis to immunizations or to any vaccine component. History of serious allergic reactions to any substance, requiring hospitalization or emergent medical care History of allergy to tetracycline, doxycycline or neomycin History of splenectomy Serum ALT >=35 IU/L Serum creatinine level >133 micro moles per Liter (1.5 mg/dL) Hb <11 g/dL for males and <10 g/dL for females WBC <3.0 x 103/mm3 or >13.5 x 103/mm3 Absolute lymphocyte count <=1.0 x 103 per micro liter Thrombocytopenia < 100,000 per micro liter More than trace protein, more than trace hemoglobin or positive glucose in urine 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. Suspected or known current alcohol or illicit drug abuse. Pregnancy or positive urine beta-HCG on the day of or prior to immunization. Breastfeeding Simultaneous participation in any other interventional clinical trial. Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurologic condition, or any other findings that in the opinion of the PI may increase the risk to the participant from participating in the study. Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMP1/AS02A Vaccine<br>500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle | Biological: FMP1/AS02A<br>* FMP1 antigen contained 62.5 ug of lyophilized protein with 3.1 percent lactose as cryoprotectant. It's reconstituted in approx. 600 uL AS02A adjuvant manufactured by GSK. AS02A contains 50 ug MPL and 50ug QS21, 250uL of SB62 (oil/water emulsion) in phosphate buffered saline (PBS) per volume of 0.5 mL. All AS02A vials contained 0.65 to 0.75 mL of liquid.<br>|
| Active Comparator: Imovax Rabies Vaccine<br>1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle | Biological: Imovax Rabies Vaccine<br>* Sterile, stable, freeze-dried suspension of rabies virus prepared from the strain PM-1503-3M, obtained from the Wistar Inst. in Philadelphia. Each 1 mL dose of vaccine contained 100 mg of human albumin, <150g of neomycin sulfate, and >2.5 IU of rabies antigen.<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 by Immunization and Type | Number of participants with solicited adverse events by immunization and type (local, general and any) during each of the three eight-day follow-up periods after each vaccination (day of vaccination and post-vaccination days 1, 2, 3, and 7). Subjects were immunized on days 0, 30+7, and 60+7. | Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers for Anti-FMP1 Antibody | Immune response was measured by anti-FMP1 endpoint titers. Data were obtained on day 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364. Samples collected on vaccination days (days 0, 30, and 60) were collected immediately prior to vaccination. | Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasmodium falciparum, malaria, merozoite surface protein-1