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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02062385
• Collaborator: (none)
• Enrollment: 4,040
• Arms: 4
• Actual Duration (Months): 12.4

Study Details

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
• 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: Jun 11, 2015
• Actual Study Completion Date: Jun 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 [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 [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 [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 [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 [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 [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 [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 [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

Criteria

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

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

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02062385
• Other Study ID Numbers: V260-024
• First Posted: Feb 13, 2014
• Last Update Posted: Nov 27, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Gastroenteritis

Study Results

Participant Flow

Recruitment Details	A total of 4173 participants were screened, 4040 were randomized, and 4037 received at least one dose of study vaccination.

Arm/Group Title	V260 With Staggered EPI	Placebo With Staggered EPI	V260 With Concomitant EPI	Placebo With Concomitant EPI
Arm/Group Description	V260 administered as a 2 mL oral solution at age ~2, 3, and 4 months, and staggered China Expanded Program on Immunization (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.
Period Title: Overall Study
STARTED	1620	1620	400	400
Received Vaccination 1	1618	1619	400	400
Received Vaccination 2	1554	1566	392	393
Received Vaccination 3	1543	1554	389	392
COMPLETED	1542	1555	388	391
NOT COMPLETED	78	65	12	9

Baseline Characteristics

Arm/Group Title	V260 With Staggered EPI	Placebo With Staggered EPI	V260 With Concomitant EPI	Placebo With Concomitant EPI	Total
Arm/Group Description	V260 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.	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.	Total of all reporting groups
Overall Participants	1620	1620	400	400	4040
Age (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	57.5 (10.0)	57.2 (9.7)	68.3 (5.7)	68.5 (5.7)	59.5 (10.2)
Sex: Female, Male (Count of Participants)
Female	806 49.8%	775 47.8%	185 46.3%	183 45.8%	1949 48.2%
Male	814 50.2%	845 52.2%	215 53.8%	217 54.3%	2091 51.8%

Outcome Measures

1. Primary Outcome

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)

Outcome Measure Data

Analysis Population Description

Participants who were vaccinated in either the staggered EPI or concomitant EPI groups, were not protocol violators, and were classified as evaluable for RVGE according to the per-protocol case definition.

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	1927	1937
Number [Participants]	34 2.1%	109 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	V260 With Staggered or Concomitant EPI, Placebo With Staggered or Concomitant EPI
	Comments	V260 will be considered efficacious if the lower bound of the two-sided confidence interval for efficacy is >0% at the final analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Clopper-Pearson
	Comments	To calculate the confidence interval and associated p-value, an exact conditional method based on a Poisson distribution was used.
Method of Estimation	Estimation Parameter	1 - (Incidence V260 / Incidence Placebo)
	Estimated Value	69.3
	Confidence Interval	(2-Sided) 95%; 54.5 to 79.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All Subjects as Treated with follow-up specific to the endpoint

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	2015	2019
Number [Percentage of participants]	21.84 1.3%	22.83 1.4%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All Subjects as Treated with safety follow-up

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	2015	2019
Vomiting	2.68 0.2%	3.52 0.2%
Diarrhea	20.15 1.2%	20.11 1.2%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All Subjects as Treated with safety follow-up

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	2015	2019
Number [Percentage of participants]	0.10 0%	0.00 0%

5. Secondary Outcome

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)

Outcome Measure Data

Analysis Population Description

Participants who were vaccinated in either the staggered EPI or concomitant EPI groups, were not protocol violators, and were classified as evaluable for RVGE according to the per-protocol case definition.

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	1926	1937
Number [Participants]	11 0.7%	52 3.2%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the concomitant EPI groups who receive their scheduled doses of OPV without intervening disease specific to the antigen before the blood sample collection postdose 3, adhere to the guidelines for administration of vaccine, and have valid values available for analysis within specified day ranges.

Arm/Group Title	V260 With Concomitant EPI	Placebo With Concomitant EPI
Arm/Group 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.	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.
Measure Participants	187	192
Poliovirus Type 1: Baseline, n=186, 190	44.09 2.7%	38.95 2.4%
Poliovirus Type 1: Post OPV #3, n=187, 192	98.93 6.1%	100.00 6.2%
Poliovirus Type 2: Baseline, n=186, 190	44.09 2.7%	41.58 2.6%
Poliovirus Type 2: Post OPV #3, n=187, 192	100.00 6.2%	100.00 6.2%
Poliovirus Type 3: Baseline, n=186, 190	25.27 1.6%	21.05 1.3%
Poliovirus Type 3: Post OPV #3, n=187, 192	98.93 6.1%	98.96 6.1%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All Subjects as Treated with safety follow-up

Arm/Group Title	V260 With Staggered or Concomitant EPI	Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
Measure Participants	2015	2019
Number [Percentage of participants]	53.5 3.3%	53.3 3.3%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the concomitant EPI groups who receive their scheduled doses of DTaP without intervening disease specific to the antigen before the blood sample collection postdose 3, adhere to the guidelines for administration of vaccine, and have valid values available for analysis within specified day ranges.

Arm/Group Title	V260 With Concomitant EPI	Placebo With Concomitant EPI
Arm/Group 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.	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.
Measure Participants	187	194
Diphtheria: Baseline, n=181, 186	3.31 0.2%	2.69 0.2%
Diphtheria: Post DTaP #3, n=187, 194	99.47 6.1%	99.48 6.1%
Pertussis FHA: Baseline, n=181, 186	0.00 0%	0.00 0%
Pertussis FHA: Post DTaP #3, n=187, 194	44.92 2.8%	43.81 2.7%
Pertussis Toxin: Baseline, n=181, 186	1.66 0.1%	1.08 0.1%
Pertussis Toxin, Post DTaP #3, n=187, 194	95.19 5.9%	94.33 5.8%
Tetanus: Baseline, n=181, 186	12.15 0.8%	12.37 0.8%
Tetanus: Post DTaP #3, n=187, 194	100.00 6.2%	100.00 6.2%

Adverse Events

Time Frame	All Adverse Events: up to 30 days after any V260 or placebo vaccination; Serious Adverse Events: from the time of written consent until the end of the study (up to 15 months)
Adverse Event Reporting Description	The at-risk population was All Subjects as Treated
Arm/Group Title	V260 With Staggered or Concomitant EPI		Placebo With Staggered or Concomitant EPI
Arm/Group Description	V260 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 OR 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 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 OR 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.
All Cause Mortality
	V260 With Staggered or Concomitant EPI		Placebo With Staggered or Concomitant EPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	V260 With Staggered or Concomitant EPI		Placebo With Staggered or Concomitant EPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	339/2015 (16.8%)		338/2019 (16.7%)
Blood and lymphatic system disorders
Agranulocytosis	1/2015 (0%)	1	0/2019 (0%)	0
Anaemia	1/2015 (0%)	1	1/2019 (0%)	1
Granulocytopenia	1/2015 (0%)	1	0/2019 (0%)	0
Cardiac disorders
Cardiomyopathy	1/2015 (0%)	1	1/2019 (0%)	1
Congenital, familial and genetic disorders
Developmental hip dysplasia	1/2015 (0%)	1	0/2019 (0%)	0
Talipes	0/2015 (0%)	0	1/2019 (0%)	1
Thalassaemia	0/2015 (0%)	0	1/2019 (0%)	1
Thalassaemia beta	1/2015 (0%)	1	0/2019 (0%)	0
Ventricular septal defect	1/2015 (0%)	1	0/2019 (0%)	0
Eye disorders
Cataract	1/2015 (0%)	1	0/2019 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/2015 (0%)	1	9/2019 (0.4%)	9
Dyspepsia	0/2015 (0%)	0	1/2019 (0%)	1
Enteritis	47/2015 (2.3%)	52	41/2019 (2%)	42
Functional gastrointestinal disorder	2/2015 (0.1%)	2	2/2019 (0.1%)	2
Gastrointestinal disorder	0/2015 (0%)	0	1/2019 (0%)	1
Incarcerated inguinal hernia	0/2015 (0%)	0	1/2019 (0%)	1
Intestinal obstruction	1/2015 (0%)	1	6/2019 (0.3%)	6
Intussusception	2/2015 (0.1%)	2	0/2019 (0%)	0
General disorders
Developmental delay	1/2015 (0%)	1	0/2019 (0%)	0
Hepatobiliary disorders
Hepatic function abnormal	0/2015 (0%)	0	1/2019 (0%)	1
Immune system disorders
Transient hypogammaglobulinaemia of infancy	2/2015 (0.1%)	2	1/2019 (0%)	1
Infections and infestations
Acute tonsillitis	9/2015 (0.4%)	9	5/2019 (0.2%)	5
Bronchiolitis	2/2015 (0.1%)	2	1/2019 (0%)	1
Bronchitis	84/2015 (4.2%)	89	101/2019 (5%)	108
Bronchopneumonia	129/2015 (6.4%)	144	141/2019 (7%)	158
Candida infection	0/2015 (0%)	0	3/2019 (0.1%)	3
Conjunctivitis	1/2015 (0%)	1	0/2019 (0%)	0
Cytomegalovirus infection	1/2015 (0%)	1	0/2019 (0%)	0
Diarrhoea infectious	20/2015 (1%)	20	21/2019 (1%)	22
Exanthema subitum	1/2015 (0%)	1	1/2019 (0%)	1
Gastroenteritis	3/2015 (0.1%)	3	3/2019 (0.1%)	3
Gastroenteritis adenovirus	0/2015 (0%)	0	1/2019 (0%)	1
Gastroenteritis bacterial	1/2015 (0%)	1	1/2019 (0%)	1
Gastroenteritis rotavirus	7/2015 (0.3%)	7	24/2019 (1.2%)	24
Gastroenteritis shigella	0/2015 (0%)	0	1/2019 (0%)	1
Gingivitis	0/2015 (0%)	0	1/2019 (0%)	1
Hand-foot-and-mouth disease	19/2015 (0.9%)	19	10/2019 (0.5%)	10
Herpangina	13/2015 (0.6%)	13	2/2019 (0.1%)	2
Herpes virus infection	0/2015 (0%)	0	1/2019 (0%)	1
Infection	1/2015 (0%)	1	0/2019 (0%)	0
Omphalitis	1/2015 (0%)	1	0/2019 (0%)	0
Oral candidiasis	0/2015 (0%)	0	1/2019 (0%)	1
Oral herpes	2/2015 (0.1%)	2	3/2019 (0.1%)	3
Oral infection	0/2015 (0%)	0	1/2019 (0%)	1
Otitis media	0/2015 (0%)	0	1/2019 (0%)	1
Pharyngitis	21/2015 (1%)	21	23/2019 (1.1%)	23
Pharyngitis bacterial	2/2015 (0.1%)	2	5/2019 (0.2%)	5
Pneumonia	30/2015 (1.5%)	34	14/2019 (0.7%)	14
Sepsis	1/2015 (0%)	1	1/2019 (0%)	1
Sinusitis	0/2015 (0%)	0	1/2019 (0%)	1
Tonsillitis	1/2015 (0%)	1	0/2019 (0%)	0
Tonsillitis bacterial	3/2015 (0.1%)	3	3/2019 (0.1%)	3
Toxoplasmosis	0/2015 (0%)	0	1/2019 (0%)	1
Upper respiratory tract infection	16/2015 (0.8%)	16	18/2019 (0.9%)	19
Injury, poisoning and procedural complications
Burns second degree	0/2015 (0%)	0	1/2019 (0%)	1
Eye contusion	0/2015 (0%)	0	1/2019 (0%)	1
Metabolism and nutrition disorders
Hypomagnesaemia	1/2015 (0%)	1	0/2019 (0%)	0
Malnutrition	0/2015 (0%)	0	1/2019 (0%)	1
Musculoskeletal and connective tissue disorders
Rickets	1/2015 (0%)	1	0/2019 (0%)	0
Nervous system disorders
Central nervous system lesion	1/2015 (0%)	1	0/2019 (0%)	0
Epilepsy	1/2015 (0%)	1	0/2019 (0%)	0
Febrile convulsion	0/2015 (0%)	0	3/2019 (0.1%)	3
Respiratory, thoracic and mediastinal disorders
Asthma	17/2015 (0.8%)	17	9/2019 (0.4%)	9
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/2015 (0%)	0	1/2019 (0%)	1
Dermatitis diaper	0/2015 (0%)	0	1/2019 (0%)	1
Urticaria	2/2015 (0.1%)	2	0/2019 (0%)	0
Other (Not Including Serious) Adverse Events
	V260 With Staggered or Concomitant EPI		Placebo With Staggered or Concomitant EPI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	938/2015 (46.6%)		931/2019 (46.1%)
Gastrointestinal disorders
Diarrhoea	406/2015 (20.1%)	487	406/2019 (20.1%)	504
General disorders
Pyrexia	414/2015 (20.5%)	492	419/2019 (20.8%)	481
Infections and infestations
Nasopharyngitis	228/2015 (11.3%)	248	233/2019 (11.5%)	268
Upper respiratory tract infection	91/2015 (4.5%)	98	103/2019 (5.1%)	114
Respiratory, thoracic and mediastinal disorders
Cough	115/2015 (5.7%)	133	92/2019 (4.6%)	109

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.