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

Primary Purpose

Malaria

Status
Completed
Phase
Phase 1
Locations
Mali
Study Type
Interventional
Intervention
FMP1/AS02A
Imovax Rabies Vaccine
Sponsored by
U.S. Army Medical Research and Development Command
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring Plasmodium falciparum, malaria, merozoite surface protein-1

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Bandiagara Malaria Project

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

FMP1/AS02A Vaccine

Imovax Rabies Vaccine

Arm Description

500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle

1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
March 24, 2006
Last Updated
May 3, 2017
Sponsor
U.S. Army Medical Research and Development Command
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline, United States Agency for International Development (USAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00308061
Brief Title
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

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
September 2004 (Actual)
Study Completion Date
July 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
U.S. Army Medical Research and Development Command
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline, United States Agency for International Development (USAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Plasmodium falciparum, malaria, merozoite surface protein-1

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FMP1/AS02A Vaccine
Arm Type
Experimental
Arm Description
500 uL of FMP1/AS02A is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle
Arm Title
Imovax Rabies Vaccine
Arm Type
Active Comparator
Arm Description
1 mL of Imovax Rabies Vaccine is given to subject on days 0, 30+7, and 60+7 in the left deltoid muscle
Intervention Type
Biological
Intervention Name(s)
FMP1/AS02A
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Imovax Rabies Vaccine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Solicited Adverse Events by Immunization and Type
Description
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.
Time Frame
Days 0, 1, 2, 3, 7, 30, 31, 32, 33, 37, 60, 61, 62, 63, 67
Secondary Outcome Measure Information:
Title
Geometric Mean Titers for Anti-FMP1 Antibody
Description
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.
Time Frame
Days 0, 14, 30, 44, 60, 74, 90, 180, 272, and 364

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mahamadou A Thera, MD MPH
Organizational Affiliation
University of Bamako Faculty of Medicine, Mali
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bandiagara Malaria Project
City
Bandiagara
Country
Mali

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16388879
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.
Results Reference
background
PubMed Identifier
16356603
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.
Results Reference
background
PubMed Identifier
18213374
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.
Results Reference
derived

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

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