A Study to Determine Whether 2 Investigational Malaria Vaccines Are Safe, Protective Against Malaria in Adults

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

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

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Biological: Group A FMP2.1/AS01B; Biological: Group B FMP2.1/AS02A

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Clinical Trials Center, Walter Reed Army Institute of Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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
• History of allergic disease or reactions to any vaccine
• Chronic or active neurologic disorders including seizures, excluding a single febrile seizure as a child
• History of splenectomy
• Acute disease at the time of enrollment (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature < 37.5°C/99.5°F).
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
• Personal medical histories including the following diagnoses: systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, vasculitis, and multiple sclerosis
• Seropositive for hepatitis B surface antigen or hepatitis C antibody
• Hepatomegaly, right upper quadrant abdominal pain or tenderness
• Elevated serum creatinine, defined in this study as greater than or equal to 1.7 mg/dL in males and 1.4 mg/dL in females
• Significant unexplained anemia: hematocrit < 35%
• Administration of immunoglobulins and/or any blood products within the three months preceding the first study immunization or planned administration during the study period
• Pregnant or lactating female or female who intends to become pregnant during the study
• Suspected or known current alcohol abuse as defined by the American Psychiatric Association in DSM IV (Diagnostic and Statistical Manual of Mental Disorders- 4th edition)
• Chronic or active illicit and/or intravenous drug use
• History of severe anaphylactic reactions to mosquito bites
• History of psoriasis (given its interaction with chloroquine)
• Any history of anaphylaxis in reaction to immunization
• History of allergy to nickel, imidazole or tetracycline group of antibiotics
• History of sickle cell disease or sickle cell trait
• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; FMP 2.1 50 μg FMP2.1/AS01B	Biological: Group A FMP2.1/AS01B; Other Names: FMP 2.1 50 μg FMP2.1/AS01B
EXPERIMENTAL: Group B; FMP 2.1 50 μg FMP2.1/AS02A	Biological: Group B FMP2.1/AS02A; Other Names: FMP 2.1 50 μg FMP2.1/AS02A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of adverse events	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti-AMA-1 antibody titers during Immunization Phase	Up to 70 days
Anti-AMA-I antibody titers during Challenge Phase	Up to 90 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Immunization Phase	Up to 70 days
Anti-AMA-I antibodies as percent parasite growth inhibition during Challenge Phase	Up to 90 days
Time to parasitemia development after primary challenge following administration of the FMP2.l/ASOIB and FMP2.l /AS02A	Up to 1 Year

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: GlaxoSmithKline; United States Agency for International Development (USAID); The PATH Malaria Vaccine Initiative (MVI)
• Investigators: Principal Investigator: Michele D. Spring, MD, M.S.P.H., Walter Reed Army Institute of Research (WRAIR)

Publications and helpful links

General Publications

• Dutta S, Lalitha PV, Ware LA, Barbosa A, Moch JK, Vassell MA, Fileta BB, Kitov S, Kolodny N, Heppner DG, Haynes JD, Lanar DE. Purification, characterization, and immunogenicity of the refolded ectodomain of the Plasmodium falciparum apical membrane antigen 1 expressed in Escherichia coli. Infect Immun. 2002 Jun;70(6):3101-10. doi: 10.1128/IAI.70.6.3101-3110.2002.
• Spring MD, Cummings JF, Ockenhouse CF, Dutta S, Reidler R, Angov E, Bergmann-Leitner E, Stewart VA, Bittner S, Juompan L, Kortepeter MG, Nielsen R, Krzych U, Tierney E, Ware LA, Dowler M, Hermsen CC, Sauerwein RW, de Vlas SJ, Ofori-Anyinam O, Lanar DE, Williams JL, Kester KE, Tucker K, Shi M, Malkin E, Long C, Diggs CL, Soisson L, Dubois MC, Ballou WR, Cohen J, Heppner DG Jr. Phase 1/2a study of the malaria vaccine candidate apical membrane antigen-1 (AMA-1) administered in adjuvant system AS01B or AS02A. PLoS One. 2009;4(4):e5254. doi: 10.1371/journal.pone.0005254. Epub 2009 Apr 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (ACTUAL): April 1, 2007
• Study Completion (ACTUAL): September 1, 2007

Study Registration Dates

• First Submitted: October 4, 2006
• First Submitted That Met QC Criteria: October 4, 2006
• First Posted (ESTIMATE): October 6, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): June 8, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: vaccine; efficacy; malaria; AMA-1 (apical membrane antigen-1)
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: WRAIR 1280; A-13949 (OTHER: WRAIR Protocol ID); ETrack Protocol No. 104936 (OTHER: E-Track); MAL-045 (OTHER: GSK); #20060900 (OTHER: Internal)