Phase I Pediatric FMP2.1/AS02A Trial in Mali
Information source: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Plasmodium Falciparum Malaria
Intervention: FMP2.1/AS02A (Biological); Rabies vaccine (RabAvert) (Biological)
Phase: Phase 1
Status: Completed
Sponsored by: U.S. Army Medical Research and Materiel Command
Summary
The purpose of this study is to test the safety and dosages of a malaria vaccine in 100
children, 1-6 years old, in Bandiagara, Mali. The study is testing the safety of the vaccine
when it is given to people who are regularly exposed to malaria and it will provide
information regarding optimal vaccine dosage. This study will compare 3 injections of
different vaccine doses to a rabies vaccine that is already approved. During the study, the
child's health will be checked in the clinic and during home visits. Children may
participate for about 14 months, and blood will be taken from each child throughout the
study. If the child becomes sick from malaria, he/she will be treated. Information from this
study may be used to develop a malaria vaccine that will help control the disease.
Clinical Details
Official title: Randomized, Controlled, Dose Escalation Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of WRAIR's AMA-1 Malaria Vaccine (FMP2.1) Adjuvanted in GSKBio's AS02A Vs. Rabies Vaccine in 1-6 Year Old Children in Bandiagara, Mali
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention
Primary outcome: Occurrence of Solicited Systemic Symptoms During a 7-day Surveillance Period (Systematically Collected) Following Vaccinations at Days 0, 30, and 60.Occurrence of Unsolicited Symptoms During a 30-day Surveillance Period Following Vaccinations at Days 0, 30, and 60. Number of Subjects Spontaneously Reporting Any Serious Adverse Event. Occurrence of Solicited Local Symptoms During a 7-day Surveillance Period (Systematically Collected) Following Vaccinations at Days 0, 30, and 60.
Secondary outcome: Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 0Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 30 Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 60 Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 90 Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 180 Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 272. Anti-FMP2.1 Antibody Titers Measured by ELISA, at Day 364
Detailed description:
This study is a randomized, controlled, dose-escalation, phase I trial of the FMP2. 1/AS02A
malaria vaccine, using rabies vaccine as a control. This study is linked to DMID protocol
07-0003. The primary objective of this study is to evaluate the safety and reactogenicity of
FMP2. 1/AS02A in children naturally exposed to P. falciparum malaria infection. The secondary
objective is to measure the magnitude and duration of antibody response to FMP2. 1 by
enzyme-linked immunosorbent assay (ELISA). One hundred healthy children aged 1-6 years in
Bandiagara, Mali, will be randomized to 1 of 3 possible groups. Twenty subjects will be
enrolled in cohort 1 and 40 subjects each in cohorts 2 and 3. Children within each cohort
will be randomized in a 3: 1 ratio to receive 10, 25 or 50 micrograms of FMP2. 1 (in cohorts
1, 2 and 3, respectively) adjuvanted with a proportionate volume of the AS02A, or rabies
vaccine. Thus a total of 75 children will receive the malaria vaccine and 25 the rabies
vaccine. Immunizations will be given on days 0, 30 and 60 in a staggered fashion, with the
first administrations of the 25 and 50 microgram dose levels of FMP2. 1 following the first
administration of the 10 and 25 microgram dose levels, respectively, by 2-3 weeks. Solicited
adverse events will be recorded on the days of immunization and days 1, 2, 3 and 7 after
each immunization, and unsolicited adverse events will be recorded for 30 days after each
immunization. Children will be followed for 1 year after the last immunization. Sera will be
collected for anti-FMP2. 1 antibody titers on the days of immunization and 14 days after each
immunization as well as 3, 6, 9 and 12 months after the first immunization. Each child will
participate in the study for up to 414 days, which includes the screening period. The
primary outcome measures include: occurrence of solicited symptoms after each vaccination
during a 7-day surveillance period (day of vaccination and days 1, 2, 3 and 7 after
vaccination), occurrence of unsolicited symptoms after each vaccination during a 30-day
surveillance period (day of vaccination and 30 subsequent days); and occurrence of serious
adverse events throughout the study period. The secondary outcome measure is titers and
activity of anti-FMP2. 1 antibody at each time point where serology samples are analyzed,
measured by ELISA.
Eligibility
Minimum age: 1 Year.
Maximum age: 6 Years.
Gender(s): Both.
Criteria:
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 (14 months).
Exclusion Criteria:
- Previous vaccination with an 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 tetracycline, doxycycline, nickel or Imidazole.
- 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 creatinine greater than the upper limit
of normal of the testing laboratory = 0. 5 mg/dL (44. 2 micromol/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).
- 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, renal or neurological condition,
severe malnutrition, or any other clinical findings that in the opinion of the
Principal Investigator (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.
Locations and Contacts
University of Bamako, Malaria Research and Training Center, Bamako, Mali
Additional Information
Starting date: November 2006
Last updated: October 18, 2011
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