Clinical trial NCT01345240: Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
Official title: Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Malaria Vaccines
Keywords: Africa
Plasmodium falciparum
Malaria vaccine
hepatitis B
EPI
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-05-02
Enrollment: 705
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study has been designed to support the indication of the candidate vaccine (also referred to as GSK 257049 or RTS,S in this record) against hepatitis B virus infection, when administered as a primary vaccination integrated into an Expanded Program on Immunization (EPI) regimen to infants living in sub-Saharan Africa.


Eligibility criteria: Inclusion Criteria:

All subjects must satisfy ALL the following criteria at study entry:

* A male or female infant aged between 8 and 12 weeks inclusive at the time of first vaccination
* Signed or thumb-printed informed consent obtained from the parent(s)/Legally Acceptable Representative \[LAR(s)\] of the child. Where parent(s)/LAR(s) are illiterate, the consent form will be countersigned by an independent witness
* Subjects who the investigator believes that their parent(s)/LAR(s) can and will comply with the requirements of the protocol
* Healthy subjects as established by medical history and clinical examination before entering into the study
* Born to a mother who is Hepatitis B surface antigen (HBsAg) negative
* Born to a mother who is Human Immunodeficiency Virus (HIV) negative
* Born after a normal gestation period of 36 to 42 weeks inclusive.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

* Child in care
* Acute disease and/or fever 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
* Previous vaccination with diphtheria, tetanus, pertussis, Haemophilus influenzae type b, Streptococcus pneumoniae, hepatitis B vaccine or rotavirus vaccines.
* Planned administration/administration of a licensed vaccine not foreseen by the study protocol within 7 days of the first dose of study vaccine.
* Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Administration of immunoglobulins and/or any blood products in the period between birth and Dose 1 and within the three months preceding planned vaccine administration during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs in the period between birth and Dose 1.
* Concurrently participating in another clinical study at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
* Same sex twin
* Maternal death
* History of allergic reactions 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.
* Any other findings that the investigator feels would result in data collected being incomplete or of poor quality.
* Previous participation in any other malaria vaccine trial.

Primary outcomes:
measure: Percentage of Seroprotected Subjects Against Anti-Hepatitis B (HBs) Antigen
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-Hepatitis B (HBs) Antibody Concentrations for RTS,S Group and Engerix B Group
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-Hepatitis B (HBs) Antibody Concentrations for All Study Groups
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
Secondary outcomes:
measure: Anti-Hepatitis B (HBs) Antibody Concentrations at Month 3
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-Hepatitis B (HBs) Antibody Concentrations at Month 14 and 26
timeFrame: At Months 14 and 26, aka at 12 and 24 months post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-Hepatitis B (HBs) Antibody Concentrations at Month 38, 50 and 51
timeFrame: At Months 38, 50 and 51, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B and one month post the Month 50 booster dose of Engerix-B
measure: Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 3
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
measure: Concentrations of Antibodies to the Hepatitis B RF1 Surface Antigen (Anti-HBs RF1) at Month 51
timeFrame: At Month 51, aka one month post the Month 50 booster dose of Engerix-B
measure: Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 3
timeFrame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 14
timeFrame: At Month 14, aka at 12 months post Dose 3 of RTS,S vaccine or Engerix-B
measure: Anti-circumsporozoite Protein (Anti-CS) Antibody Concentrations at Month 38 and 50
timeFrame: At Months 38 and 50, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B
measure: Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 3
timeFrame: At Month 3, aka at one month post Dose 3 of Synflorix
measure: Pneumococcal Antibody Concentrations Against Synflorix Pneumococcal Vaccine Serotypes at Month 17
timeFrame: At Month 17, aka one month post the Month 16 booster dose of Synflorix
measure: Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 3
timeFrame: At Month 3, aka at one month (1M) post Dose 3 of Synflorix
measure: Titers for Opsonophagocytic Activity Against Synflorix Pneumococcal Vaccine Serotypes at Month 17
timeFrame: At Month 17, aka one month post the Month 16 booster dose of Synflorix
measure: Anti-protein D (PD) Antibody Concentrations at Month 3
timeFrame: At Month 3, aka at one month post Dose 3 of Synflorix
measure: Anti-protein D (PD) Antibody Concentrations at Month 17
timeFrame: At Month 17, aka one month post the Month 16 booster dose of Synflorix
measure: Concentrations of Antibodies Against Acellular B-pertussis (BPT) at Day 0 and at Month 3
timeFrame: At Day 0 and at Month 3 (one month post Dose 3 of Infanrix-Hib)
measure: Anti-Rotavirus (Anti-RV) Antibody Concentrations
timeFrame: At Month 3, aka one month post Dose 2 of Rotarix
measure: Number of Subjects With Solicited Local Symptoms
timeFrame: Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine
measure: Number of Subjects With Solicited General Symptoms
timeFrame: Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine
measure: Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 8
timeFrame: From Day 0 to Month 8
measure: Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 to Month 26
timeFrame: From Day 0 to Month 26
measure: Number of Subjects With Potential Immune Mediated Disorders (pIMDs) From Day 0 up to Study End (Month 51)
timeFrame: From Day 0 up to Study End (Month 51)
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
measure: Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) Within the 30-day Follow-up Periods (Days 0-29)
timeFrame: Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B
measure: Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 8
timeFrame: From Day 0 to Month 8
measure: Number of Subjects With Any and Fatal Serious Adverse Events (SAEs) From Day 0 to Month 26
timeFrame: From Day 0 to Month 26
measure: Number of Subjects With Any, Fatal and Related Serious Adverse Events (SAEs) From Day 0 up to Study End (Month 51)
timeFrame: From Day 0 up to Study End (Month 51)
Other outcomes:
Locations:
city: Ouagadougou 01
country: Burkina Faso
facility: GSK Investigational Site
city: Kumasi
country: Ghana
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Valea I, Adjei S, Usuf E, Traore O, Ansong D, Tinto H, Owusu Boateng H, Leach A, Mwinessobaonfou Some A, Buabeng P, Vekemans J, Nana LA, Kotey A, Vandoolaeghe P, Ouedraogo F, Sambian D, Lievens M, Tahita MC, Rettig T, Jongert E, Lompo P, Idriss A, Borys D, Ouedraogo S, Prempeh F, Habib MA, Schuerman L, Sorgho H, Agbenyega T. Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial. Hum Vaccin Immunother. 2018 Jun 3;14(6):1489-1500. doi: 10.1080/21645515.2018.1442996. Epub 2018 Apr 13.