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

Study Overview
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Brief Summary
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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.

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

Conditions
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Rotavirus Gastroenteritis

Intervention / Treatment
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* Biological: V260
* Biological: Placebo to V260
* Biological: OPV
* Biological: DTaP


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V260 with staggered EPI<br>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<br>* V260 (RotaTeq™; live, oral, pentavalent rotavirus vaccine)<br>Biological: OPV<br>* Oral poliovirus vaccine administered according to the standard of care<br>Biological: DTaP<br>* Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care<br>|
| Placebo Comparator: Placebo with staggered EPI<br>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<br>* Placebo control<br>Biological: OPV<br>* Oral poliovirus vaccine administered according to the standard of care<br>Biological: DTaP<br>* Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care<br>|
| Experimental: V260 with concomitant EPI<br>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<br>* V260 (RotaTeq™; live, oral, pentavalent rotavirus vaccine)<br>Biological: OPV<br>* Oral poliovirus vaccine administered according to the standard of care<br>Biological: DTaP<br>* Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care<br>|
| Placebo Comparator: Placebo with concomitant EPI<br>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<br>* Placebo control<br>Biological: OPV<br>* Oral poliovirus vaccine administered according to the standard of care<br>Biological: DTaP<br>* Diphtheria, Tetanus, Acellular Pertussis vaccine administered according to the standard of care<br>|

What is the study measuring?
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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 |