Safety and Immunogenicity Study of the Tetravalent Rotavirus Vaccine

Phase I/II, Randomized, Double-blind, Placebo-controlled, Dosage Selection (10e5.5 or 10e6.25 FFU of Each Constituent Serotype Per 0.5 mL) Study to Evaluate the Safety, Tolerability, and Immunogenicity of a 3-dose Series of Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine [BRV-TV] Administered to Healthy Indian Infants

A double blind placebo controlled Phase I/II study to evaluate the safety and immunogenicity of the Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine [BRV-TV]in Indian infants. The study would be carried out in 90 healthy infants. Three doses of the rotavirus vaccine or placebo would be administered orally to each infant at 6-8, 10-12 and 14-16 weeks of age. The rotavirus vaccine would be administered at one of the two planned virus concentrations (10e5.5 or 10e6.25 FFU of each constituent serotype per 0.5 ml). Each administration of the vaccine/placebo would be preceded by oral administration of 2.0 mL of antacid.

Study Overview

• Status: Unknown
• Conditions: Rotavirus Gastroenteritis
• Intervention / Treatment: Other: Placebo; Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine; Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• India
  • Tamilnadu
    • Vellore, Tamilnadu, India, 632002
      • Recruiting
      • Christian Medical College
      • Contact: Gagandeep Kang, MD PhD; Phone Number: +914162282052; Email: gkang@cmcvellore.ac.in
      • Principal Investigator: Gagandeep Kang, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants 6-8 weeks of age at time of enrollment of either sex;
• Born after a gestational period of 36-42 weeks with birth weight ≥2 kg;
• Father, mother or other legally acceptable representative (guardian) properly informed about the study and having signed the informed consent form (ICF). In case of father, mother or other legally acceptable representative (guardian) being unable to read or write, having had the ICF explained to them in the presence of a study independent witness and the witness having signed the ICF;
• Parent or guardian available for the entire period of the study and reachable by study staff for post-vaccination follow-up.

Exclusion Criteria:

• History of congenital abdominal disorders, intussusception, or abdominal surgery;
• Known or suspected impairment of immunological function;
• Known hypersensitivity to any component of the rotavirus vaccine;
• Prior receipt of any rotavirus vaccine;
• Fever, with axillary temperature ≥38.1oC (≥100.5oF); measured by study staff.
• History of known rotavirus disease, chronic diarrhea, or failure to thrive;
• Baseline level of ALT or AST >2.5 times the upper limit of normal;
• Clinical evidence of active gastrointestinal illness (infants with GERD can participate in the study so long as this condition is well controlled with or without medication);
• Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days (infants on inhaled steroids may be permitted to participate in the study);
• Infants residing in a household with an immuno-compromised person (e.g., individuals with a congenital immunodeficiency, HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephrotic syndrome, organ or bone marrow transplantation, or those receiving immunosuppressive chemotherapy including long-term systemic corticosteroids);
• Infants suspected to be HIV, HBV or HCV positive from the available clinical history or born to mothers known to be HIV, HBV or HCV positive.
• Prior receipt of a blood transfusion or blood products, including immunoglobulins;
• Any infants who cannot be adequately followed for safety by a home visit;
• Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
• Parent/s or guardian of subject unable to maintain diary card

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: Vaccine - High dosage	Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine; Higher dosage of vaccine; Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine; Lower dosage of vaccine
Experimental: Vaccine - Lower dosage	Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine; Higher dosage of vaccine; Biological: Live Attenuated Tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus Vaccine; Lower dosage of vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The frequency, severity, and causality of Reactogenicity Events and other Adverse Events.	After each dose and upto 28 days after third dose

Secondary Outcome Measures

Outcome Measure	Time Frame
The Seroconversion rate, Sero-response rate and the GMT of serum IgA antibody against rotavirus.	After each dose and upto 28 days after third dose
The frequency and duration of post-vaccination shedding of vaccine rotavirus in stool samples	After each dose and upto 7 days after third dose

Collaborators and Investigators

• Sponsor: Shantha Biotechnics Limited
• Investigators: Study Director: Raman Rao, MD, Shantha Biotechnics Limited

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Anticipated): November 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 2, 2010
• First Posted (Estimate): February 3, 2010

Study Record Updates

• Last Update Posted (Estimate): October 4, 2010
• Last Update Submitted That Met QC Criteria: October 1, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: SBL/BRV-TV/Form1/PhI/2009/0100