Clinical trial NCT00436007: Safety and Immunogenicity Study of GSK Biologicals' Malaria Vaccine 257049, When Incorporated Into an EPI Regimen
Official title: Safety and Immunogenicity Study of GSK Biologicals' Investigational Vaccination Regimen Malaria Vaccine 257049, When Incorporated Into an Expanded Program on Immunization (EPI) Regimen That Includes Tritanrix HepB/Hib, OPV, Measles and Yellow Fever Vaccination in Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Africa
Plasmodium falciparum
Malaria
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-02-16
Enrollment: 511
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: This study is being done to assess the possibility of the potential integration of malaria vaccine into the EPI regimen. It will evaluate whether the malaria vaccine is safe and immunogenic in infants aged 6 to 10 weeks at first dose, when co-administered with other EPI vaccine antigens. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed description: Two vaccination schedules will be studied, which constitutes the two alternative three dose regimens for the malaria candidate vaccine 257049 integration into EPI. The co-administered EPI vaccines include GSK Biologicals' Tritanrix™-HepB/Hiberix™, a measles vaccine (depending on the supply availability), Aventis Pasteur's Yellow Fever vaccine Stamaril™ and GSK Biologicals' Oral Polio vaccine Polio Sabin™. Tuberculosis vaccine (Bacillus of Calmette and Guerin, BCG) will be administered according to national medical practice and will not be administered as part of this protocol, but will be documented.

Eligibility criteria: Inclusion Criteria:

* A male or female infant between 6 and 10 weeks of age at the time of first vaccination.
* Signed or thumb-printed informed consent obtained from the parent(s)/guardian(s) of the child. Where parent(s)/guardian(s) are illiterate, the consent form will be countersigned by a witness.
* Subjects who have received one previous dose of OPV and BCG.
* Subjects who are born after a normal gestation period (between 36 and 42 weeks).

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, specifically: ALT and creatinine above acceptable limit; Hemoglobin, Platelet count and Total white cell count below acceptable limit.
* 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.
* OPV administration within four weeks 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 since birth to 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 six months prior to the first vaccine dose.
* Simultaneous participation in any other clinical trial.
* Twins (to avoid misidentification).
* 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: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 to Month 8
Secondary outcomes:
measure: Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
timeFrame: At Months 0, 1, 3 and 7.
measure: Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
timeFrame: At Months 0, 3, 7 and 8.
measure: Concentrations of Antibodies Against Hepatitis B (Anti-HB Antibodies).
timeFrame: At Months 0, 3, 7 and 8.
measure: Concentrations of Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibodies.
timeFrame: At Month 3
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 8 to Month 19
measure: Concentrations of Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibodies.
timeFrame: At Month 3
measure: Titers for Antibodies Against Poliomyelitis Types 1, 2 and 3 (Anti-Polio 1, 2 and 3 Antibodies).
timeFrame: At Month 3
measure: Concentrations of Anti-Bordetella Pertussis Toxin (Anti-BPT) Antibodies.
timeFrame: At Month 3
measure: Concentrations of Anti-measles Antibodies.
timeFrame: At Months 7 and 8.
measure: Titers for Anti-yellow Fever Antibodies.
timeFrame: At Months 7 and 8.
measure: Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
timeFrame: At Months 0, 1, 3 and 7.
measure: Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
timeFrame: At Months 0, 3, 7 and 8.
measure: Concentrations of Anti-circumsporozoite Protein (Anti-CS) Antibodies.
timeFrame: At Months 0, 3, 7 and 8.
measure: Number of Subjects With Solicited Local Symptoms.
timeFrame: During the 7-day (Days 0-6) follow-up period after any vaccination with the Tritanrix™ HepB/Hib, Rouvax™, GSK 257049 and Stamaril™ vaccines.
measure: Number of Subjects With Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) follow-up period after any vaccination
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) follow-up period after any vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 to Month 19
Other outcomes:
Locations:
city: Lambaréné
country: Gabon
facility: GSK Investigational Site
city: Kintampo
country: Ghana
facility: GSK Investigational Site
city: Dar-es-Salaam
country: Tanzania
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Ajua A, Lell B, Agnandji ST, Asante KP, Owusu-Agyei S, Mwangoka G, Mpina M, Salim N, Tanner M, Abdulla S, Vekemans J, Jongert E, Lievens M, Cambron P, Ockenhouse CF, Kremsner PG, Mordmuller B. The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants. Malar J. 2015 Feb 13;14:72. doi: 10.1186/s12936-015-0605-7.
citation: 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.
citation: Asante KP, Abdulla S, Agnandji S, Lyimo J, Vekemans J, Soulanoudjingar S, Owusu R, Shomari M, Leach A, Jongert E, Salim N, Fernandes JF, Dosoo D, Chikawe M, Issifou S, Osei-Kwakye K, Lievens M, Paricek M, Moller T, Apanga S, Mwangoka G, Dubois MC, Madi T, Kwara E, Minja R, Hounkpatin AB, Boahen O, Kayan K, Adjei G, Chandramohan D, Carter T, Vansadia P, Sillman M, Savarese B, Loucq C, Lapierre D, Greenwood B, Cohen J, Kremsner P, Owusu-Agyei S, Tanner M, Lell B. Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial. Lancet Infect Dis. 2011 Oct;11(10):741-9. doi: 10.1016/S1473-3099(11)70100-1. Epub 2011 Jul 22.
citation: Agnandji ST, Asante KP, Lyimo J, Vekemans J, Soulanoudjingar SS, Owusu R, Shomari M, Leach A, Fernandes J, Dosoo D, Chikawe M, Issifou S, Osei-Kwakye K, Lievens M, Paricek M, Apanga S, Mwangoka G, Okissi B, Kwara E, Minja R, Lange J, Boahen O, Kayan K, Adjei G, Chandramohan D, Jongert E, Demoitie MA, Dubois MC, Carter T, Vansadia P, Villafana T, Sillman M, Savarese B, Lapierre D, Ballou WR, Greenwood B, Tanner M, Cohen J, Kremsner PG, Lell B, Owusu-Agyei S, Abdulla S. Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization. J Infect Dis. 2010 Oct 1;202(7):1076-87. doi: 10.1086/656190.