Study of Safety, Immunogenicity and Efficacy of a Candidate Malaria Vaccine in Tanzanian Infants

NCT00289185 | Completed Phase 2 Results

• 2 other identifiers: 1042982015-001539-19
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria; Malaria Vaccines

Keywords

Coccidiosis; Parasitic Diseases; Malaria, Falciparum; Malaria

Outcome Measures

Primary Outcomes (12)

• Concentrations of Antibodies Against Hepatitis B (Anti-HB)

  Concentrations were expressed as geometric mean concentrations (GMCs) in milli-international unit per milliliter (mIU/mL). The cut-off of the assay was the seroprotection cut-off of 10 mIU/mL. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.

• Number of Subjects With Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From Week 0 to Month 9.

• Concentrations of Antibodies Against Diphtheria (Anti-D)

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Concentrations of Antibodies Against Tetanus (Anti-T)

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off of 0.1 IU/mL. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Concentrations of Anti-polyribosyl Ribitol Phosphate Antibodies (Anti-PRP).

  Concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The cut-off of the assay is the seroprotection cut-off value of 0.15 µg/mL. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Number of Subjects With Serious Adverse Events (SAEs)

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

  From Month 9 to Month 20.

• Concentrations of Anti-Bordetella Pertussis Toxin Antibodies (Anti-BPT).

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA unit per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off of 15 EL.U/mL. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Number of Subjects With Hepatitis B Antibody (Anti-HB) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value

  The seroprotection cut-off value was 10 milli-international units per milliliter (mIU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), at Month 2 and at Month 3.

• Number of Subjects With Anti-diphtheria Antibody (Anti-D) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Number of Subjects With Anti-tetanus Antibody (Anti-T) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.1 international unit per milliliter (IU/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Number of Subjects With Anti-polyribosyl Ribitol Phosphate Antibody (Anti-PRP) Concentrations Equal to or Above (>=) the Seroprotection Cut-off Value

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seroprotection cut-off value was 0.15 microgram per milliliter (µg/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

• Number of Subjects With Anti-Bordetella Pertussis Toxin Antibody (Anti-BPT) Concentrations Equal to or Above (>=) the Seropositivity Cut-off Value

  Antibodies were measured by Enzyme-linked immunosorbent assay (ELISA). The seropositivity cut-off value was 15 ELISA units per milliliter (EL.U/mL). Blood samples were collected prior to vaccination at Week 0 (PRE), and at Month 3. Month 3 results are the specific results for this primary outcome measure.

  Prior to vaccination at Week 0 (PRE), and at Month 3.

Secondary Outcomes (9)

• Concentrations of Anti-Circumsporozoite Protein (Anti-CS) Antibodies

  Prior to vaccination at Week 0 (PRE), at Month 2, at Month 3 and at Month 9.

• Number of Subjects With Solicited Local Symptoms.

  Within 7 days (Days 0-6) after vaccination with the RTS,S/AS02D or Engerix-B vaccine.

• Number of Subjects With Solicited Local Symptoms.

  Within 7 days (Days 0-6) after vaccination with the TETRActHib vaccine.

• Number of Subjects With Solicited General Symptoms.

  Within 7 days (Days 0-6) after vaccination

• Number of Subjects With Unsolicited Adverse Events (AEs).

  Within 30 days (Days 0-29) after vaccination

Study Arms (2)

RTS,S/AS02D Group

EXPERIMENTAL

Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of the RTS,S/AS02D vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The RTS,S/AS02D vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh.

Biological: RTS,S/AS02D; Biological: TETRActHib™

Engerix-B Group

ACTIVE COMPARATOR

Subjects aged between 6 and 10 weeks at the time of first vaccination received by intramuscular injection a 3-dose vaccination course of Engerix-B® vaccine co-administered with the TETRActHib™ vaccine at Week 0, Week 4 (Month 1) and Week 8 (Month 2). The Engerix-B® vaccine was administered in the left anterolateral thigh, and the TETRActHib™ vaccine in the right anterolateral thigh..

Biological: Engerix-B®; Biological: TETRActHib™

Interventions

RTS,S/AS02D BIOLOGICAL

3-dose intramuscular injection in the thigh

Also known as: GSK 257146, RTS, S/AS02D

RTS,S/AS02D Group

Engerix-B® BIOLOGICAL

3-dose intramuscular injection in the thigh.

Engerix-B Group

TETRActHib™ BIOLOGICAL

3-dose intramuscular injection in the thigh.

Also known as: DTPw/Hib

Engerix-B Group; RTS,S/AS02D Group

Eligibility Criteria

• Age: 6 Weeks - 10 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Dar es Salaam, Tanzania

Location

Related Publications (2)

• 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.

  PMID: 19064623 BACKGROUND

• 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.

  PMID: 23297680 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; Coccidiosis; Parasitic Diseases; Malaria, Falciparum

Interventions

RTS malaria vaccine; Engerix-B

Condition Hierarchy (Ancestors)

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

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: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2006
• First Posted: February 9, 2006
• Study Start: September 27, 2006
• Primary Completion: February 11, 2008
• Study Completion: January 15, 2009
• Last Updated: October 29, 2020
• Results First Posted: July 8, 2013

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

TA (1)