Clinical trial NCT00308061: Safety Study of Candidate Malaria Vaccine FMP1/AS02A in Healthy Adults in Bandiagara, Mali
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malaria
Keywords: Plasmodium falciparum
malaria
merozoite surface protein-1
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Walter Reed Army Institute of Research (WRAIR)
name: GlaxoSmithKline
name: United States Agency for International Development (USAID)
First posted: 2006-03-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Solicited Adverse Events by Immunization and Type
timeFrame: Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67
Secondary outcomes:
measure: Geometric Mean Titers for Anti-FMP1 Antibody
timeFrame: Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364
Other outcomes:
Locations:
city: Bandiagara
country: Mali
facility: Bandiagara Malaria Project
Study officials:
affiliation: University of Bamako Faculty of Medicine, Mali
name: Mahamadou A Thera, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Heppner DG Jr; MSP-1 Malaria Vaccine Working Group. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2007 Jan 2;25(1):176-84. doi: 10.1016/j.vaccine.2005.11.037. Epub 2005 Dec 7.
citation: Ockenhouse CF, Angov E, Kester KE, Diggs C, Soisson L, Cummings JF, Stewart AV, Palmer DR, Mahajan B, Krzych U, Tornieporth N, Delchambre M, Vanhandenhove M, Ofori-Anyinam O, Cohen J, Lyon JA, Heppner DG; MSP-1 Working Group. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2006 Apr 5;24(15):3009-17. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.
citation: Thera MA, Doumbo OK, Coulibaly D, Diallo DA, Kone AK, Guindo AB, Traore K, Dicko A, Sagara I, Sissoko MS, Baby M, Sissoko M, Diarra I, Niangaly A, Dolo A, Daou M, Diawara SI, Heppner DG, Stewart VA, Angov E, Bergmann-Leitner ES, Lanar DE, Dutta S, Soisson L, Diggs CL, Leach A, Owusu A, Dubois MC, Cohen J, Nixon JN, Gregson A, Takala SL, Lyke KE, Plowe CV. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial. PLoS One. 2008 Jan 23;3(1):e1465. doi: 10.1371/journal.pone.0001465.