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

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.

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Biological: FMP1/AS02A; Biological: Imovax Rabies Vaccine

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mali
  • Bandiagara, Mali
    • Bandiagara Malaria Project

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FMP1/AS02A Vaccine; 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; 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.
Active Comparator: 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	Biological: Imovax Rabies Vaccine; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); GlaxoSmithKline; United States Agency for International Development (USAID); Walter Reed Army Institute of Research (WRAIR)
• Investigators: Principal Investigator: Mahamadou A Thera, MD MPH, University of Bamako Faculty of Medicine, Mali

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): September 1, 2004
• Study Completion (Actual): July 1, 2005

Study Registration Dates

• First Submitted: March 24, 2006
• First Submitted That Met QC Criteria: March 24, 2006
• First Posted (Estimate): March 28, 2006

Study Record Updates

• Last Update Posted (Actual): July 31, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; malaria; merozoite surface protein-1
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: WRAIR 1029; NIH DMID 02-184; Univ of Maryland IRB 0303311; HSRRB A-12093; NIAID IRB 177

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes