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Safety and Immunogenicity of GSK Biologicals' Investigational Malaria Vaccine in HIV Infected Infants and Children

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ClinicalTrials.gov Identifier: NCT01148459
Recruitment Status : Completed
First Posted : June 22, 2010
Results First Posted : January 16, 2019
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Malaria Biological: GSK Biological's Investigational Malaria Vaccine 257049 Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur); Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis). Phase 3

Detailed Description:
This protocol posting has been updated due to protocol Amendment 2.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Study of GSK Biologicals' Plasmodium Falciparum Malaria Vaccine 257049 Administered to HIV Infected Infants and Children
Study Start Date : July 30, 2010
Actual Primary Completion Date : May 24, 2013
Actual Study Completion Date : May 24, 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Malaria

Arm Intervention/treatment
Experimental: Group A
Infants enrolled to this group will receive 3 doses of the experimental vaccine.
Biological: GSK Biological's Investigational Malaria Vaccine 257049
All infants enrolled to group A will receive 3 doses of the experimental vaccine. The vaccine will be administered intramuscularly.

Active Comparator: Group B
Infants enrolled to this group will receive 3 doses of the rabies comparator vaccine.
Biological: Human Diploid Cell Vaccine (HDCV) or Purified Vero Cell Rabies Vaccine (PVRV, Verorab) (Aventis Pasteur);

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


Biological: Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine (Rabipur or equivalent) (Novartis).

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 Measures :
  1. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: 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 :
  1. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [ 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) ]
    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.

  2. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [ 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) ]
    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.

  3. Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: 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.

  4. Number of Subjects With Non-malaria Related SAEs [ Time Frame: 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.

  5. Anti-circumsporozoite Protein of P. Falciparum (Anti-CS) Antibody Concentrations [ Time Frame: 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.

  6. Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Titers [ Time Frame: 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).

  7. Anti-CS Antibody Concentrations [ Time Frame: 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.

  8. Anti-HBs Antibody Titers [ Time Frame: 12 months post Dose 3 (Month 14) ]
    Anti-HBs antibody titers are presented as geometric mean titers (GMTs), expressed in mIU/mL.

  9. Number of Episodes With Clinical Malaria Disease According to Primary Case Definition [ Time Frame: 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.

  10. Number of Episodes With Severe Malaria According to Primary Case Definition [ Time Frame: 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.

  11. Number of Subjects Affected by Prevalent Parasitemia and Prevalent Moderate Anemia [ Time Frame: 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.

  12. Asexual P. Falciparum Parasitemia Density [ Time Frame: 12 months post Dose 3 (Month 14) ]
    The number of subjects with a positive blood slide for asexual P. falciparum.

  13. Prevalent Hemoglobin Level [ Time Frame: 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).

  14. HIV Viral Load [ Time Frame: 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.

  15. Percentage of CD4+ Cells [ Time Frame: 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.

  16. CD4+ Absolute Cell Counts [ Time Frame: 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.

  17. World Health Organization (WHO) HIV Clinical Classification Progression [ 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 ]

    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".

  18. Growth Parameters: Weight, Age/Length and Middle Upper Arm Circumference for Age Z-score [ Time Frame: 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.



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Ages Eligible for Study:   6 Weeks to 17 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01148459


Locations
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Kenya
GSK Investigational Site
Kisian, Kenya
GSK Investigational Site
Kisumu, Kenya
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 112745
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01148459     History of Changes
Other Study ID Numbers: 112745
First Posted: June 22, 2010    Key Record Dates
Results First Posted: January 16, 2019
Last Update Posted: January 16, 2019
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
Plasmodium falciparum
schedule
HIV
malaria vaccine
EPI
Africa

Additional relevant MeSH terms:
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Malaria
Protozoan Infections
Parasitic Diseases
Vaccines
Lactitol
Immunologic Factors
Physiological Effects of Drugs
Cathartics
Gastrointestinal Agents