To Assess Safety, Reactogenicity & Immunogenicity of 2 Doses of GSK's Oral Human Rotavirus Vaccine in Pre-Term Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00420745
First received: January 9, 2007
Last updated: June 12, 2014
Last verified: March 2011
  Purpose

This study is planned to evaluate the safety (in terms of occurrence of any serious adverse events), reactogenicity (any side effects) and immunogenicity (ability of the vaccine to develop antibodies that fight infection) of the HRV vaccine when used in pre-term infants aged between 6 and 14 weeks at the time of the first dose in Portugal, France and Poland and in pre-term infants aged between 6 and 12 weeks at the time of first dose in Spain. The study will be performed in four European countries (France, Poland, Spain, and Portugal). 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
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Phase IIIb, Double Blind, Randomised, Placebo-Controlled, Multi-Country/Centre, Study to Assess Safety, Reactogenicity & Immunogenicity of 2 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine in Pre-Term Infants

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting Any Serious Adverse Events (SAEs). [ Time Frame: From Day 0 up to 1 month after Dose 2 of Rotarix vaccine/Placebo ] [ Designated as safety issue: No ]

    An 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.



Secondary Outcome Measures:
  • Number of Subjects Reporting Unsolicited Adverse Events (AEs), According to Medical Dictionary for Regulatory Activities (MedDRA) Classification. [ Time Frame: Within 31 days after any Rotarix vaccine/Placebo dose. ] [ Designated as safety issue: No ]
    An AE is 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.

  • Number of Subjects for Whom Each Type of Solicited Symptom Was Reported. [ Time Frame: Within 15 days after each Rotarix vaccine/Placebo dose. ] [ Designated as safety issue: No ]
    Solicited symptoms included Diarrhea (3 or more looser than normal stools/day), Fever (axillary temperature ≥ 37.5 degrees Celsius (°C)), Irritability, Loss of appetite, and Vomiting

  • Number of Subjects for Whom Presence of Rotavirus (RV) Gastroenteritis (GE) Was Detected in Stools. [ Time Frame: From Dose 1 up to 1 month after Dose 2 of Rotarix vaccine/Placebo ] [ Designated as safety issue: No ]
    Gastroenteritis (GE): diarrhoea with or without vomiting. Rotavirus (RV) GE: A GE episode was a RV GE if a stool sample taken during or not later than 7 days after the episode was RV positive by Enzyme Linked Immunosorbent Assay.

  • Seroconversion to Anti-rotavirus Immunoglobulin A (IgA) Antibody. [ Time Frame: At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo ] [ Designated as safety issue: No ]
    Number of subjects with anti-rotavirus IgA antibody concentration ≥ 20 Units/milliliter (U/mL).

  • Serum Anti-Rotavirus IgA Antibody Concentration. [ Time Frame: At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo ] [ Designated as safety issue: No ]
    Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals, calculated on all subjects.


Enrollment: 1009
Study Start Date: January 2007
Study Completion Date: March 2008
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotarix Group
All subjects received 2 oral doses of Rotarix vaccine, 1 dose at Day 0 and 1 dose at Month 1 or 2 depending on the country.
Biological: Rotarix™
Two-dose oral vaccination.
Placebo Comparator: Placebo Group
All subjects received 2 oral doses of placebo, 1 dose at Day 0 and 1 dose at Month 1 or 2 depending on the country.
Biological: Placebo
Two-dose oral administration

Detailed Description:

This is a Phase 3b study.

Each study group is further stratified into two sub-groups depending on the gestational age at birth of the subject:

  • Stratum I: very pre-term infants, born after a gestational period of 27-30 weeks (189-216 days) (20% of enrolment).
  • Stratum II: mild pre-term infants born after a gestational period of 31-36 weeks (217-258 days) (80% of enrolment).

The study will be conducted in a double-blind manner with respect to the HRV vaccine and placebo. The study will not be blinded with respect to the type of concomitantly administered routine infant vaccination.

In accordance with the local National Plan of Immunisation schedule in each of the respective participating countries, GSK Biologicals' Infanrix Hexa™ (DTPa-HBV-IPV/Hib), Infanrix Quinta™ (DTPa-IPV-Hib), Infanrix™+IPV+Hib (DTPa+IPV+Hib) and/or Engerix-B™ (HBV) will be co-administered (at a maximum interval of two days from each other) with each HRV vaccine or placebo dose.

Hepatitis B and Bacille Calmette-Guérin vaccines (BCG) at birth are allowed if included in the local National Plan of Immunisation schedule in participating countries.

At the discretion of the investigator the following vaccines may be administered during each subject's study participation:

  • Vaccine against Streptococcus pneumoniae (Prevenar®) in France and Spain (concomitantly with HRV vaccine/Placebo).
  • Vaccine against Neisseria meningitidis (Neis Vacc C®) is allowed if there is at least 14-days interval with respect to the administration of the HRV vaccine/Placebo.
  Eligibility

Ages Eligible for Study:   6 Weeks to 14 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  • Healthy male or female infant between, and including, 6 and 14 weeks (42 - 104 days) of age at the time of first study vaccination in Portugal, France and Poland. A male or female infant between, and including, 6 and 12 weeks of age at the time of first study vaccination in Spain.
  • Medically stable pre-term infants, born within a gestational period of 27 -36 weeks.
  • Written informed consent obtained from the parent or guardian of the subject.
  • Planned to be discharged from hospital's neonatal stay on or before the day of the first HRV vaccine/Placebo administration.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the HRV vaccine within 30 days preceding the first dose of HRV vaccine, or planned use during the study period.
  • Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
  • Planned administration/ administration of a vaccines not foreseen by the study protocol from birth till study end.
  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
  • Any clinically significant history of chronic gastrointestinal disease.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
  • Major congenital defects or serious chronic illness (subjects with severe broncho-pulmonary dysplasia requiring persistent oxygen-therapy will be excluded).
  • History of any neurologic disorders or seizures. Grade I and II intra-ventricular bleeding are allowed.
  • Acute disease at the time of enrolment.
  • Administration of immunoglobulins, and/or any blood products within one month (30 days) preceding the first dose of study vaccines or planned administration during the study period. Monoclonal anti-RSV therapy/prophylaxis and recombinant erythropoietin are allowed.
  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: NCT00420745

Locations
France
GSK Investigational Site
Bondy, France, 93140
GSK Investigational Site
Bordeaux, France, 33076
GSK Investigational Site
Caen, France, 14033
GSK Investigational Site
Clermont Ferrand, France, 63058
GSK Investigational Site
Lille, France, 59037
GSK Investigational Site
Lyon, France, 69437
GSK Investigational Site
Marseille, France, 13915
GSK Investigational Site
Paris, France, 75014
Poland
GSK Investigational Site
Bydgoszcz, Poland, 85-021
GSK Investigational Site
Debica, Poland, 39-200
GSK Investigational Site
Krakow, Poland, 31-503
GSK Investigational Site
Lodz, Poland, 91-347
GSK Investigational Site
Mielec, Poland, 39-300
GSK Investigational Site
Poznan, Poland, 61-709
GSK Investigational Site
Siemianowice Slaskie, Poland, 41-103
GSK Investigational Site
Wroclaw, Poland, 50345
Portugal
GSK Investigational Site
Amadora, Portugal, 2720-276 Amadora
GSK Investigational Site
Lisboa, Portugal, 1069-089
GSK Investigational Site
Lisboa, Portugal, 1449-005 Lisboa
GSK Investigational Site
Lisboa, Portugal, 1169-045 Lisboa
GSK Investigational Site
Porto, Portugal, 4050-371 PORTO
Spain
GSK Investigational Site
Almería, Spain, 04009
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Bilbao, Spain, 48013
GSK Investigational Site
Burgos, Spain, 09005
GSK Investigational Site
Fuenlabrada (Madrid), Spain, 28942
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Madrid, Spain, 28047
GSK Investigational Site
Malaga, Spain, 29010
GSK Investigational Site
Móstoles/Madrid, Spain, 28935
GSK Investigational Site
Valladolid, Spain, 47010
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Omenaca F et al. Safety, Reactogenicity and Immunogenicity of RIX4414 Live Attenuated Human Rotavirus Vaccine in Pre-Term Infants. Abstract presented at the ICAAC/IDSA Joint Meeting, Washington DC, US, 25-28 October 2008.
Omenaca F et al. (2012) Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European infants: a randomized phase IIIb study. Pediatr Infect Dis J. 31(5):487-493.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00420745     History of Changes
Other Study ID Numbers: 106481
Study First Received: January 9, 2007
Results First Received: March 13, 2009
Last Updated: June 12, 2014
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Rotavirus Infections
Reoviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 28, 2014