Efficacy, Safety, and Immunogenicity of V260 in Healthy Chinese Infants (V260-024)

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Immunogenicity of V260 in Healthy Chinese Infants

This study will assess the efficacy, safety, and immunogenicity of a 3-dose regimen of RotaTeq™ (V260) in healthy Chinese infants. Approximately 4040 participants at least 6 weeks and up to 12 weeks of age at the time of the first vaccination with V260 or placebo will be enrolled and randomized (1:1) to receive either V260 or placebo. Participants will also receive the routine China Expanded Program on Immunization (EPI) vaccines (oral poliovirus vaccine [OPV] and diphtheria, tetanus, and acellular pertussis vaccine [DTaP]) either staggered or concomitantly with V260 or placebo. All participants will be followed for efficacy and safety. Immune responses to OPV and DTaP will be evaluated in a subset of participants. The primary hypothesis of the study states that V260 will be efficacious in preventing any severity of rotavirus gastroenteritis as compared with placebo.

Study Overview

• Status: Completed
• Conditions: Rotavirus Gastroenteritis
• Intervention / Treatment: Biological: V260; Biological: OPV; Biological: DTaP; Biological: Placebo to V260

• Study Type: Interventional
• Enrollment (Actual): 4040
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants at least 6 weeks (42 days) and up to 12 weeks (84 days) of age at the time of the first study vaccination
• Parent/legal guardian agrees to participate by giving written informed consent and is willing and able to comply with study requirements

Exclusion Criteria:

• History of congenital abdominal disorders, prior rotavirus gastroenteritis, chronic diarrhea, failure to thrive, or abdominal surgery
• History of intussusception
• Impairment of immunological function, including Severe Combined Immunodeficiency (SCID)
• Acute disease, severe chronic disease, or chronic disease during the acute period
• Uncontrolled epilepsy, encephalopathy, seizure, or other progressive neurological disease
• Hypersensitivity to any component of the rotavirus vaccine, OPV, or DTaP
• Prior receipt of any rotavirus vaccine
• Fever, with an axillary temperature >=37.5 °C (or equivalent) within 24 hours before study vaccination (study vaccination can be deferred until complete resolution of febrile illness)
• Clinical evidence of active gastrointestinal illness
• Received intramuscular, oral, or intravenous corticosteroid treatment since birth (topical, ophthalmic, and inhaled steroids are permitted)
• Resides in a household with an immunocompromised person
• Receipt of a blood transfusion or blood products, including immunoglobulins
• Participation in another interventional study within 14 days before the first study vaccination or during the study
• Receipt of an investigational or non-registered product other than the study vaccine within 30 days before the first study vaccination or during the study
• For participants in immunogenicity arms: inability to obtain a blood specimen at randomization visit (note: the visit may be rescheduled so that a baseline specimen may be obtained); history of polio, diphtheria, tetanus, or pertussis disease; previous vaccination against diphtheria, tetanus, pertussis, or poliomyelitis
• Any condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V260 with staggered EPI; V260 administered as a 2 mL oral solution at age ~2, 3, and 4 months, and staggered China Expanded Program on Immunizations (EPI) as follows: Oral poliovirus vaccine (OPV) administered as a 1 g oral solution at age ~2.5, 3.5, and 4.5 months, and diphtheria, tetanus, acellular pertussis vaccine (DTaP) administered as a 0.5 mL intramuscular injection at age ~3.5, 4.5, and 5.5 months	Biological: V260; V260 (RotaTeq™; live, oral, pentavalent rotavirus vaccine); Biological: OPV; Oral poliovirus vaccine administered according to the standard of care; Biological: DTaP; Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care
Placebo Comparator: Placebo with staggered EPI; Placebo administered as a 2 mL oral solution at age ~2, 3, and 4 months, and staggered EPI as follows: OPV administered as a 1 g oral solution at age ~2.5, 3.5, and 4.5 months, and DTaP administered as a 0.5 mL intramuscular injection at age ~3.5, 4.5, and 5.5 months	Biological: OPV; Oral poliovirus vaccine administered according to the standard of care; Biological: DTaP; Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care; Biological: Placebo to V260; Placebo control
Experimental: V260 with concomitant EPI; V260 administered as a 2 mL oral solution at age ~2, 3, and 4 months, and concomitant EPI as follows: OPV administered as a 1 g oral solution at age ~2, 3, and 4 months and DTaP administered as a 0.5 mL intramuscular injection at age ~3, 4, and 5 months	Biological: V260; V260 (RotaTeq™; live, oral, pentavalent rotavirus vaccine); Biological: OPV; Oral poliovirus vaccine administered according to the standard of care; Biological: DTaP; Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care
Placebo Comparator: Placebo with concomitant EPI; Placebo administered as a 2 mL oral solution at age ~2, 3, and 4 months, and concomitant EPI as follows: OPV administered as a 1 g oral solution at age ~2, 3, and 4 months and DTaP administered as a 0.5 mL intramuscular injection at age ~3, 4, and 5 months	Biological: OPV; Oral poliovirus vaccine administered according to the standard of care; Biological: DTaP; Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care; Biological: Placebo to V260; Placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Severity of Rotavirus Gastroenteritis	The number of participants with rotavirus gastroenteritis (RVGE) caused by naturally-occurring wild-type rotavirus (regardless of serotype or disease severity) was assessed. The case definition of RVGE included 1) 3 or more watery or looser-than-normal stools within a 24-hour period and/or forceful vomiting, and 2) naturally-occurring wild-type rotavirus must be detected in a stool specimen taken within 7 days after the onset of symptoms.	From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Elevated Temperature	Elevated temperature (temperature >=37.5°C axillary or equivalent) was noted by the guardian and recorded on the Vaccination Report Card during Day 1 to Day 14 after each dose of vaccination. Elevated temperature reported by the guardian was also collected as an adverse event (pyrexia) during Day 15 to Day 30 after each dose of vaccination. The percentage of participants with axillary temperature >=37.5 °C or an adverse event of pyrexia was assessed.	Up to 30 days after any dose of V260 or Placebo
Percentage of Participants With Vomiting or Diarrhea	Episodes of vomiting and diarrhea were noted by the guardian and recorded on the Vaccination Record Card during Day 1 to Day 14 after each dose of vaccination. Vomiting and diarrhea reported by the guardian were also collected as an adverse event during Day 15 to Day 30 after any dose of vaccination. The percentage of participants with an episode or an adverse event of vomiting or diarrhea was assessed.	Up to 30 days after any dose of V260 or Placebo
Percentage of Participants With Intussusception	Episodes of intussusception were collected from the time of written consent until the end of study. The percentage of participants with an episode of intussusception was assessed.	Up to 15 months
Number of Participants With Severe Rotavirus Gastroenteritis	The number of participants with severe rotavirus gastroenteritis (RVGE) caused by naturally-occurring wild-type rotavirus (regardless of serotype or disease severity) was assessed. The case definition of RVGE included 1) 3 or more watery or looser-than-normal stools within a 24-hour period and/or forceful vomiting, and 2) naturally-occurring wild-type rotavirus must be detected in a stool specimen taken within 7 days after the onset of symptoms. Severe RVGE was defined as >=11 on the Vesikari Scoring System, a composite of the seven parameters related to symptoms and treatment with an overall range from 0 to 20.	From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months)
Percentage of Participants Who Achieved Seroprotection Against Poliovirus Type 1, 2, or 3	The percentage of participants who achieved seroprotection against poliovirus Type 1, 2, or 3 was assessed. Seroprotection was defined as a neutralizing antibody titer >=1:8. This outcome was evaluated only in participants receiving concomitant administration of V260 and OPV.	Baseline and between 28 and 56 days after the third OPV vaccination
Percentage of Participants With Any Adverse Event	An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the sponsor's product, is also an adverse event.	Up to 30 days after any dose of V260 or Placebo
Percentage of Participants Seropositive to Diphtheria, Pertussis, or Tetanus Antigens	The percentage of participants seropositive to diphtheria, pertussis, or tetanus antigens was assessed. Seropositive was defined as the following: 1) anti-diphtheria antibody titers >=0.1 International Units (IU)/mL, 2) anti-tetanus antibody titers >=0.1 IU/mL, 3) antipertussis toxin antibody titers >=20 Enzyme-linked Immunosorbent Assay (ELISA) Units (EU)/mL, 4) anti-pertussis filamentous hemagglutinin (FHA) antibody titers >=20 EU/mL. This outcome was evaluated only in participants receiving concomitant administration of V260 and EPI.	Baseline and between 28 and 51 days after the third DTaP vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Mo Z, Mo Y, Li M, Tao J, Yang X, Kong J, Wei D, Fu B, Liao X, Chu J, Qiu Y, Hille DA, Nelson M, Kaplan SS. Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial. Vaccine. 2017 Oct 13;35(43):5897-5904. doi: 10.1016/j.vaccine.2017.08.081. Epub 2017 Sep 19.
• Mo Z, Ma X, Luo P, Mo Y, Kaplan SS, Shou Q, Zheng M, Hille DA, Arnold BA; V260-024 Study Group; Liao X. Immunogenicity of pentavalent rotavirus vaccine in Chinese infants. Vaccine. 2019 Mar 22;37(13):1836-1843. doi: 10.1016/j.vaccine.2019.02.018. Epub 2019 Feb 23.

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2014
• Primary Completion (Actual): June 11, 2015
• Study Completion (Actual): June 11, 2015

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 13, 2014

Study Record Updates

• Last Update Posted (Actual): November 27, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: V260-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf