Phase I/IIa Study of the Safety, Immunogenicity and Preliminary Efficacy After Sporozoite Challenge of FMP2.1/AS01B and FMP2.1/AS02A Candidate Malaria Vaccines Administered Intramuscularly at Months 0, 1, and 2 in Malaria-naive Adults Living in the United States
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Malaria
- Sponsor
- U.S. Army Medical Research and Development Command
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Number of adverse events
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this study is to determine whether 2 investigational malaria vaccines are safe as well as protective against malaria in adults living in the United States
Detailed Description
35 volunteers aged 18 to 50 years will be enrolled to receive one of 2 investigational malaria vaccines. The vaccines are made of a malaria protein FMP2.1 mixed in 2 different adjuvants (AS01B and AS02A). Five volunteers will get a small (10 µg) dose of FMP2.1/AS01B since this vaccine has not yet been in humans. If it is safe, then 15 volunteers will get 50 µg FMP2.1 in AS02A and 15 will get 50 µg FMP2.1 in AS01B. All vaccines are given IM in the deltoid of the non-dominant arm, every 1 month for 3 months. After vaccination, the subjects will follow up at clinical trials for evaluation of any adverse events. 20 vaccinees (10 from each 50 µg vaccine group) will undergo primary sporozoite challenge 14-30 days after dose 3 via bite of 5 malaria-infected mosquitoes. All subjects will have a blood slide prepared and read to check for asexual P. falciparum parasitemia at least once daily beginning day 5 post challenge. Beginning on day 10 post challenge, subjects will check into a designated hotel, where 24 hour evaluation and care will be available for 10 nights. After this hotel phase, there will be follow-up visits to ensure there are no late developments of malaria in those who have not fallen ill (and thus are considered protected). Any subject who tests positive for malaria will be treated with chloroquine. Efficacy readouts are complete protection or significant delay in patency defined as \>2 days than the median prepatent period for the 6 infectivity controls. These 6 controls receive no vaccine and are enrolled for malaria-challenge only in order to provide comparison group for vaccinated individuals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A male or non-pregnant female 18 to 50 years of age (inclusive) at the time of screening
- •Written informed consent obtained from the participant before screening procedures
- •Free of clinically significant health problems as established by medical history and clinical examination before entering into the study\*
- •Available to participate for duration of study (approximately five months, not including screening)
- •If the participant is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (e.g., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant® or Depo-Provera®) during this study, have a negative pregnancy test at the time of each immunization, and must agree to continue such precautions for two months after completion of the immunization series and the malaria challenge.
- •Prior to entry into this study, participants must score at least 80% correct on a short multiple-choice quiz that assesses their understanding of this study. If they do not score 80% on the initial quiz, the protocol information will be reviewed with them to ensure comprehension and they will have the opportunity to retest. Participants who fail the Comprehension Assessment for the second time will not be enrolled.
Exclusion Criteria
- •Prior receipt of an investigational malaria vaccine
- •Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first study immunization or planned use during the study period, or receipt of investigational vaccine containing 3-D MPL and/or QS-21 at any time in the past (Have you received an experimental vaccine with a GSK adjuvant in the past?)
- •Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of immunization. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- •Chronic use of antibiotics with anti-malarial effects (e.g., tetracyclines for dermatologic patients, sulfa for recurrent urinary tract infections, etc.)
- •Planned administration of a vaccine not foreseen by the study protocol 30 days prior to or after the first immunization
- •History of malaria chemoprophylaxis within 60 days prior to immunization
- •Any history of malaria
- •Known exposure to malaria within the previous 12 months
- •Planned travel to malarious areas during the study period
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
Outcomes
Primary Outcomes
Number of adverse events
Time Frame: Up to 1 year
Secondary Outcomes
- Anti-AMA-I antibodies as percent parasite growth inhibition during Immunization Phase(Up to 70 days)
- Time to parasitemia development after primary challenge following administration of the FMP2.l/ASOIB and FMP2.l /AS02A(Up to 1 Year)
- Anti-AMA-I antibodies as percent parasite growth inhibition during Challenge Phase(Up to 90 days)
- Anti-AMA-1 antibody titers during Immunization Phase(Up to 70 days)
- Anti-AMA-I antibody titers during Challenge Phase(Up to 90 days)