Phase II AMA-1 Malaria Vaccine FMP2.1/AS02A Trial in Mali

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-05-31

Study Completion Date

2009-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Malaria is a disease that affects many people in Africa. Malaria is caused by germs spread by mosquito bites. The purpose of this study is to compare the number of children who get malaria after receiving an experimental malaria vaccine (FMP2.1/AS02A) to the number of children who get malaria after receiving a vaccine for rabies (an approved vaccine that does not prevent malaria). The children will be assigned to one of the vaccine groups by chance. Participants and doctors will not know which vaccine was given. Study participants will include 400 children, ages 1-6 years, living in Bandiagara, Mali. Children will receive 3 vaccine doses, by injection, to their upper arm. Study procedures will include physical exams and several blood samples. Participants will be involved in the study for 26 months.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Phase I Pediatric FMP2.1/AS02A Trial in Mali

NCT00358332

Plasmodium Falciparum Malaria

COMPLETED PHASE1

FMP2.1/AS02A: Rabies Vaccine Malaria-Experienced Adults in Bandiagara, Mali

NCT00349713

Malaria Plasmodium Falciparum Malaria

COMPLETED PHASE1

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

NCT00308061

Malaria

COMPLETED PHASE1

Phase I/II Trial of a Malaria Vaccine in Adults Living in the United States of America

NCT00312702

Malaria Plasmodium Falciparum Malaria

COMPLETED PHASE1/PHASE2

Double-blind, Randomized, Controlled Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine

NCT00223990

Malaria, Falciparum

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a randomized, controlled, phase II clinical trial to evaluate the efficacy, safety and immunogenicity of the apical membrane antigen-1 of Plasmodium (P.) falciparum (AMA-1) malaria vaccine FMP2.1/AS02A using rabies vaccine as a control in healthy children 1-6 years old in Bandiagara, Mali. This study is linked to DMID protocol 05-0146, which is a phase I dose escalation trial at the same site in the same population. In this study, 400 subjects will be randomized in a 1:1 ratio to receive either 50 micrograms of FMP2.1 in 0.5 mL AS02A or rabies vaccine. Immunizations will be given on days 0, 30 and 60. Solicited adverse events will be recorded on the days of immunization and at 1, 2, 3 and 7 days after each immunization. Unsolicited adverse events will be recorded for 30 days after each immunization. Passive case detection will be used to capture clinical malaria episodes and adverse events including serious adverse events, and will occur by continuous availability of clinical care in a population with high utilization of this care. Active surveillance will be used to capture malaria infections and adverse events including serious adverse events. For active case detection, following the third dose, participants will be followed monthly for 6 months and then at 12, 18 and 24 months after randomization, for clinical assessment, malaria smear and hemoglobin. Routine monthly malaria smears will not be read immediately unless symptoms are present. Children will be followed for 2 years after the first immunization. Sera will be collected for anti-FMP2.1 antibody titers on the days of immunization and 1, 3, 6, 8, 12, 18 and 24 months after the first immunization. Peripheral blood mononuclear cells (PBMCs) will be collected on the days of immunization, 30 days after the third immunization and 8, 12, 18 and 24 months after the first immunization. The study Final Report will be based on data collected up to 6 months after the assigned date of the third immunization. A supplemental report will include data from the entire 24-month observation period. Primary study objectives are to: determine the efficacy of FMP2.1/AS02A in children aged 1-6 years against first clinical malaria episodes (axillary temperature of greater than or equal to 37.5 degrees Celsius and parasitemia of greater than or equal to 2500/mm\^3) occurring between randomization and 6 months after the assigned date of the third immunization; and assess the safety of the vaccine in children aged 1-6 years. Secondary study objectives are to: describe the dynamics of anti-AMA-1 antibody responses in recipients of the malaria vaccine compared to natural responses in the control group; determine whether serum anti-AMA-1 IgG titer by enzyme linked immunosorbent assay (ELISA) 1 month after the third immunization correlates with protection against clinical malaria episode; measure allele-specific efficacy against parasites with AMA-1 genotypes homologous to and heterologous to the 3D7 clone of P. falciparum; determine vaccine efficacy against clinical malaria episodes occurring between randomization and 6 months after the assigned date of the third immunization; and if efficacy is observed based on the primary endpoint, to determine vaccine efficacy against first clinical malaria episode and all clinical episodes (using increasing parasitemia thresholds) occurring during 2 years after randomization.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Plasmodium Falciparum Malaria

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Rabies Vaccine

Rabies vaccine administered on Days 0, 30, and 60.

Group Type ACTIVE_COMPARATOR

Rabies Vaccine

Intervention Type BIOLOGICAL

White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.

FMP2.1/AS02A

50 mcg of FMP2.1 in 0.5 mL AS02A administered on Days 0, 30, and 60.

Group Type EXPERIMENTAL

FMP2.1/AS02A

Intervention Type BIOLOGICAL

3 doses administered a month apart: 50 µg recombinant subunit protein FMP2.1 (Plasmodium falciparum Apical Membrane Antigen-1 from strain 3D7 expressed in and purified from Escherichia coli), adjuvanted with 0.5 mL of AS02A (proprietary oil-in-water emulsion and phosphate buffered saline with the immunostimulants monophosphoral lipid A and QS21).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

FMP2.1/AS02A

3 doses administered a month apart: 50 µg recombinant subunit protein FMP2.1 (Plasmodium falciparum Apical Membrane Antigen-1 from strain 3D7 expressed in and purified from Escherichia coli), adjuvanted with 0.5 mL of AS02A (proprietary oil-in-water emulsion and phosphate buffered saline with the immunostimulants monophosphoral lipid A and QS21).

Intervention Type BIOLOGICAL

Rabies Vaccine

White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Age 1-6 years inclusive at the time of screening
* Residing in Bandiagara town
* Appear to be in generally good health based on clinical and laboratory investigation
* Separate written informed consent obtained from the parent/guardian before screening and study start, respectively
* Available to participate in follow-up for the duration of study (26 months)

Exclusion Criteria

* Previous vaccination with an investigational vaccine or a rabies vaccine
* Use of an 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 exclusion 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 tetracycline, doxycycline, nickel, Imidazole, eggs, neomycin, chlortetracycline or amphotericin B
* History of splenectomy
* Laboratory evidence of liver disease (alanine aminotransferase \[ALT\] greater than the upper limit of normal of the testing laboratory = 49.6 U/L)
* Laboratory evidence of renal disease (serum or plasma creatinine greater than 62 micro mol/L), or more than trace protein or blood on urine dipstick testing)
* Laboratory evidence of hematologic disease (absolute leukocyte count \<5,300/mm\^3 or \>15,300/mm\^3, absolute lymphocyte count \<2,300 mm\^3, platelet count \<133,000/mm\^3, or hemoglobin \<9.0 g/dL)
* Hepatitis B surface antigen positive
* Chronic skin condition that could interfere with vaccine site reactogenicity assessment
* 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 (including hepatomegaly), renal or neurological condition, severe 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 Principal Investigator (PI) would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol

Minimum Eligible Age

1 Year

Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes