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

Primary Purpose

Rotavirus Gastroenteritis

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V260
Placebo to V260
OPV
DTaP
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rotavirus Gastroenteritis

Eligibility Criteria

6 Weeks - 12 Weeks (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Placebo Comparator

    Experimental

    Placebo Comparator

    Arm Label

    V260 with staggered EPI

    Placebo with staggered EPI

    V260 with concomitant EPI

    Placebo with concomitant EPI

    Arm Description

    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

    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

    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

    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

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Full Information

    First Posted
    February 12, 2014
    Last Updated
    October 30, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02062385
    Brief Title
    Efficacy, Safety, and Immunogenicity of V260 in Healthy Chinese Infants (V260-024)
    Official Title
    A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Immunogenicity of V260 in Healthy Chinese Infants
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    May 30, 2014 (Actual)
    Primary Completion Date
    June 11, 2015 (Actual)
    Study Completion Date
    June 11, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rotavirus Gastroenteritis

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    4040 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    V260 with staggered EPI
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Placebo with staggered EPI
    Arm Type
    Placebo Comparator
    Arm Description
    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
    Arm Title
    V260 with concomitant EPI
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Placebo with concomitant EPI
    Arm Type
    Placebo Comparator
    Arm Description
    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
    Intervention Type
    Biological
    Intervention Name(s)
    V260
    Intervention Description
    V260 (RotaTeq™; live, oral, pentavalent rotavirus vaccine)
    Intervention Type
    Biological
    Intervention Name(s)
    Placebo to V260
    Intervention Description
    Placebo control
    Intervention Type
    Biological
    Intervention Name(s)
    OPV
    Intervention Description
    Oral poliovirus vaccine administered according to the standard of care
    Intervention Type
    Biological
    Intervention Name(s)
    DTaP
    Intervention Description
    Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care
    Primary Outcome Measure Information:
    Title
    Number of Participants With Any Severity of Rotavirus Gastroenteritis
    Description
    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.
    Time Frame
    From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months)
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Elevated Temperature
    Description
    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.
    Time Frame
    Up to 30 days after any dose of V260 or Placebo
    Title
    Percentage of Participants With Vomiting or Diarrhea
    Description
    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.
    Time Frame
    Up to 30 days after any dose of V260 or Placebo
    Title
    Percentage of Participants With Intussusception
    Description
    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.
    Time Frame
    Up to 15 months
    Title
    Number of Participants With Severe Rotavirus Gastroenteritis
    Description
    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.
    Time Frame
    From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months)
    Title
    Percentage of Participants Who Achieved Seroprotection Against Poliovirus Type 1, 2, or 3
    Description
    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.
    Time Frame
    Baseline and between 28 and 56 days after the third OPV vaccination
    Title
    Percentage of Participants With Any Adverse Event
    Description
    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.
    Time Frame
    Up to 30 days after any dose of V260 or Placebo
    Title
    Percentage of Participants Seropositive to Diphtheria, Pertussis, or Tetanus Antigens
    Description
    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.
    Time Frame
    Baseline and between 28 and 51 days after the third DTaP vaccination

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    6 Weeks
    Maximum Age & Unit of Time
    12 Weeks
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    28935470
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    30808567
    Citation
    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.
    Results Reference
    derived

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

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