Back to resultsSafety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children
Primary Purpose
Malaria
Status
Completed
Phase
Phase 3
Locations
Kenya
Study Type
Interventional
Intervention
GSK Biological's Investigational Malaria Vaccine 257049
Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);
Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).
Sponsored by
About this trial
This is an interventional prevention trial for Malaria focused on measuring Plasmodium falciparum, schedule, HIV, malaria vaccine, EPI, Africa
Eligibility Criteria
Inclusion Criteria:
All subjects must satisfy ALL the following criteria at study entry:
- A male or female infant or child between and including 6 weeks to 17 months of age, at the time of first vaccination.
- Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the infant or child. Where parents/LARs are illiterate, the consent form will be countersigned by a witness.
- Subjects who the investigator believes that their parents/LARs can and will comply with the requirements of the protocol should be enrolled in the study.
- Subjects who are known to be HIV-infected (documented positive DNA PCR), whether taking HIV antiretroviral treatment (ART) or not.
- Subjects who are born following a normal gestation period.
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:
- Acute disease at the time of enrolment. However, the presence of an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging) will not of itself constitute an exclusion criterion. Enrolment should be deferred if axillary temperature is >=37.5°C.
- Grade III or Grade IV abnormality on screening laboratory blood sample.
- Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical staging).
- Major congenital defects.
- Planned administration/administration of a vaccine not foreseen by the study protocol prior to or within 7 days of study vaccine.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 30 days preceding Dose°1 of study vaccine, or planned use during the study period.
- Previous participation in any other malaria vaccine trial.
- Simultaneous participation in another clinical trial including administration of experimental treatment.
- Same sex twins.
- 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 study vaccine.
- Child in care.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group A
Group B
Arm Description
Infants enrolled to this group will receive 3 doses of the experimental vaccine.
Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine.
Outcomes
Primary Outcome Measures
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Secondary Outcome Measures
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond (>) 20 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Any Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Non-malaria Related SAEs
SAEs (excluding malaria, cerebral malaria and P. falciparum parasitemia) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Anti-circumsporozoite Protein of P. Falciparum (Anti-CS) Antibody Concentrations
Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Titers
Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in milliinternational units per milliliter (mIU/mL).
Anti-CS Antibody Concentrations
Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.
Anti-HBs Antibody Titers
Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in mIU/mL.
Number of Episodes With Clinical Malaria Disease According to Primary Case Definition
Primary case definition for clinical malaria: P. falciparum asexual parasitemia > 2500 parasites/μL and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who was unwell and brought for treatment to a healthcare facility.
Number of Episodes With Severe Malaria According to Primary Case Definition
The number of episodes of severe malaria of primary case definition within and outside risk period. Primary case definition for severe malaria: P. falciparum > 2500 parasites per μL and with one or more marker of disease severity and without a diagnosis of co-morbidity.
Number of Subjects Affected by Prevalent Parasitemia and Prevalent Moderate Anemia
The number of subjects affected by prevalent asexual P. falciparum parasitemia and prevalent moderate anemia. Moderate anemia = hemoglobin < 8 g/dL.
Asexual P. Falciparum Parasitemia Density
The number of subjects with a positive blood slide for asexual P. falciparum.
Prevalent Hemoglobin Level
The prevalent hemoglobin level in subjects with a positive blood slide is reported as grams per deciliter (g/dl).
HIV Viral Load
The HIV viral load is reported. Detectable HIV viral load: 400 or more copies/mL.
Percentage of CD4+ Cells
The percentage of CD4+ cells is reported.
CD4+ Absolute Cell Counts
The CD4+ absolute cell counts are reported.
World Health Organization (WHO) HIV Clinical Classification Progression
Clinical staging was done at each time point according to the WHO HIV/AIDS clinical staging system. Clinical stages included:
"Stage 1" (asymptomatic or have persistent generalized lymphadenopathy),
"Stage 2" (mildly symptomatic stage - presenting with unexplained weight loss of less than 10 percent of total body weight, recurrent respiratory infections or dermatological conditions),
"Stage 3" (moderately symptomatic stage - presenting with weight loss of greater than 10 percent of total body weight, prolonged unexplained diarrhea or pulmonary tuberculosis, severe systemic bacterial infections or mucocutaneous conditions),
"Stage 4" (severely symptomatic stage which includes all of the AIDS-defining illnesses) Additional categories included "deceased" and "missing".
Growth Parameters: Weight, Age/Length and Middle Upper Arm Circumference for Age Z-score
The following growth parameters: weight, age/length and middle upper arm circumference for age z-score are reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01148459
Brief Title
Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children
Official Title
Safety and Immunogenicity Study of GSK Biologicals' Plasmodium Falciparum Malaria Vaccine 257049 Administered to HIV Infected Infants and Children
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
July 30, 2010 (undefined)
Primary Completion Date
May 24, 2013 (Actual)
Study Completion Date
May 24, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to assess the safety and immunogenicity of the candidate malaria vaccine in HIV-infected infants and children
Detailed Description
This protocol posting has been updated due to protocol Amendment 2.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Plasmodium falciparum, schedule, HIV, malaria vaccine, EPI, Africa
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Description
Infants enrolled to this group will receive 3 doses of the experimental vaccine.
Arm Title
Group B
Arm Type
Active Comparator
Arm Description
Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine.
Intervention Type
Biological
Intervention Name(s)
GSK Biological's Investigational Malaria Vaccine 257049
Intervention Description
All infants enrolled to group A will receive 3 doses of the experimental vaccine. The vaccine will be administered intramuscularly.
Intervention Type
Biological
Intervention Name(s)
Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);
Intervention Description
To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.
The vaccine will be administered intramuscularly
Intervention Type
Biological
Intervention Name(s)
Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).
Intervention Description
To ensure consistent vaccine availability, three cell culture rabies vaccines from two manufacturers may be sourced for this trial (Aventis-Pasteur and Novartis). It will be ensured that an individual child will receive all 3 doses of cell culture rabies vaccine from the same product.
The vaccine will be administered intramuscularly.
Primary Outcome Measure Information:
Title
Number of Subjects With Serious Adverse Events (SAEs)
Description
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the entire study period (from 30 days before Dose 1 up to Month 14)
Secondary Outcome Measure Information:
Title
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond (>) 20 millimeters (mm) of injection site.
Time Frame
During the 7-day post-vaccination period following each dose and across doses: Day 1 through Day 7, Month 1 through Month 1 + 7 days (Day 37), Month 2 through Month 2 + 7 days (Day 67)
Title
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description
Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Time Frame
During the 7-day post-vaccination period following each dose and across doses: Day 1 through Day 7, Month 1 through Month 1 + 7 days (Day 37), Month 2 through Month 2 + 7 days (Day 67)
Title
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Description
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame
During the 30-day post-vaccination period (up to Day 90)
Title
Number of Subjects With Non-malaria Related SAEs
Description
SAEs (excluding malaria, cerebral malaria and P. falciparum parasitemia) assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time Frame
During the entire study period (from 30 days before vaccine Dose 1 up to Month 14)
Title
Anti-circumsporozoite Protein of P. Falciparum (Anti-CS) Antibody Concentrations
Description
Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.
Time Frame
Prior to vaccination (PRE) and one month post Dose 3 (Month 3)
Title
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Titers
Description
Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in milliinternational units per milliliter (mIU/mL).
Time Frame
Prior to vaccination (PRE) and one month post Dose 3 (Month 3)
Title
Anti-CS Antibody Concentrations
Description
Anti-CS antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The reference seropositivity cut-off value was equal to or above (≥) 0.5 EL.U/mL.
Time Frame
12 months post Dose 3 (Month 14)
Title
Anti-HBs Antibody Titers
Description
Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in mIU/mL.
Time Frame
12 months post Dose 3 (Month 14)
Title
Number of Episodes With Clinical Malaria Disease According to Primary Case Definition
Description
Primary case definition for clinical malaria: P. falciparum asexual parasitemia > 2500 parasites/μL and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation and occurring in a child who was unwell and brought for treatment to a healthcare facility.
Time Frame
From Day 0 to Month 14
Title
Number of Episodes With Severe Malaria According to Primary Case Definition
Description
The number of episodes of severe malaria of primary case definition within and outside risk period. Primary case definition for severe malaria: P. falciparum > 2500 parasites per μL and with one or more marker of disease severity and without a diagnosis of co-morbidity.
Time Frame
From Day 0 to Month 14
Title
Number of Subjects Affected by Prevalent Parasitemia and Prevalent Moderate Anemia
Description
The number of subjects affected by prevalent asexual P. falciparum parasitemia and prevalent moderate anemia. Moderate anemia = hemoglobin < 8 g/dL.
Time Frame
12 months post Dose 3 (Month 14)
Title
Asexual P. Falciparum Parasitemia Density
Description
The number of subjects with a positive blood slide for asexual P. falciparum.
Time Frame
12 months post Dose 3 (Month 14)
Title
Prevalent Hemoglobin Level
Description
The prevalent hemoglobin level in subjects with a positive blood slide is reported as grams per deciliter (g/dl).
Time Frame
12 months post Dose 3 (Month 14)
Title
HIV Viral Load
Description
The HIV viral load is reported. Detectable HIV viral load: 400 or more copies/mL.
Time Frame
At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3
Title
Percentage of CD4+ Cells
Description
The percentage of CD4+ cells is reported.
Time Frame
At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3
Title
CD4+ Absolute Cell Counts
Description
The CD4+ absolute cell counts are reported.
Time Frame
At baseline (PRE) and at 1 month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3
Title
World Health Organization (WHO) HIV Clinical Classification Progression
Description
Clinical staging was done at each time point according to the WHO HIV/AIDS clinical staging system. Clinical stages included:
"Stage 1" (asymptomatic or have persistent generalized lymphadenopathy),
"Stage 2" (mildly symptomatic stage - presenting with unexplained weight loss of less than 10 percent of total body weight, recurrent respiratory infections or dermatological conditions),
"Stage 3" (moderately symptomatic stage - presenting with weight loss of greater than 10 percent of total body weight, prolonged unexplained diarrhea or pulmonary tuberculosis, severe systemic bacterial infections or mucocutaneous conditions),
"Stage 4" (severely symptomatic stage which includes all of the AIDS-defining illnesses) Additional categories included "deceased" and "missing".
Time Frame
At baseline (PRE), at study months 1 (Month 1) and 2 (Month 2) and at 1 month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3
Title
Growth Parameters: Weight, Age/Length and Middle Upper Arm Circumference for Age Z-score
Description
The following growth parameters: weight, age/length and middle upper arm circumference for age z-score are reported.
Time Frame
At baseline (PRE), at Month 3 and at study end (Month 14)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Weeks
Maximum Age & Unit of Time
17 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All subjects must satisfy ALL the following criteria at study entry:
A male or female infant or child between and including 6 weeks to 17 months of age, at the time of first vaccination.
Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the infant or child. Where parents/LARs are illiterate, the consent form will be countersigned by a witness.
Subjects who the investigator believes that their parents/LARs can and will comply with the requirements of the protocol should be enrolled in the study.
Subjects who are known to be HIV-infected (documented positive DNA PCR), whether taking HIV antiretroviral treatment (ART) or not.
Subjects who are born following a normal gestation period.
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:
Acute disease at the time of enrolment. However, the presence of an illness listed as Grade I or Grade II (WHO pediatric AIDS clinical staging) will not of itself constitute an exclusion criterion. Enrolment should be deferred if axillary temperature is >=37.5°C.
Grade III or Grade IV abnormality on screening laboratory blood sample.
Grade III or IV AIDS at the time of enrolment (WHO pediatric AIDS clinical staging).
Major congenital defects.
Planned administration/administration of a vaccine not foreseen by the study protocol prior to or within 7 days of study vaccine.
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 30 days preceding Dose°1 of study vaccine, or planned use during the study period.
Previous participation in any other malaria vaccine trial.
Simultaneous participation in another clinical trial including administration of experimental treatment.
Same sex twins.
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 study vaccine.
Child in care.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Kisian
Country
Kenya
Facility Name
GSK Investigational Site
City
Kisumu
Country
Kenya
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
27394191
Citation
Otieno L, Oneko M, Otieno W, Abuodha J, Owino E, Odero C, Mendoza YG, Andagalu B, Awino N, Ivinson K, Heerwegh D, Otsyula N, Oziemkowska M, Usuf EA, Otieno A, Otieno K, Leboulleux D, Leach A, Oyieko J, Slutsker L, Lievens M, Cowden J, Lapierre D, Kariuki S, Ogutu B, Vekemans J, Hamel MJ. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial. Lancet Infect Dis. 2016 Oct;16(10):1134-1144. doi: 10.1016/S1473-3099(16)30161-X. Epub 2016 Jul 7.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112745
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children
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