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

October 11, 2018 updated by: U.S. Army Medical Research and Development Command

Randomized, Controlled Phase II Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the AMA-1 Malaria Vaccine FMP2.1/AS02A Versus Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mali
      • Bamako, Mali
        • University of Bamako, Malaria Research and Training Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 6 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Rabies Vaccine
Rabies vaccine administered on Days 0, 30, and 60.
Biological: Rabies Vaccine
White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.
Experimental: FMP2.1/AS02A
50 mcg of FMP2.1 in 0.5 mL AS02A administered on Days 0, 30, and 60.
Biological: 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).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the First Vaccination
Time Frame: 0-7 days after first vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after each vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
0-7 days after first vaccination
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Second Vaccination.
Time Frame: 0-7 days after the second vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
0-7 days after the second vaccination
Number of Subjects Reporting Solicited Adverse Events During the 7-day Surveillance Period After the Third Vaccination.
Time Frame: 0-7 days after the third vaccination
Solicited symptoms were recorded by study staff at clinic visits on Days 0, 1, 2 and 7 after vaccination. "Reported Limitation of Arm Motion" refers to the parents' report of the symptom while "Limitation of Arm Motion" refers to the clinicians' assessment of the symptom, collected separately.
0-7 days after the third vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the First Vaccination
Time Frame: Day 0-29 after first vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Day 0-29 after first vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Second Vaccination
Time Frame: Day 0-29 after second vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Day 0-29 after second vaccination
Number of Unsolicited Non-serious Adverse Events Reported During the 30-day Surveillance Period After the Third Vaccination
Time Frame: Day 0-29 after third vaccination
Unsolicited non-serious adverse events reported are those occurring within 30 days after vaccination. The categories are the MedDRA System Organ Classes for which at least one adverse event was reported. All non-serious adverse events are included, regardless of severity or relationship to vaccination.
Day 0-29 after third vaccination
Time to First Clinical Malaria Episode With Significant Parasitemia (2500/mm^3) and Temperature of Greater Than or Equal to 37.5 Degrees C.
Time Frame: Occurring between randomization and 6 months after the assigned date of the 3rd immunization.
Time to first clinical malaria episode is displayed in a life table format to display the number of subjects at risk, the number with first clinical episode and the number censored at each time point.
Occurring between randomization and 6 months after the assigned date of the 3rd immunization.
Number of Subjects Reporting Serious Adverse Events
Time Frame: 24 months after initial vaccination
A serious adverse event was defined as any untoward medical occurrence that results in death, is life threatening, results in persistent or significant disability/incapacity, requires in-patient hospitalization or prolongation of existing hospitalization or is a congenital anomaly/birth defect in the offspring of a study subject. In addition, important medical events that may jeopardize the participant or may require intervention to prevent one of the other outcomes listed above was considered serious.
24 months after initial vaccination

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence Density of Clinical Malaria Episode
Time Frame: Between randomization and 6 months after 3rd immunization.
Clinical malaria episode was defined by significant parasitemia (2500/mm^3) and temperature of greater than or equal to 37.5 degrees C. Event rate was determined by dividing the number of episodes (150 for the Rabies group and 121 for the FMP2.1/ASO2A group) by the number of Person Years at Risk (PYAR) (126.341 for Rabies group and 127.411 for the FMP2.1/ASO2A group).
Between randomization and 6 months after 3rd immunization.
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by Enzyme Linked ImmunoSorbent Assay (ELISA) at Day 0
Time Frame: Day 0
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 0 prior to the first vaccination.
Day 0
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 30.
Time Frame: Day 30 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 30, prior to the second vaccination.
Day 30 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 60.
Time Frame: Day 60 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 60, prior to the third vaccination.
Day 60 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 90.
Time Frame: Day 90 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 90.
Day 90 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 150.
Time Frame: Day 150 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 150.
Day 150 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 240.
Time Frame: Day 240 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 240.
Day 240 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 364
Time Frame: Day 364 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 364.
Day 364 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 547
Time Frame: Day 547 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 547.
Day 547 after initial vaccination
Geometric Mean Titers of Anti-FMP2.1 Antibody Measured by ELISA at Day 730
Time Frame: Day 730 after initial vaccination
Titers of Anti-FMP2.1 antibody were determined by ELISA from sera collected at Day 730.
Day 730 after initial vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
U.S. Army Medical Research and Development Command

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)
GlaxoSmithKline
University of Maryland
Walter Reed Army Institute of Research (WRAIR)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mahamadou A Thera, MD, MPH, University of Bamako

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2009

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2009

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 12, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 16, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 9, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 07-0003
  • U01AI065683 (U.S. NIH Grant/Contract)
  • 2U01AI065683-06 (U.S. NIH Grant/Contract)
  • Malaria-056 (110060) (Other Identifier: GSK)
  • HSRRB # A-14262 (Other Identifier: USAMRMC)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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