Safety and Immunogenicity of Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) - Full Text View

Sponsored by:	African Malaria Network Trust
Information provided by:	African Malaria Network Trust
ClinicalTrials.gov Identifier:	NCT00431808

Purpose

This study will be the first time that the candidate malaria vaccine Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) will be tested in malaria endemic populations. The phase Ib study will include adults who will be randomly allocated to either receive the malaria vaccine or the vaccine against Tetanus. Each participant will receive 3 immunizations, without the clinical investigators or the participants themselves knowing what has been given. They will then be follow-up up for immediate reactions to vaccination, and also over a longer term of one year. Blood will be taken to evaluate the biological safety parameters and also immune responses.

Condition	Intervention	Phase
Malaria	Biological: Malaria vaccine AMA1 (PfAMA-1-FVO[25-545] Biological: AMA1	Phase I

MedlinePlus related topics: Malaria Tetanus

Drug Information available for: Tetanus Vaccine Malaria Vaccines

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety Study
Official Title:	Randomized Controlled Trial to Evaluate the Safety and Immunogenicity of Recombinant Pichia Pastoris-Expressed P. Falciparum Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) Versus Tetanus Toxoid, in Healthy Malian Adult in Bandiagara

Further study details as provided by African Malaria Network Trust:

Primary Outcome Measures:

*Safety evaluation through: [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Solicited adverse events measured from day 0 to day 7 after each dose; [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
Unsolicited adverse events measured up to one month after each dose; [ Time Frame: 84 days ] [ Designated as safety issue: Yes ]
Serious Adverse Events measured during the 12 months of study duration. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Biological safety: two and four weeks after each vaccination, and thereafter every 12 weeks, in reference with the baseline before the first dose, by measuring the following : [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, WBC with differential counts, potassium, sodium, ASAT, ALAT, total bilirubin, alkaline phosphatase, γGT, creatinin [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

*Immunogenicity evaluation through: [ Time Frame: 84 days ] [ Designated as safety issue: No ]
The humoral response to the vaccine antigen: assessed by measuring the level of IgG by ELISA. [ Time Frame: 84 days ] [ Designated as safety issue: No ]
An IFA for at least two parasite strains will be used to verify that the antibodies elicited by the vaccine recognize the native protein on merozoites. [ Time Frame: 84 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	May 2007
Estimated Study Completion Date:	June 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
I, AMA1 vaccine: Experimental 20 volunteers will receive 3 doses of the vaccine	Biological: Malaria vaccine AMA1 (PfAMA-1-FVO[25-545] 3 doses of AMA 1 vaccine Biological: AMA1 50 micrograms of AMA1

Detailed Description:

This will be a randomized controlled trial to evaluate the Safety and Immunogenicity of recombinant pichia pastoris blood stage malaria vaccine Apical Membrane Antigen 1 (PfAMA-1-FVO[25-545]) versus tetanus toxoid, in healthy Malian adults in Bandiagara.

A phase Ia trial is currently ongoing and its interim results will be used to select the best dose/adjuvant combination to be brought to Africa. The trial is evaluating safety and immunogenicity of AMA-1 (10 µg or 50 µg) adjuvanted with aluminum hydroxide or Montanide ISA 720, or ASO2.

Primary objective:

- To evaluate the safety of one dose of AMA-1 (10 µg or 50 µg) adjuvanted with aluminum hydroxide or Montanide ISA 720, or ASO2, given at D0, D28 and D56 in healthy Malian adults.
Secondary Objectives:
- To assess the humoral response to the vaccine antigen by measuring the variation in the level of IgG and its ability to recognize the native protein on merozoites.
- To assess the cellular immune response by measuring the T cell proliferation and cytokine production following in vitro stimulation with the vaccine antigen.

The primary immunizations will be administered on days 0, 28 and a boost given at day 56. The participants will be followed up actively during the vaccination phase, and passively for one another 9 months. The will be 19 scheduled clinic visits and following will the the schedule for obtaining serology data D-28, D0, D28, D56, D84, D140 and D365

The primary evaluation will include the following:
- Solicited adverse events measured from day 0 to day 7 after each dose;
- Unsolicited adverse events measured up to one month after each dose;
- Serious Adverse Event (SAE) measured during the 12 months of study duration.
- Biological safety: two and four weeks after each vaccination, and thereafter every 12 weeks, in reference with the baseline before the first dose, by measuring the following RBC, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, WBC with differential counts, potassium, sodium, ASAT, ALAT, total bilirubin, alkaline phosphatase, γGT, creatinin.
Secondary evaluation criteria:
- The humoral response to the vaccine antigen: assessed by measuring the level of IgG by ELISA.
- An IFA for at least two parasite strains will be used to verify that the antibodies elicited by the vaccine recognize the native protein on merozoites
Statistical methods:

Descriptive methods shall be employed to evaluate the above criteria.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age 18-55 years inclusive at the time of screening
Residing in Bandiagara for the duration of the study
Separate written informed consent obtained before screening and study start, respectively
Available to participate in follow-up for the duration of study (14 months)
General good health based on history and clinical examination
Willingness not to become pregnant during the first five months of the study for female participants

Exclusion Criteria:

Previous vaccination with a investigational vaccine or a rabies vaccine
Use of a investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization, or planned use up to 30 days after the third immunization
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first immunization. This includes any dose level of oral steroids or inhaled steroids, but not topical steroids
Confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
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 vaccines components
History of splenectomy
Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25 times the upper limit of normal of the testing laboratory).
Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing).
Laboratory evidence of hematologic disease (absolute leukocyte count <4000/mm3 or >14,500/mm3, absolute lymphocyte count <1500/mm3, platelet count <120,000/mm3, or hemoglobin <10.0 g/dL).
Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period.
Simultaneous participation in any other interventional clinical trial
Acute or chronic pulmonary, cardiovascular, hepatic, renal or neurological condition, malnutrition, or any other clinical findings that in the opinion of the PI may increase the risk of participating in the study
Other condition that in the opinion of the PI would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00431808

Locations

Mali
Malaria Research and Training Center	Recruiting
Bandiagara, Mali
Contact: Mahamadou A Thera, MD MPH +223 221 6361 mthera@mrtcbko.org
Contact: Ogobara K Doumbo, MD PhD +223 222 8109 okd@ikatelnet.net
Sub-Investigator: Drissa Coulibaly, MD
Principal Investigator: Mahamadou A Thera, MD MPH
Principal Investigator: Mahamadou A Thera, MD MPH

Sponsors and Collaborators

African Malaria Network Trust

Investigators

Principal Investigator:	Mahamadou A Thera, MD MPH	Malaria Research and Training Center
Principal Investigator:	Mahamadou A Thera, MD MPH	Malaria Research and Training Center

More Information

Responsible Party:	African Malaria Network Trust ( Roma Chilengi )
Study ID Numbers:	AMA1_02_07, MU-08
Study First Received:	February 5, 2007
Last Updated:	April 1, 2008
ClinicalTrials.gov Identifier:	NCT00431808
Health Authority:	Mali: Ministry of Health

Keywords provided by African Malaria Network Trust:

Malaria
vaccine
Apical Membrane Antigene
Mali
Adults

Study placed in the following topic categories:

Protozoan Infections
Parasitic Diseases
Malaria
Healthy
Tetanus

Additional relevant MeSH terms:

Coccidiosis

ClinicalTrials.gov processed this record on January 16, 2009