Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children
- Conditions
- Malaria
- Interventions
- Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);Biological: GSK Biological's Investigational Malaria Vaccine 257049Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).
- Registration Number
- NCT01148459
- Lead Sponsor
- GlaxoSmithKline
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis). Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine. Group B Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur); Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine. Group A GSK Biological's Investigational Malaria Vaccine 257049 Infants enrolled to this group will receive 3 doses of the experimental vaccine.
- Primary Outcome Measures
Name Time Method Number of Subjects With Serious Adverse Events (SAEs) During the entire study period (from 30 days before Dose 1 up to Month 14) 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
Name Time Method Anti-circumsporozoite Protein of P. Falciparum (Anti-CS) Antibody Concentrations Prior to vaccination (PRE) and one month post Dose 3 (Month 3) 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.
Number of Episodes With Severe Malaria According to Primary Case Definition From Day 0 to Month 14 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.
Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Titers Prior to vaccination (PRE) and one month post Dose 3 (Month 3) Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in milliinternational units per milliliter (mIU/mL).
Anti-CS Antibody Concentrations 12 months post Dose 3 (Month 14) 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.
Number of Episodes With Clinical Malaria Disease According to Primary Case Definition From Day 0 to Month 14 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 Subjects Affected by Prevalent Parasitemia and Prevalent Moderate Anemia 12 months post Dose 3 (Month 14) The number of subjects affected by prevalent asexual P. falciparum parasitemia and prevalent moderate anemia. Moderate anemia = hemoglobin \< 8 g/dL.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms 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) 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) During the 30-day post-vaccination period (up to Day 90) 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.
Anti-HBs Antibody Titers 12 months post Dose 3 (Month 14) Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in mIU/mL.
Prevalent Hemoglobin Level 12 months post Dose 3 (Month 14) The prevalent hemoglobin level in subjects with a positive blood slide is reported as grams per deciliter (g/dl).
Number of Subjects With Any and Grade 3 Solicited Local Symptoms 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) 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 Non-malaria Related SAEs During the entire study period (from 30 days before vaccine Dose 1 up to Month 14) 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.
Asexual P. Falciparum Parasitemia Density 12 months post Dose 3 (Month 14) The number of subjects with a positive blood slide for asexual P. falciparum.
HIV Viral Load At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3 The HIV viral load is reported. Detectable HIV viral load: 400 or more copies/mL.
Percentage of CD4+ Cells At baseline (PRE) and at one month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3 The percentage of CD4+ cells is reported.
CD4+ Absolute Cell Counts At baseline (PRE) and at 1 month (Month 3), 6 months (Month 8) and 12 months (Month 14) post Dose 3 The CD4+ absolute cell counts are reported.
World Health Organization (WHO) HIV Clinical Classification Progression 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 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 At baseline (PRE), at Month 3 and at study end (Month 14) The following growth parameters: weight, age/length and middle upper arm circumference for age z-score are reported.
Trial Locations
- Locations (1)
GSK Investigational Site
🇰🇪Kisumu, Kenya