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

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.

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