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

Phase 1

Completed

Conditions: Malaria

Interventions: Biological: Imovax Rabies Vaccine
Biological: FMP1/AS02A

Registration Number: NCT00308061

Lead Sponsor: U.S. Army Medical Research and Development Command

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imovax Rabies Vaccine	Imovax Rabies Vaccine	1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle
FMP1/AS02A Vaccine	FMP1/AS02A	500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Adverse Events by Immunization and Type	Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67	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.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Titers for Anti-FMP1 Antibody	Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364	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.