Clinical trial NCT00263666: A Study of Safety, Reactogenicity and Immunogenicity of HRV Vaccine in HIV Infected Infants in South Africa
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Rotavirus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-12-09
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Number of Subjects Reporting Grade "2" or Grade "3" Fever, Vomiting or Diarrhea
timeFrame: Within the 15-day solicited follow-up period after any dose
Secondary outcomes:
measure: Number of Subjects Reporting Any Unsolicited Symptoms
timeFrame: Within 30 days after any dose
measure: Number of Subjects Reporting Any Serious Adverse Events
timeFrame: 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)
measure: Number of Subjects Reporting Each Type of Solicited Symptom
timeFrame: Within the 15-day solicited follow-up period after each dose
measure: The Number of Subjects With no Evidence of Immunosuppression and Moderate/ Severe Suppression, Based on CD4+ Absolute Cell Count and CD4+ Percent
timeFrame: At the screening visit and 2 months after dose 3 (Visit 4)
measure: Human Immunodeficiency Virus (HIV) Viral Load
timeFrame: At the screening visit and 2 months after dose 3
measure: Number of Subjects Who Seroconverted Against Rotavirus
timeFrame: Two months after dose 3
measure: Number of Subjects With Vaccine Take
timeFrame: Two months after dose 3
measure: Serum Rotavirus Immunoglobulin A (IgA) Antibody Concentrations
timeFrame: Two months after dose 3
measure: Number of Subjects With Anti-polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations More Than or Equal to the Cut-off Value
timeFrame: Two months after dose 3
measure: Geometric Mean Concentration for Anti-PRP Antibodies
timeFrame: Two months after dose 3
measure: Number of Subjects With Anti-diphtheria and Anti-tetanus Toxoids Antibody Concentrations More Than or Equal to the Cut-off Value
timeFrame: Two months after dose 3
measure: Geometric Mean Concentration for Anti-diphtheria and Anti-tetanus Toxoids Antibodies
timeFrame: Two months after dose 3
measure: Number of Subjects With Anti-hepatitis B (HBs) Antibody Concentrations More Than or Equal to the Cut-off Value
timeFrame: Two months after dose 3
measure: Geometric Mean Concentration for Anti-HBs Antibodies
timeFrame: Two months after dose 3
measure: Number of Subjects With Anti-Bordetella Pertussis (BPT) Antibody Concentrations More Than or Equal to the Cut-off Value
timeFrame: Two months after dose 3
measure: Geometric Mean Concentration for Anti-BPT Antibodies
timeFrame: Two months after dose 3
measure: Number of Subjects With Anti-polio Types 1, 2 and 3 Antibody Titers More Than or Equal to the Cut-off Value
timeFrame: Two months after dose 3
measure: Geometric Mean Titer for Anti-polio Types 1, 2 and 3 Antibodies.
timeFrame: Two months after dose 3
measure: Rotavirus Antigen Excretion in Stool Samples
timeFrame: 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
measure: Rotavirus in Diarrheal Stool Samples
timeFrame: From Dose 1 until 2 months after dose 3 or until end of RV shedding
measure: Rotavirus Vaccine Strain Identification
timeFrame: From dose 1 until 2 months after dose 3 or until end of RV shedding
measure: Enteric Pathogens Identification
timeFrame: From Dose 1 until 2 months after dose 3 or until end of RV shedding
measure: Number of Subjects With the RV in Stool Samples
timeFrame: From Dose 1 until post Dose 3
Other outcomes:
Locations:
city: Attridgerville
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Coronationville
country: South Africa
facility: GSK Investigational Site
state: Gauteng
city: Garankuwa
country: South Africa
facility: GSK Investigational Site
state: North-West
city: Brits
country: South Africa
facility: GSK Investigational Site
city: Capital Park
country: South Africa
facility: GSK Investigational Site
city: Ga-Rankuwa
country: South Africa
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Buyse H, Vinals C, Karkada N, Han HH. The human rotavirus vaccine Rotarix in infants: an integrated analysis of safety and reactogenicity. Hum Vaccin Immunother. 2014;10(1):19-24. doi: 10.4161/hv.26476. Epub 2013 Oct 8.
citation: Steele AD, Madhi SA, Louw CE, Bos P, Tumbo JM, Werner CM, Bicer C, De Vos B, Delem A, Han HH. Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa. Pediatr Infect Dis J. 2011 Feb;30(2):125-30. doi: 10.1097/INF.0b013e3181f42db9.
citation: Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, Cheuvart B, Espinoza F, Gillard P, Innis BL, Cervantes Y, Linhares AC, Lopez P, Macias-Parra M, Ortega-Barria E, Richardson V, Rivera-Medina DM, Rivera L, Salinas B, Pavia-Ruz N, Salmeron J, Ruttimann R, Tinoco JC, Rubio P, Nunez E, Guerrero ML, Yarzabal JP, Damaso S, Tornieporth N, Saez-Llorens X, Vergara RF, Vesikari T, Bouckenooghe A, Clemens R, De Vos B, O'Ryan M; Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006 Jan 5;354(1):11-22. doi: 10.1056/NEJMoa052434.