Long-Term Follow-up of Children for a 2-Year Period to Confirm the Safety and Immunogenicity of GSK 257049 Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00323622
First received: September 8, 2005
Last updated: February 27, 2014
Last verified: December 2013
  Purpose

The RTS,S/AS02A vaccine (or GSK 257049 vaccine), GSK Biologicals' candidate Plasmodium falciparum (P. falciparum) malaria vaccine is being developed 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 P. falciparum. The vaccine would also provide protection against infection with hepatitis B virus (HBV).

This phase IIb trial is being carried out following the demonstration of efficacy of the candidate malaria 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 this study, the children from Mozambique (NCT= NCT00197041) are followed-up to assess the safety, immunogenicity and efficacy of the candidate malaria vaccine for a two year period commencing 21 months after Dose 1.

This protocol posting deals with objectives & outcome measures of the extension phase at year 2. During this extension study, no new subjects will be recruited and no vaccine will be administered.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Malaria
Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
Biological: Engerix™-B
Biological: Hiberix®
Biological: Prevnar™
Drug: sulfadoxine-pyrimethamine
Drug: amodiaquine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: An Open Study for a 2-year Period to Confirm the Safety and Immunogenicity of the Candidate Malaria Vaccine RTS,S/AS02A in Mozambican Children Aged 1 to 4 Years at the Time of First Vaccine Dose.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period: from Month 21 to Month 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study). ] [ Designated as safety issue: No ]
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.


Secondary Outcome Measures:
  • Anti-circumsporozoite Protein (CS) Antibody Concentrations. [ Time Frame: At Months 33 and 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study). ] [ Designated as safety issue: No ]
    Concentrations for anti-CS antibodies are presented as Geometric Mean Concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off of 0.5 EL.U/mL. Subjects were pooled across age ranges for this outcome measure.

  • Anti-hepatitis B (HBs) Antibody Concentrations. [ Time Frame: At Months 33 and 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study). ] [ Designated as safety issue: No ]
    Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). Anti-HBs antibody concentration levels were measured in blood samples from Cohort 2 only.

  • Time to First or Only Clinical Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Primary Case Definition [ Time Frame: From Month 21 to Month 33 (M21-33), and from Month 33 to Month 45 (M33-45). Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in study NCT00197041 ] [ Designated as safety issue: No ]
    Malaria infection by Plasmodium falciparum was detected by passive case detection. A symptomatic PFMI episode of Primary Case Definition (PCD) was defined as the presence of P. falciparum asexual parasitaemia above 2500 per µL on Giemsa stained thick blood films accompanied by fever (axillary temperature equal or above 37.5 degrees Celsius at the time of presentation) occurring in an unwell child brought for treatment to a healthcare facility. The time to first or only episode of symptomatic PFMI is expressed in terms of rate of first PFMI (RPFMI), that is, the number of PFMI events reported (n) over the period elapsed until the PFMI event occurred (i.e. events per Persons Year at Risk [PYAR]) for each group. Analysis for this outcome was solely performed on Cohort 1 subjects, with groups pooled across age ranges.

  • Time to First or Only Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Secondary Case Definition 1 [ Time Frame: From Month 21 to Month 33 (M21-33), and from Month 33 to Month 45 (M33-45). Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in study NCT00197041 ] [ Designated as safety issue: No ]
    PFMI was detected by passive case detection. Symptomatic PFMI of Secondary Case Definition (SCD) 1 was defined as the presence of P. falciparum asexual parasitaemia (any level if parasitemia) on Giemsa stained thick blood films accompanied by fever (axillary temperature equal or above 37.5 degrees Celsius) in an unwell child brought for treatment. The time to first or only episode of symptomatic PFMI is expressed in terms of rate of first PFMI (RPFMI), that is, the number of PFMI events reported (n) over the period elapsed until the PFMI event occurred (i.e. events per Persons Year at Risk [PYAR]) for each group. Analysis for this outcome was solely performed on Cohort 1 subjects, with groups pooled across age ranges.

  • Time to First or Only Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Secondary Case Definition 2 [ Time Frame: From Month 21 to Month 33 (M21-33), and from Month 33 to Month 45 (M33-45). Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in study NCT00197041 ] [ Designated as safety issue: No ]
    PFMI was detected by passive case detection. Symptomatic PFMI of Secondary Case Definition (SCD) 2 was defined as the presence of P. falciparum asexual parasitaemia (any level if parasitemia) on Giemsa stained thick blood films in an unwell child brought for treatment with a history of fever (axillary temperature equal or above 37.5 degrees Celsius) within 24 hours or documented fever. The time to first or only episode of symptomatic PFMI is expressed in terms of rate of first PFMI (RPFMI), that is, the number of PFMI events reported (n) over the period elapsed until the PFMI event occurred (i.e. events per Persons Year at Risk [PYAR]) for each group. Analysis for this outcome was performed on Cohort 1 subjects, with groups pooled across age ranges.

  • Time to First or Only Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Secondary Case Definition 3 [ Time Frame: From Month 21 to Month 33 (M21-33), and from Month 33 to Month 45 (M33-45). Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in study NCT00197041 ] [ Designated as safety issue: No ]
    PFMI was detected by passive case detection. Symptomatic PFMI of Secondary Case Definition (SCD) 3 was defined as the presence of P. falciparum asexual parasitaemia above 15000 per microliter (µL) on Giemsa stained thick blood films accompanied by fever (axillary temperature equal or above 37.5 degrees Celsius) in an unwell child brought for treatment to a healthcare facility. The time to first or only episode of symptomatic PFMI is expressed in terms of rate of first PFMI (RPFMI), that is, the number of PFMI events reported (n) over the period elapsed until the PFMI event occurred (i.e. events per Persons Year at Risk [PYAR]) for each group. Analysis for this outcome was performed on Cohort 1 subjects solely, with groups pooled across age ranges.

  • Number of Subjects With Anemia. [ Time Frame: At Months 33 and 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study). ] [ Designated as safety issue: No ]
    Anemia was indicated by a hematocrit level (HL) below (<) 25%. The numbers of subjects with HL below (<) and above or equal (≥) 25 %, and with missing HL results were tabulated. In the tabulation below, the number of subjects falling into the "HL ≥25%" category corresponds to the number of subjects with anemia as asked per outcome. Analysis for this outcome was performed on Cohort 1 subjects solely, with groups pooled across age ranges.

  • Number of Primary Case Definition Clinical Episodes of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) [ Time Frame: From Month 21 to Month 33 (M21-33), and from Month 33 to Month 45 (M33-45). Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in study NCT00197041 ] [ Designated as safety issue: No ]
    PFMI was detected by passive case detection. A symptomatic PFMI episode of Primary Case Definition (PCD) was defined as the presence of P. falciparum asexual parasitaemia above 2500 per µL on Giemsa stained thick blood films accompanied by fever (axillary temperature equal or above 37.5 degrees Celsius at the time of presentation) occurring in an unwell child brought for treatment to a healthcare facility. The number of PFMI episodes (EPFMI) per person-year (pyr) was tabulated, using as unit EPFMI episode per pyr. Analysis for this outcome was performed on Cohort 1 subjects solely, with groups pooled across age ranges.

  • Number of Subjects Prevalent for Plasmodium Falciparum (P. Falciparum) Parasitemia [ Time Frame: At Months 33 (M33) and 45 (M45) (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study). ] [ Designated as safety issue: No ]
    Subjects prevalent for P. falciparum parasitemia were defined as subjects with the presence of P. falciparum asexual parasitemia above 0 per microliter (µL) on Giemsa stained thick blood films.Analysis for this outcome was performed on Cohort 1 subjects solely, with groups pooled across age ranges.


Enrollment: 1737
Study Start Date: April 2005
Study Completion Date: May 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1-RTS,S/AS02A <24M Group
Subjects, male and female, aged 12 to 24 months at first vaccination, were administered 3 doses of RTS,S/AS02A (GSK 257049) vaccine at Months 0, 1 and 2 in the NCT00197041 Study. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study. Subjects in this group are part of the Cohort 1 of the study, which was followed for analysis of malaria infection.
Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
IM injection in the deltoid muscle
Other Names:
  • RTS
  • S/AS02A vaccine
Experimental: Cohort 1-RTS,S/AS02A ≥24M Group
Subjects, male and female, aged between 24 and 48 months at first vaccination, were administered 3 doses of RTS,S/AS02A (GSK 257049) vaccine at Months 0, 1 and 2 in the NCT00197041 Study. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study. Subjects in this group are part of the Cohort 1 of the study, which was followed for analysis of malaria infection.
Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
IM injection in the deltoid muscle
Other Names:
  • RTS
  • S/AS02A vaccine
Experimental: Cohort 2-RTS,S/AS02A <24M Group
Subjects, male and female, aged 12 to 24 months at first vaccination, were administered 3 doses of RTS,S/AS02A (GSK 257049) vaccine at Months 0, 1 and 2 in the NCT00197041 Study. Subjects in this group are part of the Cohort 2 of the study, which was followed for analysis of malaria disease. As Cohort 2 subjects, subjects in this group also received as part of the Primary NCT00197041 Study one dose of sulfadoxine-pyrimethamine and amodiaquine per day for 3 days 4 weeks prior to onset of surveillance, so as to clear any parasitemia. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study.
Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
IM injection in the deltoid muscle
Other Names:
  • RTS
  • S/AS02A vaccine
Drug: sulfadoxine-pyrimethamine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Drug: amodiaquine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Experimental: Cohort 2-RTS,S/AS02A ≥24M Group
Subjects, male and female, aged between 24 and 48 months at first vaccination, were administered 3 doses of RTS,S/AS02A (GSK 257049) vaccine at Months 0, 1 and 2 of the NCT00197041 Study. Subjects in this group are part of the Cohort 2 of the study, which was followed for analysis of malaria disease. As Cohort 2 subjects, subjects in this group also received as part of the Primary NCT00197041 Study one dose of sulfadoxine-pyrimethamine and amodiaquine per day for 3 days 4 weeks prior to onset of surveillance, so as to clear any parasitemia. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study.
Biological: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049
IM injection in the deltoid muscle
Other Names:
  • RTS
  • S/AS02A vaccine
Drug: sulfadoxine-pyrimethamine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Drug: amodiaquine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Active Comparator: Cohort 1-Prevnar-Hiberix <24M Group
Subjects, male and female, aged 12 to 24 months at first vaccination, were administered 2 doses of Prevnar™ vaccine at Months 0 and 2 and 1 dose of Hiberix® vaccine at Month 1 in the Primary NCT00197041 Study. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study. Subjects in this group are part of the Cohort 1 of the study, which was followed for analysis of malaria infection.
Biological: Hiberix®
IM injection in the deltoid muscle
Biological: Prevnar™
IM injection in the deltoid muscle
Active Comparator: Cohort 1-Engerix-B ≥24M Group
Subjects, male and female, aged between 24 and 48 months at first vaccination, were administered 3 doses of Engerix®-B vaccine at Months 0, 1 and 2 in the Primary NCT00197041 Study. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study. Subjects in this group are part of the Cohort 1 of the study, which was followed for analysis of malaria infection.
Biological: Engerix™-B
IM injection in the deltoid muscle
Active Comparator: Cohort 2-Prevnar- Hiberix <24M Group
Subjects, male and female, aged 12 to 24 months at first vaccination, were administered 2 doses of Prevnar™ vaccine at Months 0 and 2 and 1 dose of Hiberix® vaccine at Month 1 in the Primary NCT00197041 Study. Subjects in this group are part of the Cohort 2 of the study, which was followed for analysis of malaria disease. As Cohort 2 subjects, subjects in this group also received as part of the Primary NCT00197041 Study one dose of sulfadoxine-pyrimethamine and amodiaquine per day for 3 days 4 weeks prior to onset of surveillance, so as to clear any parasitemia. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study.
Biological: Hiberix®
IM injection in the deltoid muscle
Biological: Prevnar™
IM injection in the deltoid muscle
Drug: sulfadoxine-pyrimethamine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Drug: amodiaquine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Active Comparator: Cohort 2-Engerix-B ≥24M Group
Subjects, male and female, aged between 24 and 48 months at first vaccination, were administered 3 doses of Engerix®-B vaccine at Months 0, 1 and 2 in the Primary NCT00197041 Study. Subjects in this group are part of the Cohort 2 of the study, which was followed for analysis of malaria disease. As Cohort 2 subjects, subjects in this group also received as part of the Primary NCT00197041 Study one dose of sulfadoxine-pyrimethamine and amodiaquine per day for 3 days 4 weeks prior to onset of surveillance, so as to clear any parasitemia. No additional dose of vaccine or drug was administered during this open follow-up NCT00323622 study.
Biological: Engerix™-B
IM injection in the deltoid muscle
Drug: sulfadoxine-pyrimethamine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance
Drug: amodiaquine
1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance

  Eligibility

Ages Eligible for Study:   33 Months to 69 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Completion of Visit 7, Month 21 of 104297 (NCT= NCT00197041).
  • Written informed consent obtained from the parent(s) or guardian(s) of the subject

Exclusion criteria:

  • Planned use of any investigational or non-registered drug or vaccine during the study period.
  • Simultaneous participation in any other clinical trial
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00323622

Locations
Mozambique
GSK Investigational Site
Maputo, Mozambique
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00323622     History of Changes
Other Study ID Numbers: 104297
Study First Received: September 8, 2005
Results First Received: March 29, 2013
Last Updated: February 27, 2014
Health Authority: South Africa: Medicines Control Council
United States: Food and Drug Administration

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Amodiaquine
Pyrimethamine
Sulfadoxine
Sulfadoxine-pyrimethamine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on April 17, 2014