Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants - Full Text View

Purpose

GSK Biologicals in partnership with the Malaria Vaccine Initiative at PATH is developing a candidate malaria vaccine GSK 257049 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).

In order to integrate the malaria vaccine into the EPI regimen in malaria-endemic regions, a new variant RTS,S/AS02D (0.5 mL dose) 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	Biological: Engerix-B Biological: TETRActHib Biological: GSK Malaria vaccine 257049 vaccine	Phase 2

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:	Safety, Immunogenicity & Proof-of-concept Study of GSK 257146, a Candidate Malaria Vaccine, When Incorporated Into an Expanded Program on Immunization (EPI) Regimen That Includes DTPw/Hib in Infants Living in a Malaria-endemic Region

Resource links provided by NLM:

MedlinePlus related topics: Diphtheria Hepatitis Hepatitis B Malaria Parasitic Diseases Tetanus Whooping Cough

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Occurrence of SAEs [ Time Frame: From the time of first vaccination until seven months post Dose 3 (Month 9). ] [ Designated as safety issue: Yes ]
Anti-Hepatitis B surface agent (HBs) antibody titers: difference between groups in percent seroprotection. [ Time Frame: One month post Dose 3 ] [ Designated as safety issue: No ]
Anti-diphtheria antibody titers: difference between groups in percent seroprotection [ Time Frame: One month post Dose 3. ] [ Designated as safety issue: No ]
Anti-tetanus antibody titers: difference between groups in percent seroprotection [ Time Frame: One month post Dose 3. ] [ Designated as safety issue: No ]
Anti- polyribosyl-ribitol-phosphate (anti-PRP) antibody titers: difference between groups in percent seroprotection. [ Time Frame: One month post Dose 3. ] [ Designated as safety issue: No ]
Anti-pertussis antibody titers: GMT ratio between groups [ Time Frame: One month post Dose 3. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence of unsolicited AEs. [ Time Frame: After Dose 1, 2 and 3 of vaccine over a 30-day follow-up period ] [ Designated as safety issue: Yes ]
Occurrence of solicited general and local reactions. [ Time Frame: Over a 7-day follow-up period after each vaccination ] [ Designated as safety issue: Yes ]
Anti HBs antibody titers. [ Time Frame: Prior to vaccination, one month post Dose 2 and one month post Dose 3 ] [ Designated as safety issue: No ]
Anti-tetanus antibody titers measured by ELISA [ Time Frame: At screening and one month post Dose 3. ] [ Designated as safety issue: No ]
Anti-pertussis antibody titers measured by ELISA [ Time Frame: At screening and one month post Dose 3. ] [ Designated as safety issue: No ]
Anti-PRP antibody titers measured by ELISA. [ Time Frame: At screening and one month post Dose 3. ] [ Designated as safety issue: No ]
First malaria infection (first recording of infection of asexual stage falciparum parasites detected by the active detection of infection surveillance). [ Time Frame: Over a period starting 14 days after Dose 3 and extending for 6 months ] [ Designated as safety issue: No ]
The asexual P. falciparum parasitemia (prevalence and density). [ Time Frame: At 7 months post Dose 3 (Month 9). ] [ Designated as safety issue: No ]
Antibody titers to the P. falciparum circumsporozoite (CS) repeat [ Time Frame: Prior to vaccination, one month post Dose 2, one month post Dose 3 and 7 months post Dose 3 ] [ Designated as safety issue: No ]
Anti-diphtheria antibody titers measured by ELISA. [ Time Frame: At screening and one month post Dose 3. ] [ Designated as safety issue: No ]

Enrollment:	340
Study Start Date:	September 2006
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Group B	Biological: Engerix-B 3-dose intramuscular injection Biological: TETRActHib 3-dose intramuscular injection.
Experimental: Group A	Biological: TETRActHib 3-dose intramuscular injection. Biological: GSK Malaria vaccine 257049 vaccine 3-dose intramuscular injection. Other Name: RTS,S/AS02D

Detailed Description:

This is a phase 2b trial designed to evaluate the safety and immunogenicity of RTS,S/AS02D when co-administered with a multivalent DTPw/Hib (Aventis Pasteur's TETRActHib vaccine). Infants randomized to the control group will receive a licensed hepatitis B vaccine, Engerix-B in place of RTS,S/AS02D.

Data pertaining to RTS,S/AS02D or Engerix-B will be collected in a double blinded manner; data relating to TETRActHib will be collected in an open fashion.

Oral polio vaccine (OPV) will be administered at birth, 8, 12, 16 weeks in co-administration with other vaccines and will not be administered as part of this protocol. Antibody titers to OPV will not be assessed as part of this protocol.

Eligibility

Ages Eligible for Study:	6 Weeks to 10 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion criteria:

A male or female infant between 6 and 10 weeks of age at the time of first vaccination.
Written or oral, signed or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits).
Born to a mother who is HBsAg negative & HIV negative.
Born after a normal gestation period (between 36 and 42 weeks).
Subjects who live within a 5 km radius of a dispensary.

Exclusion criteria:

Acute disease at the time of enrolment.
Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.
Laboratory screening tests out of range for haemoglobin, total white cell count, platelets, ALT and creatinine.
Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b or hepatitis B vaccines.
BCG administration within one week of proposed administration of a study vaccine.
Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine(s).
Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Previous participation in any other malaria vaccine trial.
Simultaneous participation in any other clinical trial.
Same sex twin.
Maternal death.
History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00289185

Locations

Tanzania
GSK Investigational Site
Dar-es-Salaam, Tanzania

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

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

Abdulla S, Salim N, Machera F, Kamata R, Juma O, Shomari M, Kubhoja S, Mohammed A, Mwangoka G, Aebi T, Mshinda H, Schellenberg D, Carter T, Villafana T, Dubois MC, Leach A, Lievens M, Vekemans J, Cohen J, Ballou WR, Tanner M. Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02(D) malaria vaccine in infants living in a malaria-endemic region. Malar J. 2013 Jan 8;12:11. doi: 10.1186/1475-2875-12-11.

Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, Membi C, Omari S, Urassa A, Mshinda H, Jumanne A, Salim N, Shomari M, Aebi T, Schellenberg DM, Carter T, Villafana T, Demoitié MA, Dubois MC, Leach A, Lievens M, Vekemans J, Cohen J, Ballou WR, Tanner M. Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med. 2008 Dec 11;359(24):2533-44. Epub 2008 Dec 8.

Responsible Party:	Study Director, GSK
ClinicalTrials.gov Identifier:	NCT00289185 History of Changes
Other Study ID Numbers:	104298
Study First Received:	February 8, 2006
Last Updated:	September 3, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:

Malaria
Coccidiosis
Malaria, Falciparum
Parasitic Diseases

Additional relevant MeSH terms:

Malaria
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on May 21, 2013