Clinical trial NCT02699099: Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Given at 6, 7.5 and 9 Months of Age in Co-administration With Measles, Rubella and Yellow Fever (YF) Vaccines Followed by a Booster of the Malaria Vaccine.
Official title: Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Given at 6, 7.5 and 9 Months of Age in Co-administration With Measles, Rubella and Yellow Fever Vaccines Followed by a Booster of the Malaria Vaccine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria
Malaria Vaccines
Keywords: Children
Infants
SB257049
Malaria
Immunogenicity
Surveillance
Efficacy
Safety
Africa
Plasmodium falciparum
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-03-04
Enrollment: 699
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the immunogenicity, safety, and reactogenicity of the SB257049 candidate malaria vaccine when co-administered with Vitamin A, measles, rubella and yellow fever vaccines to children aged 6 months at the first vaccination.


Eligibility criteria: Inclusion Criteria:

* Subjects' parent(s)/Legally Acceptable Representative(s) (LAR\[s\]) who, in the opinion of the investigator, could and complied with the requirements of the protocol.
* A male or female 6 months of age (from the day the child becomes 6 months of age until the day before the child achieved 7 months of age) at the time of the first vaccination.
* Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the subject. Where parent(s)/LAR(s) were illiterate, the consent form was countersigned by an independent witness.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Previously received three documented doses of diphtheria, tetanus, and whole-cell pertussis, hepatitis B vaccine (DTPwHepB), and a 3-dose course of oral polio vaccine and, if locally recommended, pneumococcal and rotavirus vaccines.

Exclusion Criteria:

* Child in care
* 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.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this meant prednisone≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids were allowed.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose of SB257049 measles, rubella and YF vaccines and ending 42 days after the last dose of vaccines given at 9 months of age (Visit 4), with the exception of oral polio vaccine which could be given for unforeseen public health threat.
* 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 vaccine/product.
* Previous vaccination against measles, YF or rubella.
* Previous administration of Vitamin A.
* Moderate or severe malnutrition at screening defined as weight for age Z-score \< -2.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). See also Section 1.3.
* Major congenital defects or serious chronic illness.
* History of any neurological disorders or seizures.
* Acute disease and/or fever at the time of enrolment. Fever was defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route. The preferred route for recording temperature in this study was axillary.

Subjects with a minor illness without fever might have been enrolled at the discretion of the investigator.

* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
* Same sex twin.
* Maternal death.
* Previous participation in any other malaria study.

Primary outcomes:
measure: Anti-Circumsporozoite (Anti-CS) Antibody Concentrations, One Month Post Dose 3 of SB257049 (Primary Analysis)
timeFrame: At one month post Dose 3 of SB257049 (Month 4)
measure: Anti-CS Antibody Concentrations, One Month Post Dose 3 of SB257049 (Study End Analysis)
timeFrame: At one month post Dose 3 of SB257049 (Month 4)
Secondary outcomes:
measure: Anti-CS Antibody Concentrations, Pre-vaccination and One Month Post Dose 3 of SB257049
timeFrame: At Day 0 and one month post Dose 3 of SB257049 (Month 4)
measure: Number of Seropositive Subjects for Anti-CS Antibodies, Pre-vaccination and One Month Post Dose 3 of SB257049
timeFrame: At Day 0 and one month post Dose 3 of SB257049 (Month 4)
measure: Anti-hepatitis B (Anti-HBs) Antibody Concentrations, Pre-vaccination and One Month Post-Dose 3 of SB257049
timeFrame: At Day 0 and one month post Dose 3 of SB257049 (Month 4)
measure: Number of Seroprotected Subjects for Anti-HB Antibodies, Pre-vaccination and One Month Post-Dose 3 of SB257049
timeFrame: At Day 0 and one month post-Dose 3 of SB257049 (Month 4)
measure: Number of Seroconverted Subjects for Anti-Measles (Anti-Me) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella (MeRu) Vaccine
timeFrame: At one month post-vaccination with the combined measles and rubella (MeRu) vaccine (Month 4)
measure: Anti-Me Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
timeFrame: At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)
measure: Number of Seropositive Subjects for Anti-Me Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
timeFrame: At pre-vaccination (Month 3) and one month post-vaccination with the combined measles and rubella vaccine (Month 4)
measure: Number of Seroconverted Subjects for Anti-Rubella (Anti-Ru) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella Vaccine
timeFrame: At one month post-vaccination with combined measles and rubella vaccine (Month 4)
measure: Anti-Ru Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
timeFrame: At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)
measure: Number of Seropositive Subjects for Anti-Ru Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
timeFrame: At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)
measure: Number of Seropositive Subjects for Anti-Yellow Fever (Anti-YF) Antibodies, at One Month Post-vaccination With the YF Vaccine
timeFrame: At one month post-vaccination with the YF vaccine (Month 4)
measure: Anti-YF Antibody Titers One Month Post-vaccination With the YF Vaccine
timeFrame: At one month post-vaccination with the YF vaccine (Month 4)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age
timeFrame: During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)
measure: Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age
timeFrame: During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)
measure: Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Control Group After Administration of Vitamin A at 6 Months of Age
timeFrame: During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A (Day 0)
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age
timeFrame: During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)
measure: Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age
timeFrame: During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)
measure: Number of Subjects With Solicited General Symptoms for the Control Group, After Visit at 7.5 Months of Age
timeFrame: After visit at Month 1.5
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age
timeFrame: During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)
measure: Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age
timeFrame: During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)
measure: Number of Subjects With Unsolicited Adverse Events (AEs) for All Groups, After Administration of Vitamin A and Study Vaccines at 6 Months of Age
timeFrame: Within 30-day (Days 0-29) period after dose 1 of SB257049 and Vitamin A- Coad and RTS,S Groups, and 30-day period after Vitamin A administration - Control Group
measure: Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After Dose of Study Vaccines at 7.5 Months of Age
timeFrame: Within 30-day (Day of vaccination and 29 subsequent days) period after dose 2 of SB257049 administered at Month 1.5 - Coad and RTS,S Groups
measure: Number of Subjects With Unsolicited AEs for the Control Group, at Visit at 7.5 Months of Age
timeFrame: During the 30-day period (Day of the visit and 29 subsequent days) after the visit at Month 1.5
measure: Number of Subjects With Unsolicited AEs for All Study Groups, After Dose of Study Vaccines Administered at 9 Months of Age
timeFrame: Within 42-day (vaccination day and 41 subsequent days) period after dose 3 of SB257049 in Coad (+MeRu+YF vaccines) and RTS,S groups, and 42-day period after MeRU+YF vaccination in Control group, administered at Month 3
measure: Number of Subjects With Serious Adverse Events (SAEs): All, Fatal and Related, for All Study Groups, Following Each Administration at Day 0, Month1.5 and Month 3
timeFrame: During 30-Days period (Day of vaccination and 29 subsequent days) following each administration at Day 0, Month1.5 and Month 3 for Coad and RTS,S groups and at Day 0 and Month 3 in the Control Group.
measure: Number of Subjects With Any SAEs for All Study Groups, From Day 0 Until Month 4.5
timeFrame: From Day 0 up to Month 4.5
measure: Number of Subjects With Potential Immune-Mediated Disease (pIMDs) for All Study Groups From Day 0 Until Month 4.5
timeFrame: From Day 0 up to Month 4.5
measure: Number of Subjects With Meningitis for All Study Groups From Day 0 Until Month 4.5
timeFrame: From Day 0 up to Month 4.5
measure: Number of Subjects With Seizures for All Groups, Post-vaccination for Vaccines Administered at 6, 7.5 or 9 Months of Age
timeFrame: Within 30 days post-vaccination for vaccine doses administered at Day 0, Month 1.5 or 42 days post-vaccination (doses given at Month 3 [Coad & Control Groups] or Month 4.5 [RTS,S Group]) vaccination period from Day 0 until Month 4.5
measure: Number of Subjects With Generalized Convulsive Seizure for All Study Groups, After Vaccines Administered at Day 0 and Month 1.5 (Coad and RTS,S Groups) and After Vaccines Administered at Month 3 (All Groups)
timeFrame: Within 7 days after vaccines administered at Day 0 and Month 1.5 for the Coad and RTS,S groups and 14 days after vaccines administered at Month 3 for all groups
measure: Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After the Booster Dose of Study Vaccine Administered at 27 Months of Age
timeFrame: During the 30-day period (Day of vaccination and 29 subsequent days) after booster dose administered at Month 21
measure: Number of Subjects With Unsolicited AEs for the Control Group, After Dose of Study Vaccine Administered at 10.5, 11.5, 12.5 and 30 Months of Age
timeFrame: During the 30-Day Period (Day of vaccination and 29 subsequent days) after primary doses of study vaccine administered at Month 4.5, Month 5.5, Month 6.5 (across primary doses), and after booster dose administered at Month 24
measure: Number of Subjects With SAEs for All Study Groups From Day 0 Until Study End
timeFrame: During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)
measure: Number of Subjects With pIMDs for All Study Groups From Day 0 Until Study End
timeFrame: During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)
measure: Number of Subjects With Meningitis for All Study Groups From Day 0 Until Study End
timeFrame: During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)
measure: Number of Subjects With Seizures for Vaccines Doses Administered at 6, 7.5, 27 Months of Age for Coad and RTS,S Groups; and at 9 Months of Age for Coad Group or 10.5 Months of Age for RTS,S Group
timeFrame: Within 30 days post-vaccination (doses given at Day 0, Month 1.5, Month 21) & 42 days post-vaccination (dose given at Month 3 [Coad Group] or Month 4.5 [RTS,S Group])
measure: Number of Subjects With Seizures for Vaccines Doses Administered at 10.5, 11.5, 12.5, 30 and 9 Months of Age for Control Group
timeFrame: Within 30 days post-vaccination (doses given at Month 4.5, Month 5.5, Month 6.5, Month 24) & 42 days post-vaccination (dose given at Month 3)
Other outcomes:
Locations:
city: Kintampo
country: Ghana
facility: GSK Investigational Site
city: Kumasi
country: Ghana
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: