Examine Safety and Immune Responses of GSK 257049 Vaccine When Administered to Infants Living in a Malaria-endemic Region - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00197028

Purpose

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.

Condition	Intervention	Phase
Plasmodium Falciparum Malaria Vaccines Malaria	Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049 Biological: TETRActHib Biological: Engerix-B	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis B Malaria

Drug Information available for: Malaria Vaccines

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From the time of first TETRActHib vaccination until month 6 post Dose 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Number of Subjects Reporting Unsolicited Adverse Events (AEs) Following TETRActHib Vaccination [ Time Frame: over a 14-day follow-up period after Doses 1, 2 and 3 of TETRActHib ] [ Designated as safety issue: No ]
Number of Subjects Reporting Unsolicited Adverse Events (AEs) Following GSK 257049 or Engerix-B Vaccination [ Time Frame: over a 14-day follow-up period after Doses 1 and 2 of GSK 257049 vaccine or Engerix-B; and over a 30-day follow-up period after Dose 3 of GSK 257049 vaccine or Engerix-B ] [ Designated as safety issue: No ]
Number of Subjects Reporting Solicited General and Local Reactions Following TETRActHib Vaccination [ Time Frame: over a 7-day follow-up period (day of vaccination and 6 subsequent days) after TETRActHib ] [ Designated as safety issue: No ]
Number of Subjects Reporting Solicited General and Local Reactions Following GSK 257049 or Engerix-B Vaccination [ Time Frame: over a 7-day follow-up period (day of vaccination and 6 subsequent days) after GSK 257049 vaccine or Engerix-B ] [ Designated as safety issue: No ]
Anti-HBs antibody titers; difference between groups in percent seroprotection [ Time Frame: one month post Dose 3 of GSK 257049 vaccine or Engerix-B ] [ Designated as safety issue: No ]
Anti-hepatitis B (anti-HBs) antibody titers [ Time Frame: prior to vaccination, 1 month post Dose 3 of Engerix B ] [ Designated as safety issue: No ]
Anti-circumsporozoite protein (anti-CS) antibody titers [ Time Frame: prior to vaccination, 1 month post Dose 3, 3½ months post Dose 3 of GSK 257049 vaccine or Engerix B ] [ Designated as safety issue: No ]
Anti-diphtheria antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
Anti-tetanus antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
Anti-pertussis antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
Anti-polyribosyl ribitol phosphate (anti-PRP) antibody titers [ Time Frame: 1 month post Dose 3 of TETRActHib ] [ Designated as safety issue: No ]
first P. falciparum malaria infection [ Time Frame: Starting 14 days after last vaccination with extending for 12 weeks. ] [ Designated as safety issue: No ]
Asexual P. falciparum parasitemia [ Time Frame: At 3½ months post Dose 3 ] [ Designated as safety issue: No ]

Enrollment:	214
Study Start Date:	August 2005
Study Completion Date:	December 2007
Primary Completion Date:	December 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GSK 257049 Group Subjects received 3 doses of TETRActHib vaccine at Days 0, 30 and 60 and 3 doses of GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049 at Days 14, 44 and 74.	Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049 Intramuscular injection into the antero-lateral thigh Biological: TETRActHib Intramuscular injection into the antero-lateral thigh
Active Comparator: Engerix Group Subjects received 3 doses of TETRActHib vaccine on Days 0, 30 and 60 and 3 doses of Engerix vaccine at Days 14, 44 and 74.	Biological: TETRActHib Intramuscular injection into the antero-lateral thigh Biological: Engerix-B Intramuscular injection into the antero-lateral thigh

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

Ages Eligible for Study:	6 Weeks to 12 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00197028

Locations

Mozambique
GSK Investigational Site
Maputo, Mozambique

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

Publications:

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. Epub 2007 Oct 18.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00197028 History of Changes
Other Study ID Numbers:	103967
Study First Received:	September 13, 2005
Last Updated:	July 28, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on February 12, 2012