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

NCT00323622 | Completed Phase 2 Results

• 1 other identifier: 104297
• Study Type: interventional
• Target: 1,737
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Serious Adverse Events (SAEs)

  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.

  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).

Secondary Outcomes (9)

• Anti-circumsporozoite Protein (CS) Antibody Concentrations.

  At Months 33 and 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study).

• Anti-hepatitis B (HBs) Antibody Concentrations.

  At Months 33 and 45 (Month 0 = administration of Dose 1 of RTS,S/AS02A or comparator vaccine in the NCT00197041 study).

• Time to First or Only Clinical Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Primary Case Definition

  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

• Time to First or Only Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Secondary Case Definition 1

  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

• Time to First or Only Episode of Symptomatic Plasmodium Falciparum Malaria Infection (PFMI) of Secondary Case Definition 2

  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

Study Arms (8)

Cohort 1-RTS,S/AS02A <24M Group

EXPERIMENTAL

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

Cohort 1-RTS,S/AS02A ≥24M Group

EXPERIMENTAL

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

Cohort 2-RTS,S/AS02A <24M Group

EXPERIMENTAL

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; Drug: sulfadoxine-pyrimethamine; Drug: amodiaquine

Cohort 2-RTS,S/AS02A ≥24M Group

EXPERIMENTAL

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; Drug: sulfadoxine-pyrimethamine; Drug: amodiaquine

Cohort 1-Prevnar-Hiberix <24M Group

ACTIVE COMPARATOR

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®; Biological: Prevnar™

Cohort 1-Engerix-B ≥24M Group

ACTIVE COMPARATOR

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

Cohort 2-Prevnar- Hiberix <24M Group

ACTIVE COMPARATOR

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®; Biological: Prevnar™; Drug: sulfadoxine-pyrimethamine; Drug: amodiaquine

Cohort 2-Engerix-B ≥24M Group

ACTIVE COMPARATOR

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; Drug: sulfadoxine-pyrimethamine; Drug: amodiaquine

Interventions

GSK Biologicals' candidate Plasmodium falciparum malaria vaccine 257049 BIOLOGICAL

IM injection in the deltoid muscle

Also known as: RTS, S/AS02A vaccine

Cohort 1-RTS,S/AS02A <24M Group; Cohort 1-RTS,S/AS02A ≥24M Group; Cohort 2-RTS,S/AS02A <24M Group; Cohort 2-RTS,S/AS02A ≥24M Group

Engerix™-B BIOLOGICAL

IM injection in the deltoid muscle

Cohort 1-Engerix-B ≥24M Group; Cohort 2-Engerix-B ≥24M Group

Hiberix® BIOLOGICAL

IM injection in the deltoid muscle

Cohort 1-Prevnar-Hiberix <24M Group; Cohort 2-Prevnar- Hiberix <24M Group

Prevnar™ BIOLOGICAL

IM injection in the deltoid muscle

Cohort 1-Prevnar-Hiberix <24M Group; Cohort 2-Prevnar- Hiberix <24M Group

sulfadoxine-pyrimethamine DRUG

1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance

Cohort 2-Engerix-B ≥24M Group; Cohort 2-Prevnar- Hiberix <24M Group; Cohort 2-RTS,S/AS02A <24M Group; Cohort 2-RTS,S/AS02A ≥24M Group

amodiaquine DRUG

1 dose orally per day for 3 days, 4 weeks prior to onset of surveillance

Cohort 2-Engerix-B ≥24M Group; Cohort 2-Prevnar- Hiberix <24M Group; Cohort 2-RTS,S/AS02A <24M Group; Cohort 2-RTS,S/AS02A ≥24M Group

Eligibility Criteria

• Age: 33 Months - 69 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Planned use of any investigational or non-registered drug or vaccine during the study period.
• Simultaneous participation in any other clinical trial

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Maputo, Mozambique

Location

Related Publications (4)

• Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Aide P, Sigauque B, Milman J, Mandomando I, Bassat Q, Guinovart C, Espasa M, Corachan S, Lievens M, Navia MM, Dubois MC, Menendez C, Dubovsky F, Cohen J, Thompson R, Ballou WR. Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow-up of a randomised controlled trial. Lancet. 2005 Dec 10;366(9502):2012-8. doi: 10.1016/S0140-6736(05)67669-6.

  PMID: 16338450 BACKGROUND

• Aponte et al. A 4 years follow-up of the safety, immunogenicity and efficacy of the candidate malaria vaccine RTS,S/AS02A in children vaccinated at aged 1 to 4 years in a malaria-endemic region of Mozambique. Abstract presented at the 56th Annual Meeting ASTMH, Philadelphia, PA, USA, 05-07 November 2007.

  BACKGROUND

• Sacarlal J, Aide P, Aponte JJ, Renom M, Leach A, Mandomando I, Lievens M, Bassat Q, Lafuente S, Macete E, Vekemans J, Guinovart C, Sigauque B, Sillman M, Milman J, Dubois MC, Demoitie MA, Thonnard J, Menendez C, Ballou WR, Cohen J, Alonso PL. Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children. J Infect Dis. 2009 Aug 1;200(3):329-36. doi: 10.1086/600119.

  PMID: 19569964 BACKGROUND

• Aide P, Dobano C, Sacarlal J, Aponte JJ, Mandomando I, Guinovart C, Bassat Q, Renom M, Puyol L, Macete E, Herreros E, Leach A, Dubois MC, Demoitie MA, Lievens M, Vekemans J, Loucq C, Ballou WR, Cohen J, Alonso PL. Four year immunogenicity of the RTS,S/AS02(A) malaria vaccine in Mozambican children during a phase IIb trial. Vaccine. 2011 Aug 11;29(35):6059-67. doi: 10.1016/j.vaccine.2011.03.041. Epub 2011 Apr 7.

  PMID: 21443960 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Malaria

Interventions

RTS,S-AS02A vaccine; Hiberix; Heptavalent Pneumococcal Conjugate Vaccine; fanasil, pyrimethamine drug combination; Amodiaquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Pneumococcal Vaccines; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: May 9, 2006
• Study Start: April 1, 2005
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: December 9, 2016
• Results First Posted: March 27, 2014

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

MO (1)