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

Phase 2

Completed

• Conditions: Infections, Rotavirus
• Interventions: Biological: Placebo; Biological: Rotarix; Biological: Tritanrix-HB+Hib; Biological: Polio Sabin

• Registration Number: NCT00263666
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2005-03-16
• Study First Submitted: 2005-12-08
• Study First Submitted QC: 2005-12-08
• Study First Posted: 2005-12-09
• Primary Completion: 2008-02-07
• Study Completion: 2008-02-13
• Results First Submitted: 2009-02-13
• Results First Submitted QC: 2009-03-12
• Results First Posted: 2009-03-13
• Status Verified: 2020-10
• Last Update Submitted: 2020-11-04
• Last Update Posted: 2020-11-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Placebo	Subjects received 3 doses of placebo co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.
Rotarix Group	Tritanrix-HB+Hib	Subjects received 3 doses of Rotarix vaccine co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.
Placebo Group	Polio Sabin	Subjects received 3 doses of placebo co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.
Rotarix Group	Rotarix	Subjects received 3 doses of Rotarix vaccine co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.
Rotarix Group	Polio Sabin	Subjects received 3 doses of Rotarix vaccine co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.
Placebo Group	Tritanrix-HB+Hib	Subjects received 3 doses of placebo co-administered with routine Tritanrix HepB Hib and Polio Sabin vaccines.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Grade "2" or Grade "3" Fever, Vomiting or Diarrhea	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

Name	Time	Method
The Number of Subjects With no Evidence of Immunosuppression and Moderate/ Severe Suppression, Based on CD4+ Absolute Cell Count and CD4+ Percent	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	At the screening visit and 2 months after dose 3	The HIV viral load was expressed as mean and standard deviation of the base-10 logarithm of HIV-1 ribonucleic acid (RNA) copies per milliliter (mL).
Number of Subjects Reporting Any Unsolicited Symptoms	Within 30 days after any 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 With Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations More Than or Equal to the Cut-off Value	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-HBs Antibodies	Two months after dose 3	Anti-HBs antibody concentrations are presented as geometric mean concentrations, expressed in milli international units/milliliter (mIU/mL).
Geometric Mean Concentration for Anti-PRP Antibodies	Two months after dose 3	Anti-PRP antibody concentrations are presented as geometric mean concentrations, expressed in microgram/milliliter (μg/mL).
Geometric Mean Concentration for Anti-diphtheria and Anti-tetanus Toxoids Antibodies	Two months after dose 3	Anti-diphteria and anti-tetanus toxoids antibody concentrations are presented as geometric mean concentrations, expressed in international units/milliliter (IU/mL).
Rotavirus in Diarrheal Stool Samples	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.
Enteric Pathogens Identification	From Dose 1 until 2 months after dose 3 or until end of RV shedding	Number of subjects reporting gastroenteritis (GE) episodes classified by enteric pathogen tests results.
Number of Subjects With the RV in Stool Samples	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 = G1V+G1WT+G2+G3+P4+P8V+P8WT and results not available \[NA\]).
Number of Subjects Reporting Each Type of Solicited Symptom	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.
Number of Subjects Who Seroconverted Against Rotavirus	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.
Serum Rotavirus Immunoglobulin A (IgA) Antibody Concentrations	Two months after dose 3	Concentrations are given as geometric mean concentrations (GMC) for anti-rotavirus IgA antibodies.
Number of Subjects With Anti-diphtheria and Anti-tetanus Toxoids Antibody Concentrations More Than or Equal to the Cut-off Value	Two months after dose 3	The cut-off value was ≥ 0.1 International Units/milliliter (IU/mL).
Number of Subjects With Anti-hepatitis B (HBs) Antibody Concentrations More Than or Equal to the Cut-off Value	Two months after dose 3	The cut-off value was ≥ 10 milli international units/milliliter (mIU/mL).
Number of Subjects With Anti-polio Types 1, 2 and 3 Antibody Titers More Than or Equal to the Cut-off Value	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.
Number of Subjects Reporting Any Serious Adverse Events	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 With Vaccine Take	Two months after 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.
Geometric Mean Titer for Anti-polio Types 1, 2 and 3 Antibodies.	Two months after dose 3	Anti-polio types 1, 2 and 3 antibody titers are presented as geometric mean titers.
Number of Subjects With Anti-Bordetella Pertussis (BPT) Antibody Concentrations More Than or Equal to the Cut-off Value	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	Two months after dose 3	Anti-BPT antibody concentrations are presented as geometric mean concentrations, expressed in ELISA units/milliliter (EL.U/mL).
Rotavirus Antigen Excretion in Stool Samples	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 Vaccine Strain Identification	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇿🇦 Ga-Rankuwa, South Africa