Clinical trial NCT00197028: Examine Safety and Immune Responses of GSK 257049 Vaccine When Administered to Infants Living in a Malaria-endemic Region
Official title: A Phase I/IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02D, a Candidate Malaria Vaccine in Infants Living in a Malaria-endemic Region
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 214
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: GSK Biologicals is developing in partnership with the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative a candidate malaria vaccine for the routine immunization of infants and children living in malaria endemic areas. The vaccine would offer protection against malaria disease due to the parasite Plasmodium falciparum. The vaccine would also provide protection against infection with hepatitis B virus (HBV).

This trial is being carried out following the demonstration of efficacy of a previous version of the malaria candidate vaccine in children in Mozambique: there, the vaccine demonstrated approximately 30% efficacy against clinical episodes of malaria and approximately 58% efficacy against severe malaria disease.

In order to integrate the malaria vaccine into the Expanded Program on Immunization (EPI) regimen, in malaria-endemic regions, for this trial, a 0.5 ml dose of GSK 257049 vaccine has been developed. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: All infants participating in this phase I/IIb study will receive TETRActHib (a licensed diphtheria-tetanus-pertussis Haemophilus influenzae vaccine manufactured by Aventis Pasteur) by IM injection in their right thigh at 8, 12, and 16 weeks; They will be randomized to receive either the candidate malaria vaccine, GSK 257049 vaccine (0.5 ml dose) or Engerix-B (a licensed hepatitis B vaccine manufactured by GSK Biologicals) by IM injection in their left thigh at 10, 14, 18 weeks. Infants will be followed-up daily for 7 days after each vaccine dose for evaluation of safety and reactogenicity. There will be a 14-day follow-up period after each dose of TETRActHib and after Dose 1 and Dose 2 of GSK 257049 vaccine or Engerix-B, and a one month follow-up period after Dose 3 of GSK 257049 vaccine or Engerix-B for reporting unsolicited symptoms. Serious adverse events will be recorded throughout the 14 month study period. A small amount of blood (2 ml = 1/2 teaspoon) will be obtained at four different time points to measure the immune response elicited by the vaccines administered during this study period. Preliminary indication of vaccine efficacy in this age group will be established by actively monitoring for infection with Plasmodium falciparum.

Eligibility criteria: Inclusion Criteria:

* A male or female infant of between 6 and 12 weeks of age at the time of first vaccination.
* Written informed consent obtained from the parent(s) or guardian(s) of the subject
* Free of obvious health problems as established by medical history and clinical examination before entering into the study.
* Born to a mother who is hepatitis B surface antigen (HBsAg) negative and human immunodeficiency virus (HIV) negative.
* Born after a normal gestation period (between 36 and 42 weeks).
* Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.

Exclusion Criteria:

* Bacillus Calmette-Guérin tuberculosis vaccine (BCG) administration within one week of proposed administration of a study vaccine.
* Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth
* Any chronic drug therapy to be continued during the study period.
* Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus influenzae type b or hepatitis B vaccines.
* Major congenital abnormality.
* Serious acute or chronic illness determined by clinical, physical examination and laboratory screening tests
* Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination
* A family history of congenital or hereditary immunodeficiency.
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
* History of any neurological disorders or seizures.
* Maternal death.
* Hemoglobin \< 80 g/L
* Simultaneous participation in any other clinical trial.
* Same sex twin
* Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trialModerate malnutrition at screening

Primary outcomes:
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 to Month 6
Secondary outcomes:
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: Throughout the entire study period (from Month 0 to Month 14)
measure: Concentrations of Antibodies Against Hepatitis B (Anti-HB)
timeFrame: Prior to vaccination at Month 0 (PRE) and 1 month post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 104).
measure: Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
timeFrame: Prior to vaccination at Month 0 (PRE), 1 month post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 104) and 3½ months post Dose 3 of Engerix-B® or RTS,S/AS02D vaccine (Day 180).
measure: Concentrations of Antibodies Against Anti-diphtheria (Anti-D)
timeFrame: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)
measure: Concentrations of Antibodies Against Tetanus (Anti-T)
timeFrame: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)
measure: Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT).
timeFrame: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)
measure: Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP).
timeFrame: At Day 90 (1 month post Dose 3 of TETRActHib™ vaccine)
measure: Time to First Malaria Infection
timeFrame: Over the period starting 14 days after Dose 3 of RTS,S/AS02D or Engerix-B® vaccine and extending for 12 weeks thereafter (from Month 2.5 to Month 6)
measure: Number of Subjects Prevalent for Plasmodium Falciparum (P. Falciparum)
timeFrame: At Month 6 (3½ months post Dose 3 of RTS,S/AS02D or Engerix-B® vaccine)
measure: Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia
timeFrame: At Month 6 (3½ months post Dose 3 of RTS,S/AS02D or Engerix-B® vaccine)
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 7 day (Days 0-6) follow-up period after any vaccination with TETRActHib™ vaccine.
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 7 day (Days 0-6) follow-up period after any vaccination with Engerix-B® or RTS,S/AS02D vaccine.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 7 day (Days 0-6) follow-up period after any vaccination with TETRActHib™ vaccine
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 7 day (Days 0-6) follow-up period after any vaccination with Engerix-B® or RTS,S/AS02D vaccine
measure: Number of Subjects With Unsolicited Adverse Events (AEs).
timeFrame: During the 14 day (Days 0-13) follow-up period after any vaccination with of TETRActHib™ vaccine
measure: Number of Subjects With Unsolicited Adverse Events (AEs).
timeFrame: During the 14 day (Days 0-13) follow-up period after vaccination with any among Doses 1 and 2 of Engerix-B® or RTS,S/AS02D vaccine.
measure: Number of Subjects With Unsolicited Adverse Events (AEs).
timeFrame: During the 30 day (Days 0-29) follow-up period after vaccination with Dose 3 of Engerix-B® or RTS,S/AS02D vaccine.
Other outcomes:
Locations:
city: Maputo
country: Mozambique
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Aide P, Aponte JJ, Renom M, Nhampossa T, Sacarlal J, Mandomando I, Bassat Q, Manaca MN, Leach A, Lievens M, Vekemans J, Dubois MC, Loucq C, Ballou WR, Cohen J, Alonso PL. Safety, immunogenicity and duration of protection of the RTS,S/AS02(D) malaria vaccine: one year follow-up of a randomized controlled phase I/IIb trial. PLoS One. 2010 Nov 4;5(11):e13838. doi: 10.1371/journal.pone.0013838.
citation: Aponte JJ, Aide P, Renom M, Mandomando I, Bassat Q, Sacarlal J, Manaca MN, Lafuente S, Barbosa A, Leach A, Lievens M, Vekemans J, Sigauque B, Dubois MC, Demoitie MA, Sillman M, Savarese B, McNeil JG, Macete E, Ballou WR, Cohen J, Alonso PL. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. 2007 Nov 3;370(9598):1543-51. doi: 10.1016/S0140-6736(07)61542-6. Epub 2007 Oct 18.