Clinical trial NCT00289185: Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants
Official title: A Phase IIb Randomized, Double-blind, Controlled Study of the Safety, Immunogenicity and Proof-of-concept of RTS,S/AS02D, 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Malaria Vaccines
Keywords: Coccidiosis
Parasitic Diseases
Malaria, Falciparum
Malaria
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-02-09
Enrollment: 340
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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.

Primary outcomes:
measure: Concentrations of Antibodies Against Hepatitis B (Anti-HB)
timeFrame: Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Week 0 to Month 9.
measure: Concentrations of Antibodies Against Diphtheria (Anti-D)
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Concentrations of Antibodies Against Tetanus (Anti-T)
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP).
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Month 9 to Month 20.
measure: Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT).
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Number of Subjects With Hepatitis B Antibody (Anti-HB) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
timeFrame: Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.
measure: Number of Subjects With Anti-diphtheria Antibody (Anti-D) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Number of Subjects With Anti-tetanus Antibody (Anti-T) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Number of Subjects With Anti-polyribosyl Ribitol Phosphate Antibody (Anti-PRP) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
measure: Number of Subjects With Anti-Bordetella Pertussis Toxin Antibody (Anti-BPT) Concentrations Equal to or Above (>=) the Seropositivity Cut-off Value
timeFrame: Prior to vaccination at Week 0 (PRE), and at Month 3.
Secondary outcomes:
measure: Concentrations of Anti-Circumsporozoite Protein (Anti-CS) Antibodies
timeFrame: Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: Within 7 days (Days 0-6) after vaccination with the RTS,S/AS02D or Engerix-B vaccine.
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Unsolicited Adverse Events (AEs).
timeFrame: Within 30 days (Days 0-29) after vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study, from Week 0 to Month 20.
measure: Time to First Malaria Infection
timeFrame: Over the period starting 14 days after Dose 3 of RTS,S or HBV vaccine and extending for 6 months thereafter (from Month 2.5 up to Month 9).
measure: Number of Subjects Prevalent for Parasitemia
timeFrame: At Month 9
measure: Plasmodium Falciparum (P. Falciparum) Parasite Density in Subjects Prevalent for Parasitemia
timeFrame: At Month 9
Other outcomes:
Locations:
city: Dar-es-Salaam
country: Tanzania
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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, Demoitie 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. doi: 10.1056/NEJMoa0807773. Epub 2008 Dec 8.
citation: 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.