Clinical trial NCT01231503: Safety and Immunogenicity of GSK Biologicals' Malaria Vaccine 257049 When Administered on 7 Schedules to African Infants
Official title: Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine 257049 When Administered on Different Schedules to Infants in Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria
Keywords: Africa
malaria vaccine
schedule
EPI
Plasmodium falciparum
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: The PATH Malaria Vaccine Initiative (MVI)
First posted: 2010-11-01
Enrollment: 480
Sex: ALL
Minimum age (years): 1
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of the malaria vaccine program of the MVI/GSK partnership is to develop an efficacious malaria vaccine that is deliverable through the existing system, the Expanded Program on Immunization (EPI) of WHO. This study has been designed to:

* Investigate the safety and immunogenicity of 7 infant immunization schedules of the experimental malaria vaccine integrated with an EPI regimen.
* Investigate how to maximize the antibody response to the experimental malaria vaccine.


Eligibility criteria: Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

* A male or female infant between 1 and 7 days (inclusive) of age (where day 1 is day of birth).
* 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 the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.
* Born to a mother negative for HIV antibody and Hepatitis B surface antigen.
* Subjects who are born after a normal gestation period (between 37 and 42 weeks) (Gestational age will be determined by carrying out a clinical assessment on infants according to the principles set out by Dubowitz (1970) in the first 5 days of life).
* A minimum weight of 2.5 kg.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

* Acute or chronic illness determined by clinical or physical examination and laboratory screening tests including, but not limited to:

  * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  * A family history of congenital or hereditary immunodeficiency.
  * Major congenital defects.
  * History of any neurological disorders or seizures.
* Laboratory screening tests out of normal ranges/limits defined per protocol.
* Previous vaccination with diphtheria, tetanus, pertussis (whole-cell or acellular), Hemophilus influenzae type b, hepatitis B, BCG tuberculosis, measles or oral polio vaccines.
* Planned administration/administration of a licensed vaccine (i.e. a vaccine that is approved by one of the following authorities: FDA or EU member state or WHO \[with respect to prequalification\]) not foreseen by the study protocol within 7 days of the first dose of study vaccine.
* 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.
* Use of a drug or vaccine that is not approved for that indication (by one of the following authorities: FDA or EU member state or WHO \[with respect to prequalification\]) other than the study vaccine starting at birth or planned use during the study period.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
* Simultaneous participation in any other clinical trial.
* Same-sex 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.
* Children will not be enrolled if any maternal, obstetrical or neonatal event that has occurred might, in the judgment of the investigator, result in increased neonatal/infant morbidity
* 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 Reported With Serious Adverse Events (SAEs)
timeFrame: From study start at Month 0 up to Month 10.
measure: Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
timeFrame: At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M5 for RTS,S Neo-10-14, RTS,S 6-10-14 and Engerix-B Neo groups
measure: Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
timeFrame: At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M7 for RTS,S Neo-10-26, RTS,S 6-10-26, Engerix-B Neo/RTS,S 6-10-26, and RTS,S 10-14-26 groups
measure: Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
timeFrame: At 1 month (M) post Dose 3 of RTS,S/AS01E, e. a. M10 for RTS,S 14-26-9M Group
Secondary outcomes:
measure: Number of Subjects Reported With Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (Days 0-29) post vaccination period following 3 doses of RTS,S/AS01E versus DTPwHepB/Hib for the Engerix-B Neo Group
measure: Number of Subjects Reported With Serious Adverse Events (SAEs)
timeFrame: From study start at Month 0 up to Month 18 (corresponding data lock point =23 March 2015)
measure: Number of Subjects Reported With Biochemical Abnormalities, for the Alanine Aminotransferase (ALT) Parameter
timeFrame: At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
measure: Number of Subjects Reported With Biochemical Abnormalities, for the Creatinine (CREA) Parameter
timeFrame: At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
measure: Number of Subjects Reported With Haematological Abnormalities, for the Haemoglobin (HAE) Parameter
timeFrame: At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
measure: Number of Subjects Reported With Haematological Abnormalities, for the Platelets (PLA) Parameter
timeFrame: At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
measure: Number of Subjects Reported With Haematological Abnormalities, for the White Blood Cells (WBC) Parameter
timeFrame: At Day 7 post dose 1 (7D+W6) and at Day 30 post dose 3 (30D+W14).
measure: Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
timeFrame: At Screening (SCR), at Month (M) 4, at M5, at M7 and/or at M10, according to the vaccination scheduling for the specific group assessed concerned group
measure: Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations.
timeFrame: At Screening (SCR), at Month 5 (M5), at Month 7 (M7) and at Month 10 (M10), according to the vaccination scheduling
measure: Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations
timeFrame: At Month 5
measure: Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations
timeFrame: At Month 5
measure: Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Concentrations
timeFrame: At Month 5
measure: Concentrations of Antibodies Against Acellular B-pertussis (BPT)
timeFrame: At Month 5
measure: Concentrations of Antibodies Against Measles Antigens
timeFrame: At Month 10
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 0 vaccination
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 6 vaccination
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 10 vaccination
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 14 vaccination
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 26 vaccination
measure: Number of Subjects Reported With Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after Month 9 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 0 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 6 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 10 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 14 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Week 26 vaccination
measure: Number of Subjects Reported With Solicited General Symptoms
timeFrame: Within 7 days (Days 0-6) after Month 9 vaccination
Other outcomes:
measure: Concentrations of Antibodies Against Circumsporozoite Protein of Plasmodium Falciparum (Anti-CS Antibodies)
timeFrame: At Month 18 post vaccination
measure: Anti-Hepatitis B Surface Antibody (Anti-HBs) Concentrations
timeFrame: At Month 18 post vaccination
Locations:
city: Bangwe, Blantyre
country: Malawi
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Witte D, Cunliffe NA, Turner AM, Ngulube E, Ofori-Anyinam O, Vekemans J, Chimpeni P, Lievens M, Wilson TP, Njiram'madzi J, Mendoza YG, Leach A. Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS,S/AS01E Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen: A Phase II, Single-Center, Open, Controlled Trial in Infants in Malawi. Pediatr Infect Dis J. 2018 May;37(5):483-491. doi: 10.1097/INF.0000000000001937.