Clinical trial NCT00317473: Phase 1 Trial of a Malaria Vaccine in Young Kenyan Children
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Plasmodium Falciparum Malaria
Keywords: Vaccine
Phase 1
Plasmodium falciparum
Malaria
Merozoite surface protein-1
MSP-1
Falciparum malaria protein 1
FMP-1
AS02A
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: Kenya Medical Research Institute
name: Walter Reed Army Institute of Research (WRAIR)
name: The PATH Malaria Vaccine Initiative (MVI)
name: United States Agency for International Development (USAID)
name: GlaxoSmithKline
First posted: 2006-04-24
Enrollment: 135
Sex: ALL
Minimum age (years): 12
Maximum age (years): 47
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

Detailed description: Study consists of 3 cohorts (12 to 23 months, 24 to 35 months, and 36 to 47 months). Within each cohort subjects were randomized in a 2:1 ration to receive one of three dose levels of FMP1/AS02A (Cohort A, 10 ug; Cohort B, 25 ug; Cohort C, 50 ug) or Imovax Rabies vaccine. Immunization was staggered among dose cohorts; subjects in Cohort B received their first immunization only after the Local Medical Monitor and Data Safety Monitoring Board reviewed Cohort A safety data for the eight-day follow-up period following their first immunization. The same procedure was followed for the immunization of Cohort C. This will be conducted in western Kenya a the Walter Reed Project Lumbewa Clinic.

Eligibility 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 degrees 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.

Primary outcomes:
measure: Occurrence of Solicited Symptoms During a 8 Day Follow-up Period After Each Vaccination
timeFrame: 40 days
measure: Occurrence of Unsolicited Symptoms During a 30 Day Follow-up Period After Each Vaccination
timeFrame: 90 days
measure: Occurrence of Serious Adverse Events During an 8 Month Follow-up Period Following the First Dose of Study Vaccine
timeFrame: 8 months
Secondary outcomes:
measure: Anti-FMP1 Antibody Titer Responses
timeFrame: 364 days
Other outcomes:
Locations:
city: Kombewa
country: Kenya
facility: Walter Reed Project Kombewa Clinic
state: Nyanza Province
Study officials:
affiliation: USAMRU-K
name: Mark R. Withers, M.D., MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/j.vaccine.2004.07.023.
citation: 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; 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. doi: 10.1016/j.vaccine.2005.11.028. Epub 2005 Nov 28.
citation: 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, Heppner DG Jr; 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. 2007 Jan 2;25(1):176-84. doi: 10.1016/j.vaccine.2005.11.037. Epub 2005 Dec 7.
citation: 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. doi: 10.1016/s0166-6851(03)00077-x.