Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children - Full Text View

Sponsors and Collaborators:	U.S. Army Office of the Surgeon General Kenya Medical Research Institute Walter Reed Army Institute of Research (WRAIR) The PATH Malaria Vaccine Initiative United States Agency for International Development (USAID) GlaxoSmithKline
Information provided by:	Walter Reed Army Institute of Research (WRAIR)
ClinicalTrials.gov Identifier:	NCT00317473

Purpose

To assess the safety and reactogenicity of the FMP-1/AS02A malaria vaccine in malaria-exposed children living in western Kenya and aged 12-47 months

Condition	Intervention	Phase
Plasmodium Falciparum Malaria	Biological: MSP-1 (FMP-1) with AS02A vs Imovax rabies vaccine	Phase I

MedlinePlus related topics: Malaria Rabies

Drug Information available for: Malaria Vaccines Rabies Vaccine Rabies Vaccines

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Dose Comparison, Parallel Assignment, Safety Study
Official Title:	Double-Blind,Randomized,Controlled,Dose Escalation Phase 1 Trial in 12-47 Month Old Children in Western Kenya to Evaluate the Safety and Immunogenicity of WRAIR’s MSP-1(FMP1) Malaria Vaccine Adjuvanted in GSK's AS02A Versus Rabies Vaccine.

Further study details as provided by Walter Reed Army Institute of Research (WRAIR):

Primary Outcome Measures:

Occurrence of solicited symptoms during a 7 day follow-up period after each vaccination (5 visits: day of vaccination and days 1, 2, 3, and 7)
Occurrence of unsolicited symptoms during a 30 day follow-up period after each vaccination (day of vaccination and the 29 subsequent days)
Occurrence of serious adverse events during an 8 month follow-up period following the first dose of study vaccine

Secondary Outcome Measures:

Antibody responses to MSP-1 by ELISA following immunization with the study vaccine through 364 days following the first dose of study vaccine

Estimated Enrollment:	135
Study Start Date:	August 2003
Estimated Study Completion Date:	September 2004

Detailed Description:

The study evaluates the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. The design is of an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. The setting is a rural population in Kombewa Division, western Kenya. The participants are 135 children aged 12-47 months and their mothers. The interventions are 10, 25 or 50 g of the falciparum malaria protein 1 (FMP1) formulated in 100, 250 and 500 L respectively of AS02A, or a comparator (Imovax® rabies vaccine). Outcome measures are safety and reactogenicity parameters and assessment of adverse events during solicited periods (7 days) and unsolicited periods (30 days) after each vaccination. Serious adverse events were monitored for 6 months after the last vaccination.

Eligibility

Ages Eligible for Study:	12 Months to 47 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

A healthy male or female child, 12 to 47 months of age at the time of screening.
Written informed consent obtained from at least one parent before study start.
Available to participate for the duration of the study (12 months).

Exclusion Criteria:

Acute disease at the time of entry into the study
Axillary temperature of 37.5C
Respiratory rate  50
Serum ALT  45 IU/l (i.e., > 1.5 X ULN)
Decreased renal function: serum creatinine levels > 92.2 mM/l (> 1.1 mg/dl).
Significant anemia (Hgb <8 gm/dL).
Thrombocytopenia (Platelets < 100,000 per mm3)
Impaired immunity: (Absolute lymphocyte count [ALC] for 1 year olds < 4.0 x 103/mm3; for 2 year olds < 3.0 x 103/mm3; for 3 year olds < 2.0 103/mm3.
History of homozygous sickle cell disease (SS).
Malnutrition (Z score; Malnutrition = Weight for height < - 3 z scores)
Blood transfusion or use of blood-based product in previous 6 months.
Prior receipt of a rabies vaccine or an investigational malaria vaccine.
Use of any investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use up to 30 days after the third dose.
Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. (For cortico-steroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
Administration or anticipated administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid.
Previous vaccination with a vaccine containing MPL or QS21 (e.g., RTS,S).
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. (No HIV testing will be undertaken as part of this study.)
History of allergic reactions or anaphylaxis to immunizations or to any vaccine components.
History of surgical splenectomy.
Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
Simultaneous participation in any other clinical trial.
Acute or chronic cardiovascular, pulmonary, hepatic or renal condition, which in the opinion of the PI may increase the risk to the subject from participating in the study.
Any other condition or circumstance that in the opinion of the investigator may pose a threat to the subject.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00317473

Locations

Kenya, Nyanza Province
Walter Reed Project Kombewa Clinic
Kombewa, Nyanza Province, Kenya

Sponsors and Collaborators

U.S. Army Office of the Surgeon General

Kenya Medical Research Institute

Walter Reed Army Institute of Research (WRAIR)

The PATH Malaria Vaccine Initiative

United States Agency for International Development (USAID)

GlaxoSmithKline

Investigators

Principal Investigator:

Mark R. Withers, M.D., MPH

USAMRU-K

More Information

Publications of Results:

Angov E, Aufiero BM, Turgeon AM, Van Handenhove M, Ockenhouse CF, Kester KE, Walsh DS, McBride JS, Dubois MC, Cohen J, Haynes JD, Eckels KH, Heppner DG, Ballou WR, Diggs CL, Lyon JA. Development and pre-clinical analysis of a Plasmodium falciparum Merozoite Surface Protein-1(42) malaria vaccine. Mol Biochem Parasitol. 2003 May;128(2):195-204.

Other Publications:

Pichyangkul S, Gettayacamin M, Miller RS, Lyon JA, Angov E, Tongtawe P, Ruble DL, Heppner DG Jr, Kester KE, Ballou WR, Diggs CL, Voss G, Cohen JD, Walsh DS. Pre-clinical evaluation of the malaria vaccine candidate P. falciparum MSP1(42) formulated with novel adjuvants or with alum. Vaccine. 2004 Sep 28;22(29-30):3831-40.

Ockenhouse CF, Angov E, Kester KE, Diggs C, Soisson L, Cummings JF, Stewart AV, Palmer DR, Mahajan B, Krzych U, Tornieporth N, Delchambre M, Vanhandenhove M, Ofori-Anyinam O, Cohen J, Lyon JA, Heppner DG; the MSP-1 Working Group. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine. 2006 Apr 5;24(15):3009-17. Epub 2005 Nov 28.

Stoute JA, Gombe J, Withers MR, Siangla J, McKinney D, Onyango M, Cummings JF, Milman J, Tucker K, Soisson L, Stewart VA, Lyon JA, Angov E, Leach A, Cohen J, Kester KE, Ockenhouse CF, Holland CA, Diggs CL, Wittes J, Gray Heppner D Jr; the MSP-1 Malaria Vaccine Working Group. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine. 2005 Dec 7; [Epub ahead of print]

Study ID Numbers:	WRAIR 1030, HSRRB Log No. A-12094, KEMRI SSC No. 761, HSPC No. HS171
Study First Received:	April 20, 2006
Last Updated:	April 24, 2006
ClinicalTrials.gov Identifier:	NCT00317473
Health Authority:	United States: Food and Drug Administration

Keywords provided by Walter Reed Army Institute of Research (WRAIR):

Vaccine
Phase 1
Plasmodium falciparum
Malaria
Merozoite surface protein-1

MSP-1
Falciparum malaria protein 1
FMP-1
AS02A

Study placed in the following topic categories:

Protozoan Infections
Rabies
Parasitic Diseases
Malaria
Malaria, Falciparum

Additional relevant MeSH terms:

Coccidiosis

ClinicalTrials.gov processed this record on January 16, 2009