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

Infections, Rotavirus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00420745
• Other study ID #: 106481
• Status: Completed
• Phase: Phase 3
• Start date: January 25, 2007
• Est. completion date: March 25, 2008

Study information

• Verified date: November 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1009
• Est. completion date: March 25, 2008
• Est. primary completion date: March 1, 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 14 Weeks

Eligibility

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.

Related Conditions & MeSH terms

• Infections, Rotavirus
• Rotavirus Infections

Intervention

Biological:
• Rotarix™
Two-dose oral vaccination.
• Placebo
Two-dose oral administration

Locations

Country	Name	City	State
France	GSK Investigational Site	Bondy
France	GSK Investigational Site	Bordeaux
France	GSK Investigational Site	Caen
France	GSK Investigational Site	Clermont Ferrand
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Paris
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Mielec
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Wroclaw
Portugal	GSK Investigational Site	Amadora
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Lisboa
Portugal	GSK Investigational Site	Porto
Spain	GSK Investigational Site	Almería
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Bilbao
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Fuenlabrada (Madrid)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Malaga
Spain	GSK Investigational Site	Móstoles/Madrid
Spain	GSK Investigational Site	Valladolid

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

France,  Poland,  Portugal,  Spain, 

References & Publications (3)

Omenaca F et al. Immunogenicity of a rotavirus vaccine (RIX4414) in European pre-term infants with different gestational age. Abstract presented at the 27th annual ESPID meeting, Brussels, Belgium, 9-13 June 2009.

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, Sarlangue J, Szenborn L, Nogueira M, Suryakiran PV, Smolenov IV, Han HH; ROTA-054 Study Group. Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study. Pediatr Infect Dis J. 2012 May;31(5):487-93. doi: 10.1097/INF.0b013e3182490a2c. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects Reporting Any Serious Adverse Events (SAEs).	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.	From Day 0 up to 1 month after Dose 2 of Rotarix vaccine/Placebo
Secondary	Number of Subjects Reporting Unsolicited Adverse Events (AEs), According to Medical Dictionary for Regulatory Activities (MedDRA) Classification.	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.	Within 31 days after any Rotarix vaccine/Placebo dose.
Secondary	Number of Subjects for Whom Each Type of Solicited Symptom Was Reported.	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	Within 15 days after each Rotarix vaccine/Placebo dose.
Secondary	Number of Subjects for Whom Presence of Rotavirus (RV) Gastroenteritis (GE) Was Detected in Stools.	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.	From Dose 1 up to 1 month after Dose 2 of Rotarix vaccine/Placebo
Secondary	Seroconversion to Anti-rotavirus Immunoglobulin A (IgA) Antibody.	Number of subjects with anti-rotavirus IgA antibody concentration = 20 Units/milliliter (U/mL).	At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo
Secondary	Serum Anti-Rotavirus IgA Antibody Concentration.	Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals, calculated on all subjects.	At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo

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