Rotavirus Efficacy and Safety Trial (REST)(V260-006)

Safety and Efficacy of Pentavalent (G1, G2, G3, G4 , and P1) Human-Bovine Reassortant Rotavirus Vaccine in Healthy Infants

This study was designed to evaluate the safety of the investigational rotavirus vaccine and the efficacy to prevent rotavirus gastroenteritis.

Study Overview

• Status: Completed
• Conditions: Rotavirus Infections
• Intervention / Treatment: Biological: Rotateq™; Biological: Comparator: Placebo

• Study Type: Interventional
• Enrollment (Actual): 69274
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants

Exclusion Criteria:

• None Specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Biological: Comparator: Placebo; 3 doses of 2.0 mL Placebo to RotaTeq administered orally. Dose 1 will be given at study entry, Dose 2 will be given 4-10 weeks after Dose 1, Dose 3 will be given 4-10 weeks after Dose 2.
Experimental: 1; RotaTeq	Biological: Rotateq™; 3 doses of 2.0 mL RotaTeq administered orally. Dose 1 will be given at study entry, Dose 2 will be given 4-10 weeks after Dose 1, Dose 3 will be given 4-10 weeks after Dose 2.; Other Names: V260

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo	Number of participants with confirmed intussusception within 42 days after each vaccination with RotaTeq™/placebo.	Within 42 days following any dose of RotaTeq™/placebo
Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination	Rotavirus gastroenteritis cases consist of all participants with one or more episodes classified as positive. Multiple positive episodes for one participant are counted as a single case.	At least 14 days following the 3rd vaccination through the first full rotavirus season

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus	Number of participants with a 3-fold rise or greater in G1 Serum neutralizing antibody (SNA) responses against rotavirus from baseline to postdose 3.	14 days following the 3rd vaccination
Occurrence of Hospital Admissions and Visits to Emergency Departments (or the Equivalent at International Sites) for Rotavirus Disease Associated With Serotypes G1, G2, G3, or G4	Health Outcomes Substudy - Occurrence of hospital admissions and emergency department visits for episode(s) of rotavirus gastroenteritis associated with serotypes G1, G2, G3, or G4 by treatment group. Occurrence was expressed as the annual number of events per 1000 person-years.	At least 14 days following the 3rd vaccination
Efficacy of a 3-dose Regimen of RotaTeq™ Against Moderate-to-severe Rotavirus Disease (Clinical Score >8) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose.	Number of participants with rotavirus gastroenteritis whose clinical score was >8 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].	At least 14 days following the 3rd vaccination through the first rotavirus season
Efficacy of a 3-dose Regimen of RotaTeq™ Against Severe Rotavirus Disease (Clinical Score > 16) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose	Number of participants with rotavirus gastroenteritis whose clinical score was >16 for the first episode and for the worst episode. Scores evaluated the intensity and duration of diarrhea, vomiting, fever, and behavioral symptoms. The total score for an episode is equal to the sum of the scores for each of the symptoms [range: total score 0 (best) to 24 (worst)].	At least 14 days following the 3rd vaccination through the first rotavirus season
Seroprotection/Seroconversion for Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus, & Polio Types 1,2,& 3 Who Received COMVAX™, INFANRIX™, IPOL™ & PREVNAR™ Concomitantly With RotaTeq™ Versus Placebo	The number of participants who achieved seroprotection/seroconversion to hepatitis B, Haemophilus influenzae type b, diphtheria, tetanus, & polio types 1, 2, & 3, per established criteria.	42 days following third dose
Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin	Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin. Antibody titers were measured with an indirect, non-competitive, enzyme immunoassay (EIA).	42 days following third dose
Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F	Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Serum antibody titers to type-specific pneumococcal polysaccharides were determined by an EIA.	42 days following third dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, Dallas MJ, Heyse JF, Goveia MG, Black SB, Shinefield HR, Christie CD, Ylitalo S, Itzler RF, Coia ML, Onorato MT, Adeyi BA, Marshall GS, Gothefors L, Campens D, Karvonen A, Watt JP, O'Brien KL, DiNubile MJ, Clark HF, Boslego JW, Offit PA, Heaton PM; Rotavirus Efficacy and Safety Trial (REST) Study Team. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med. 2006 Jan 5;354(1):23-33. doi: 10.1056/NEJMoa052664.
• Itzler R, Koch G, Matson DO, Gothefors L, Van Damme P, Dinubile MJ, Heaton PM. Robustness of the healthcare utilization results from the Rotavirus Efficacy and Safety Trial (REST) evaluating the human-bovine (WC3) reassortant pentavalent rotavirus vaccine (RV5). BMC Pediatr. 2010 Jun 11;10:42. doi: 10.1186/1471-2431-10-42.

Study record dates

Study Major Dates

• Study Start: January 1, 2001
• Primary Completion (Actual): October 1, 2004
• Study Completion (Actual): October 1, 2004

Study Registration Dates

• First Submitted: August 25, 2004
• First Submitted That Met QC Criteria: August 26, 2004
• First Posted (Estimate): August 27, 2004

Study Record Updates

• Last Update Posted (Estimate): October 5, 2015
• Last Update Submitted That Met QC Criteria: September 18, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections
• Other Study ID Numbers: V260-006; 2004_012