Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

NCT00380393 | Completed Phase 2 Results

• 1 other identifier: 106464
• Study Type: interventional
• Target: 894
• Locations: 2 countries
• Sites: 2

Brief Summary

This phase IIb trial is being done to find out if the RTS,S/AS01 vaccine helps to prevent children from falling ill with malaria and to evaluate vaccine safety. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Conditions

Malaria

Keywords

Malaria; Plasmodium; RTS; S/AS01; Falciparum

Outcome Measures

Primary Outcomes (1)

• Frequency of First Case of Malaria Meeting the Primary Case Definition

  The first case of malaria meeting the primary case definition was defined as the first or only episodes with the presence of Plasmodium falciparum asexual parasitemia above (\>) 2500 per microliter (μL) and the presence of fever greater than or equal to (≥) 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

  Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Secondary Outcomes (21)

• Frequency of First Case Malaria Meeting the Secondary Case Definition

  Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

• Multiple Events of Malaria Meeting the Primary Case Definition

  Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

• Multiple Events of Malaria Meeting the Secondary Case Definition

  Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

• Number of Subjects Positive for P. Falciparum Parasitaemia

  At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

• Geometric Mean Density of Asexual P. Falciparum Parasite

  At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Study Arms (2)

GSK257049 Group

EXPERIMENTAL

Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.

Biological: GSK malaria vaccine 257049 Vaccine

Rabipur Group

ACTIVE COMPARATOR

Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.

Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine

Interventions

GSK malaria vaccine 257049 Vaccine BIOLOGICAL

3 dose intramuscular injection

Also known as: RTS, S/AS01E vaccine

GSK257049 Group

Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine BIOLOGICAL

3 dose intramuscular injection

Rabipur Group

Eligibility Criteria

• Age: 5 Months - 17 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• A male or female child of between 5 months and 17 months 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.

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 for haemoglobin, total white cell count, platelets, ALT and creatinine out of acceptable limits.
• Planned administration/administration of a vaccine not foreseen by the study within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid or scheduled diphtheria, pertussis or measles vaccine.
• 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 (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Kilifi, 80108, Kenya

Location

GSK Investigational Site

Amani, Tanga, Tanzania

Location

Related Publications (7)

• Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitie MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med. 2008 Dec 11;359(24):2521-32. doi: 10.1056/NEJMoa0807381. Epub 2008 Dec 8.

  PMID: 19064627 BACKGROUND

• Lang TA, Gould J, von Seidlein L, Lusingu JP, Mshamu S, Ismael S, Liheluka E, Kamuya D, Mwachiro D, Olotu A, Njuguna P, Bejon P, Marsh V, Molyneux C. Approaching the community about screening children for a multicentre malaria vaccine trial. Int Health. 2012 Mar;4(1):47-54. doi: 10.1016/j.inhe.2011.10.003.

  PMID: 24030880 BACKGROUND

• Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Olivier A, Benns S, Olomi R, Msham S, Lang T, Gould J, Hallez K, Guerra Y, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Dekker D, Malle L, Ismael S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, Bejon P, von Seidlein L. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. PLoS One. 2010 Nov 29;5(11):e14090. doi: 10.1371/journal.pone.0014090.

  PMID: 21124768 BACKGROUND

• Olotu A, Lusingu J, Leach A, Lievens M, Vekemans J, Msham S, Lang T, Gould J, Dubois MC, Jongert E, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Lapierre D, Ballou WR, Cohen J, Lemnge MM, Peshu N, Marsh K, Riley EM, von Seidlein L, Bejon P. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 2011 Feb;11(2):102-9. doi: 10.1016/S1473-3099(10)70262-0. Epub 2011 Jan 13.

  PMID: 21237715 BACKGROUND

• Olotu A, Clement F, Jongert E, Vekemans J, Njuguna P, Ndungu FM, Marsh K, Leroux-Roels G, Bejon P. Avidity of anti-circumsporozoite antibodies following vaccination with RTS,S/AS01E in young children. PLoS One. 2014 Dec 15;9(12):e115126. doi: 10.1371/journal.pone.0115126. eCollection 2014.

  PMID: 25506706 DERIVED

• Warimwe GM, Fletcher HA, Olotu A, Agnandji ST, Hill AV, Marsh K, Bejon P. Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data. BMC Med. 2013 Aug 21;11:184. doi: 10.1186/1741-7015-11-184.

  PMID: 23962071 DERIVED

• Horowitz A, Hafalla JC, King E, Lusingu J, Dekker D, Leach A, Moris P, Cohen J, Vekemans J, Villafana T, Corran PH, Bejon P, Drakeley CJ, von Seidlein L, Riley EM. Antigen-specific IL-2 secretion correlates with NK cell responses after immunization of Tanzanian children with the RTS,S/AS01 malaria vaccine. J Immunol. 2012 May 15;188(10):5054-62. doi: 10.4049/jimmunol.1102710. Epub 2012 Apr 13.

  PMID: 22504653 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

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; 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: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2006
• First Posted: September 26, 2006
• Study Start: January 3, 2007
• Primary Completion: August 15, 2008
• Study Completion: November 11, 2008
• Last Updated: July 3, 2018
• Results First Posted: July 3, 2018

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

KE (1); TA (1)