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

• ClinicalTrials.gov Identifier: NCT02062385
• Recruitment Status: Completed
• First Posted: February 13, 2014
• Results First Posted: April 4, 2016
• Last Update Posted: November 27, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

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.

Condition or disease	Intervention/treatment	Phase
Rotavirus Gastroenteritis	Biological: V260; Biological: Placebo to V260; Biological: OPV; Biological: DTaP	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4040 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Immunogenicity of V260 in Healthy Chinese Infants
• Actual Study Start Date: May 30, 2014
• Actual Primary Completion Date: June 11, 2015
• Actual Study Completion Date: June 11, 2015

Arms and Interventions

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: Placebo to V260; Placebo control; 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
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: Placebo to V260; Placebo control; 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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Any Severity of Rotavirus Gastroenteritis [ Time Frame: From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months) ]
   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 :

1. Percentage of Participants With Elevated Temperature [ Time Frame: Up to 30 days after any dose of V260 or Placebo ]
   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.
2. Percentage of Participants With Vomiting or Diarrhea [ Time Frame: Up to 30 days after any dose of V260 or Placebo ]
   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.
3. Percentage of Participants With Intussusception [ Time Frame: Up to 15 months ]
   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.
4. Number of Participants With Severe Rotavirus Gastroenteritis [ Time Frame: From 14 days after the third dose of V260 or placebo through the first rotavirus season (up to 15 months) ]
   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.
5. Percentage of Participants Who Achieved Seroprotection Against Poliovirus Type 1, 2, or 3 [ Time Frame: Baseline and between 28 and 56 days after the third OPV vaccination ]
   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.
6. Percentage of Participants With Any Adverse Event [ Time Frame: Up to 30 days after any dose of V260 or Placebo ]
   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.
7. Percentage of Participants Seropositive to Diphtheria, Pertussis, or Tetanus Antigens [ Time Frame: Baseline and between 28 and 51 days after the third DTaP vaccination ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT02062385
• Other Study ID Numbers: V260-024
• First Posted: February 13, 2014
• Results First Posted: April 4, 2016
• Last Update Posted: November 27, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases