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Phase 3 N=699 Randomized Prevention

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.

Malaria · Malaria Vaccines

Enrolled (actual)
699
Serious AEs
27.0%
Results posted
Aug 2019
Primary outcome: Primary: Anti-Circumsporozoite (Anti-CS) Antibody Concentrations, One Month Post Dose 3 of SB257049 (Primary Analysis) — 452.87; 422.49 EU/mL

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Vitamin A (Dietary_supplement); Candidate Plasmodium falciparum malaria vaccine (Biological); MR-Vac (Biological); Stamaril (Biological)
Age
Pediatric · 0+ yrs
Sex
All
Sponsor
GlaxoSmithKline
Primary completion
Mar 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Anti-Circumsporozoite (Anti-CS) Antibody Concentrations, One Month Post Dose 3 of SB257049 (Primary Analysis)
452.87; 422.49
PRIMARY
Anti-CS Antibody Concentrations, One Month Post Dose 3 of SB257049 (Study End Analysis)
454.51; 422.49
SECONDARY
Anti-CS Antibody Concentrations, Pre-vaccination and One Month Post Dose 3 of SB257049
0.96; 0.96; 454.51; 422.49
SECONDARY
Number of Seropositive Subjects for Anti-CS Antibodies, Pre-vaccination and One Month Post Dose 3 of SB257049
1; 2; 207; 213
SECONDARY
Anti-hepatitis B (Anti-HBs) Antibody Concentrations, Pre-vaccination and One Month Post-Dose 3 of SB257049
397.36; 427.65; 42162.55; 43261.19
SECONDARY
Number of Seroprotected Subjects for Anti-HB Antibodies, Pre-vaccination and One Month Post-Dose 3 of SB257049
196; 201; 205; 210
SECONDARY
Number of Seroconverted Subjects for Anti-Measles (Anti-Me) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella (MeRu) Vaccine
197; 212
SECONDARY
Anti-Me Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
75.00; 75.00; 565.81; 572.09
SECONDARY
Number of Seropositive Subjects for Anti-Me Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
0; 0; 200; 213
SECONDARY
Number of Seroconverted Subjects for Anti-Rubella (Anti-Ru) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella Vaccine
199; 212
SECONDARY
Anti-Ru Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
2.08; 2.09; 39.36; 42.45
SECONDARY
Number of Seropositive Subjects for Anti-Ru Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
5; 4; 207; 217
SECONDARY
Number of Seropositive Subjects for Anti-Yellow Fever (Anti-YF) Antibodies, at One Month Post-vaccination With the YF Vaccine
203; 214
SECONDARY
Anti-YF Antibody Titers One Month Post-vaccination With the YF Vaccine
324.31; 346.60
SECONDARY
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
25; 16; 0; 1; 7; 13
SECONDARY
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
4; 4; 0; 0; 0; 0
SECONDARY
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
1; 0; 0; 0; 6; 1
SECONDARY
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
3; 12; 0; 0; 4; 2
SECONDARY
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
6; 5; 0; 0; 1; 2
SECONDARY
Number of Subjects With Solicited General Symptoms for the Control Group, After Visit at 7.5 Months of Age
SECONDARY
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
10; 10; 1; 0; 0; 0
SECONDARY
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
7; 6; 0; 0; 0; 0
SECONDARY
Number of Subjects With Unsolicited Adverse Events (AEs) for All Groups, After Administration of Vitamin A and Study Vaccines at 6 Months of Age
116; 119; 111
SECONDARY
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
107; 109
SECONDARY
Number of Subjects With Unsolicited AEs for the Control Group, at Visit at 7.5 Months of Age
80
SECONDARY
Number of Subjects With Unsolicited AEs for All Study Groups, After Dose of Study Vaccines Administered at 9 Months of Age
120; 121; 125
SECONDARY
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
13; 8; 16; 1; 0; 1
SECONDARY
Number of Subjects With Any SAEs for All Study Groups, From Day 0 Until Month 4.5
14; 12; 21
SECONDARY
Number of Subjects With Potential Immune-Mediated Disease (pIMDs) for All Study Groups From Day 0 Until Month 4.5
0; 0; 0
SECONDARY
Number of Subjects With Meningitis for All Study Groups From Day 0 Until Month 4.5
0; 0; 0
SECONDARY
Number of Subjects With Seizures for All Groups, Post-vaccination for Vaccines Administered at 6, 7.5 or 9 Months of Age
0; 0; 0
SECONDARY
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)
0; 0; 0
SECONDARY
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
62; 67
SECONDARY
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
160; 57
SECONDARY
Number of Subjects With SAEs for All Study Groups From Day 0 Until Study End
61; 62; 66
SECONDARY
Number of Subjects With pIMDs for All Study Groups From Day 0 Until Study End
0; 1; 0
SECONDARY
Number of Subjects With Meningitis for All Study Groups From Day 0 Until Study End
0; 1; 1
SECONDARY
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
0; 0
SECONDARY
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
1

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02699099). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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