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A Study of Safety, Reactogenicity and Immunogenicity of HRV Vaccine in HIV Infected Infants in South Africa

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00263666
First received: December 8, 2005
Last updated: November 9, 2016
Last verified: November 2016
  Purpose
The aim of this study is to evaluate the reactogenicity, safety and immunogenicity of GSK Biologicals' human rotavirus (HRV) vaccine given concomitantly with routine vaccines including OPV in HIV positive infants. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition Intervention Phase
Infections, Rotavirus
Biological: Rotarix
Biological: Placebo
Biological: TritanrixTM-HB+Hib
Biological: SabinPolioTM vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase II, Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Reactogenicity and Immunogenicity of Three Doses of GlaxoSmithKline (GSK) Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting Grade "2" or Grade "3" Fever, Vomiting or Diarrhea. [ Time Frame: Within the 15-day solicited follow-up period after any dose. ]

    Symptoms reported in the table include:

    Fever: temperature (axillary route) > 38.0 degree Celsius (°C); Diarrhea: ≥ 4 looser than normal stools/day; Vomiting: ≥ 2 episodes of vomiting/day.



Secondary Outcome Measures:
  • Number of Subjects Reporting Any Unsolicited Symptoms. [ Time Frame: Within 30 days after each dose ]
    An unsolicited symptom was any spontaneously reported untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  • Number of Subjects Reporting Any Serious Adverse Events. [ Time Frame: Until 2 months after dose 3 (for subjects RV negative at Day 42 post-dose 3) or until end of RV shedding (for subjects who shed RV at Day 42 post-dose 3). ]

    A serious adverse event (SAE) is any untoward medical occurrence that:

    results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.


  • Number of Subjects Reporting Each Type of Solicited Symptom. [ Time Frame: Within the 15-day solicited follow-up period after each dose ]
    Solicited symptoms included Cough, Diarrhea (3 or more looser than normal stools/day), Fever (axillary temperature ≥ 37.5°C), Irritability, Loss of appetite, and Vomiting.

  • The Number of Subjects With no Evidence of Immunosuppression and Moderate/ Severe Suppression, Based on CD4+ Absolute Cell Count and CD4+ Percent. [ Time Frame: At the screening visit and 2 months after dose 3 (Visit 4). ]
    Severe suppression: CD4+ cells/microliter (μl) < 750 and CD4+ percent < 15 percent (%); No evidence of suppression: CD4+ cells/μl ≥ 1500 and CD4+ percent ≥ 25%; Moderate suppression = all other CD4+ cell count and CD4+ % combinations.

  • Human Immunodeficiency Virus (HIV) Viral Load [ Time Frame: At the screening visit and 2 months after dose 3. ]
    Mean and standard deviation of the base-10 logarithm of HIV-1 ribonucleic acid (RNA) copies per milliliter (mL).

  • Number of Subjects Who Seroconverted Against Rotavirus [ Time Frame: Two months after dose 3 ]
    A subject with anti-rotavirus Immunoglobulin (IgA) antibody concentration < 20 units/milliliter (U/mL) before vaccination and ≥ 20 U/mL after vaccination is considered as seroconverted.

  • Number of Subjects With Vaccine Take. [ Time Frame: Two months after the dose 3 ]
    Vaccine take: appearance of serum IgA to rotavirus at a concentration of ≥ 20 U/ml or rotavirus shedding in any stool sample collected from the Screening Visit to 2 months after dose 3 for subjects initially negative for rotavirus.

  • Serum Rotavirus Immunoglobulin A (IgA) Antibody Concentrations. [ Time Frame: Two months after dose 3 ]
    Concentrations are given as geometric mean concentrations (GMC) for anti-rotavirus IgA antibodies.

  • Number of Subjects With Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations More Than or Equal to the Cut-off Value. [ Time Frame: Two months after dose 3 ]
    Cut-off values for anti-PRP antibody concentrations were ≥ 0.15 and ≥ 1.0 microgram/milliliter (µg/mL).

  • Geometric Mean Concentration for Anti-PRP Antibodies. [ Time Frame: Two months after dose 3 ]
  • Number of Subjects With Anti-diphtheria and Anti-tetanus Toxoids Antibody Concentrations More Than or Equal to the Cut-off Value [ Time Frame: Two months after dose 3 ]
    The cut-off value was ≥ 0.1 International Units/milliliter (IU/mL)

  • Geometric Mean Concentration for Anti-diphtheria and Anti-tetanus Toxoids Antibodies. [ Time Frame: Two months after dose 3 ]
  • Number of Subjects With Anti-hepatitis B (HBs) Antibody Concentrations More Than or Equal to the Cut-off Value [ Time Frame: Two months after dose 3 ]
    The cut-off value was ≥ 10 milli international units/milliliter (mIU/mL).

  • Geometric Mean Concentration for Anti-HBs Antibodies. [ Time Frame: Two months after dose 3 ]
  • Number of Subjects With Anti-Bordetella Pertussis (BPT) Antibody Concentrations More Than or Equal to the Cut-off Value [ Time Frame: Two months after dose 3 ]
    The cut-off value was ≥ 15 Enzyme Linked Immunosorbent Assay Unit/milliliter(EL.U/mL).

  • Geometric Mean Concentration for Anti-BPT Antibodies. [ Time Frame: Two months after dose 3 ]
  • Number of Subjects With Anti-polio Types 1, 2 and 3 Antibody Titers More Than or Equal to the Cut-off Value [ Time Frame: Two months after dose 3 ]
    The cut-off value was ≥ 1:8. The lowest dilution at which serum samples were tested was 1:8, from which a test was considered positive.

  • Geometric Mean Titer for Anti-polio Types 1, 2 and 3 Antibodies. [ Time Frame: Two months after dose 3 ]
  • Rotavirus Antigen Excretion in Stool Samples [ Time Frame: At day of each vaccination and at planned days following each vaccine dose until 2 months after dose 3 or until end of RV shedding ]
    Number of subjects with rotavirus detected by Enzyme Linked Immunosorbent Assay (ELISA) in stool samples collected from Dose 1 until study end

  • Rotavirus in Diarrheal Stool Samples [ Time Frame: From Dose 1 until 2 months after dose 3 or until end of RV shedding ]
    Number of subjects reporting at least one rotavirus (vaccine strain or wild type rotavirus) gastroenteritis episode.

  • Rotavirus Vaccine Strain Identification. [ Time Frame: From dose 1 until 2 months after dose 3 or until end of RV shedding ]

    Number of gastroenteritis (GE) episodes classified by rotavirus vaccine strain/serotype.

    Unknown: These samples were typed post hoc and found "G1P8" vaccine type for one subject in HRV group, "G3P8" and "G2P4" for subjects in placebo group.


  • Enteric Pathogens Identification. [ Time Frame: From Dose 1 until 2 months after dose 3 or until end of RV shedding ]
    Number of gastroenteritis (GE) episodes classified by enteric pathogen tests results.

  • Number of Subjects With the RV in Stool Samples [ Time Frame: From Dose 1 until post Dose 3 ]
    Number of subjects with presence of RV in stool samples (shedding) collected at pre-determined time points by RV type (Yes, No, Mixed type and results not available [NA]).


Enrollment: 100
Study Start Date: March 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotarix Group
Subjects received 3 dose of Rotarix vaccine co-administered with routine Tritanrix TM, HepB Hib and Polio Sabin TM vaccines.
Biological: Rotarix
Oral vaccination
Biological: TritanrixTM-HB+Hib
Concomitant routine vaccination, IM administration
Biological: SabinPolioTM vaccine
Oral administration, concomitant routine vaccination
Placebo Comparator: Placebo Group
Subjects received 3 dose of placebo co-administered with routine Tritanrix TM, HepB Hib and Polio Sabin TM vaccines.
Biological: Placebo
Oral administration
Biological: TritanrixTM-HB+Hib
Concomitant routine vaccination, IM administration
Biological: SabinPolioTM vaccine
Oral administration, concomitant routine vaccination

Detailed Description:
HIV infected infants as determined prior to study entry (screening) and asymptomatic or mildly symptomatic (WHO stages I and II) of disease will be enrolled. The study will have two groups: Group HRV and Group Placebo. Three-dose immunisation will be administered at approximately 6, 10, and 14 weeks of age. Routine EPI (Expanded Program on Immunisation) vaccinations will be administered concomitantly with the study vaccines. At the time of first dose, subjects will be aged 6 to 10 weeks. This study will evaluate safety, reactogenicity and immunogenicity of the HRV vaccine relative to the placebo.
  Eligibility

Ages Eligible for Study:   6 Weeks to 10 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
  • A male or female between, and including 6 and 10 weeks of age at the time of the first vaccination.
  • Written informed consent obtained from the parents or guardians of the subject
  • Documented HIV status of the subject as confirmed by PCR.
  • HIV asymptomatic and HIV mildly symptomatic; Stages I and II disease according to WHO's most recent classification for HIV stages in infants and children.
  • Born after a gestation period of 36 to 42 weeks.

Exclusion Criteria:

  • Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Previous routine vaccination except OPV, BCG and HBV vaccination at birth
  • Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract or other serious medical condition as determined by the investigator.
  • History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
  • Acute disease at time of enrolment.
  • Gastroenteritis within 7 days preceding the study vaccine administration.
  • Previous confirmed occurrence of RV gastroenteritis.
  • Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes.
  • HIV moderately and severely symptomatic: stages III and IV according to WHO's recent classification.
  • Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00263666

Locations
South Africa
GSK Investigational Site
Attridgerville, Gauteng, South Africa, 0008
GSK Investigational Site
Coronationville, Gauteng, South Africa, 2112
GSK Investigational Site
Garankuwa, North-West, South Africa, 0204
GSK Investigational Site
Brits, South Africa, 0250
GSK Investigational Site
Capital Park, South Africa, 0002
GSK Investigational Site
Ga-Rankuwa, South Africa, 0208
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 444563/022
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: 444563/022
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: 444563/022
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: 444563/022
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 444563/022
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 444563/022
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):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00263666     History of Changes
Other Study ID Numbers: 444563/022 
Study First Received: December 8, 2005
Results First Received: February 13, 2009
Last Updated: November 9, 2016
Individual Participant Data  
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.

Additional relevant MeSH terms:
Rotavirus Infections
Reoviridae Infections
RNA Virus Infections
Virus Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 23, 2017