T2-ABMG: A Study to Evaluate Safety and Immunogenicity of tOPV in 1 to 5 Years and at 6 Weeks of Age

• Sponsor: Fidec Corporation (Other)
• Overall Status: Completed
• CT.gov ID: NCT02580201
• Collaborator: Bill and Melinda Gates Foundation (Other)
• Enrollment: 154
• Arm: 1
• Duration (Months): 9.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety (serious adverse events [SAEs]), and severe adverse events [AEs] (grade 3 according to CTCAE 4.03) after one dose of SABIN tOPV in 1-5 year-old children and three doses of SABIN tOPV in 6 week-old infants, and immunogenicity (seroprotection rates for all 3 serotypes) 28 days after three doses of SABIN tOPV in vaccine-naïve infants.

Condition or Disease	Intervention/Treatment	Phase
Poliomyelitis	Biological: Oral Polio Vaccine	Phase 4

Detailed Description

This will be a single center, open study in children (aged 1 to 5 years) and vaccine-naïve infants, as follows: 50 OPV-vaccinated children aged 1 to 5 years to receive 1 dose of tOPV (Group 1); 104 vaccine-naïve infants to receive 3 doses of tOPV administered 28 days apart (Group 2)

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase 4 Study to Evaluate the Safety and Immunogenicity of Trivalent Oral Polio Vaccine in Healthy Polio Vaccinated Children 1 to 5 Years of Age and in Healthy Unvaccinated Infants at 6 Weeks of Age in the Dominican Republic
• Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Aug 11, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Oral Polio Vaccine Opvero™ (oral) is a trivalent, live attenuated poliomyelitis virus vaccine containing at least 6.0 log 50% cell culture infective dose (CCID50) of LS c2ab strain of live attenuated polio virus type 1, 5.0 log CCID50 of P712, Ch, 2ab strain of live attenuated polio virus type 2, 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. Excipients: human albumin, HEPES buffer solution, magnesium chloride solution (containing polysorbate 80 and phenol red), hydrochloric acid or sodium hydroxide for pH adjustment. The vaccine is presented as a suspension for oral administration. One dose of vaccine (0.1 ml) is contained in two drops which are delivered from the dropper supplied with the multidose container.

Biological: Oral Polio Vaccine; Opvero™ (oral) is a trivalent, live attenuated poliomyelitis virus vaccine containing at least 6.0 log 50% cell culture infective dose (CCID50) of LS c2ab strain of live attenuated polio virus type 1, 5.0 log CCID50 of P712, Ch, 2ab strain of live attenuated polio virus type 2, 5.8 log CCID50 Leon I2aIb strain of polio virus type 3. Excipients: human albumin, HEPES buffer solution, magnesium chloride solution (containing polysorbate 80 and phenol red), hydrochloric acid or sodium hydroxide for pH adjustment. The vaccine is presented as a suspension for oral administration. One dose of vaccine (0.1 ml) is contained in two drops which are delivered from the dropper supplied with the multidose container.

Outcome Measures

Primary Outcome Measures

1. SAEs and AEs G3 [6 months]

   Number of subjects experiencing SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine 28 days after three doses of SABIN tOPV in vaccine-naïve infants in Dominican Republic.

2. Seroprotection Rate [3 months]

   Seroprotection rate of type-specific polio neutralizing antibodies at Day 84, 28 days after the third dose of SABIN tOPV in infants (Group 2).

Secondary Outcome Measures

1. Neutralizing Antibodies [3 months]

   Median titers and geometric mean antibody titers (GMT) of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2).

2. Seroconversion Rate [3 months]

   Seroconversion rate of type-specific neutralizing antibodies at Day 28 for Group 1, and at Day 84 for Group 2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Weeks to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Age:

Group 1- Children aged 1-5 years, previously vaccinated with ≥ 3 doses of OPV. Group 2- Infants aged 6 weeks (-7 to +14 days) with no previous polio vaccinations.

1. Healthy without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination.

2. Written informed consent obtained from 1 or 2 parents or legal guardians as per Dominican Republic regulations.

Exclusion Criteria:

1. Previous Vaccinations:

Group 1: Previous vaccination against poliovirus outside of the national immunization schedule and any vaccine in the previous 4 weeks.

Group 2: Any vaccination against poliovirus

1. Group 2: Infants with birth weight (BW) < 2,500 gm.

2. Any confirmed or suspected immunosuppressive or known immunodeficient condition including human immunodeficiency virus (HIV) infection.

3. Family history of congenital or hereditary immunodeficiency.

4. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).

5. Known allergy to any component of the study vaccines or to any antibiotics.

6. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections.

7. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

8. Acute severe febrile illness at day of vaccination deemed by the Investigator to be a contraindication for vaccination (the child can be included at a later time if within age window and all in/exclusion criteria are met).

9. Member of the subject's household (living in the same house or apartment unit) has received OPV in the last 3 months, or is scheduled to receive OPV during the study period.

10. Subject who, in the opinion of the Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Fidec Corporation
• Bill and Melinda Gates Foundation

Investigators

• Principal Investigator: Luis Rivera, MD, Hospital Maternidad Nuestra Señora de la Altagracia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fidec Corporation
• ClinicalTrials.gov Identifier: NCT02580201
• Other Study ID Numbers: T2-ABMG
• First Posted: Oct 20, 2015
• Last Update Posted: Sep 1, 2020
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Poliomyelitis

Study Results

Participant Flow

Arm/Group Title	Group1	Group 2
Arm/Group Description	tOPV-vaccinated healthy children to receive 1 dose of SABIN tOPV	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
Period Title: Overall Study
STARTED	50	104
COMPLETED	50	104
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group 1	Group 2	Total
Arm/Group Description	tOPV-vaccinated healthy children aged 1 to 5 years to receive 1 dose of SABIN	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart	Total of all reporting groups
Overall Participants	50	104	154
Age (Count of Participants)
<=18 years	50 100%	104 100%	154 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex/Gender, Customized (Count of Participants)
Female	23 46%	56 53.8%	79 51.3%
Male	27 54%	48 46.2%	75 48.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	50 100%	104 100%	154 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Dominican Republic	50 100%	104 100%	154 100%

Outcome Measures

1. Primary Outcome

Title	SAEs and AEs G3
Description	Number of subjects experiencing SAEs and severe AEs grade 3 considered consistent with a causal association to study vaccine 28 days after three doses of SABIN tOPV in vaccine-naïve infants in Dominican Republic.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Total vaccinated population (TVP)

Arm/Group Title	Group1	Group 2
Arm/Group Description	tOPV-vaccinated healthy children to receive 1 dose of SABIN tOPV	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
Measure Participants	50	104
Count of Participants [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Seroprotection Rate
Description	Seroprotection rate of type-specific polio neutralizing antibodies at Day 84, 28 days after the third dose of SABIN tOPV in infants (Group 2).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Per Protocol Population (PP)

Arm/Group Title	Group 2
Arm/Group Description	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
Measure Participants	104
Serotype 1	93.3
Serotype 2	100
Serotype 3	96.2

3. Secondary Outcome

Title	Neutralizing Antibodies
Description	Median titers and geometric mean antibody titers (GMT) of type-specific neutralizing antibodies at Days 0 and 28 in children aged 1-5 years (Group 1), and at Days 0 and 84 in infants (Group 2).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Per Protocol Population (PP)

Arm/Group Title	Group1	Group 2
Arm/Group Description	tOPV-vaccinated healthy children to receive 1 dose of SABIN tOPV	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
Measure Participants	49	104
Serotype 1	10.50	10.50
Serotype 2	9.83	10.17
Serotype 3	8.50	8.83

4. Secondary Outcome

Title	Seroconversion Rate
Description	Seroconversion rate of type-specific neutralizing antibodies at Day 28 for Group 1, and at Day 84 for Group 2.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Per protocol population (PP)

Arm/Group Title	Group1	Group 2
Arm/Group Description	tOPV-vaccinated healthy children to receive 1 dose of SABIN tOPV	Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
Measure Participants	49	104
Serotype 1	32.7	88.5
Serotype 2	36.7	98.1
Serotype 3	46.9	96.2

Adverse Events

Time Frame	3.5 months
Adverse Event Reporting Description	Safety analyses were performed for solicited and unsolicited AEs by severity using the CTCAE version 4.03 published by NIH in 2010, as well as for SAEs and IMEs.
Arm/Group Title	Group1		Group 2
Arm/Group Description	tOPV-vaccinated healthy children to receive 1 dose of SABIN tOPV		Vaccine-naïve infants to receive 3 doses of SABIN tOPV administered 28 days apart.
All Cause Mortality
	Group1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/104 (0%)
Serious Adverse Events
	Group1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/104 (0%)
Other (Not Including Serious) Adverse Events
	Group1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/50 (16%)		52/104 (50%)
Gastrointestinal disorders
Appetite lost	1/50 (2%)	2	3/104 (2.9%)	8
Vomiting	1/50 (2%)	1	8/104 (7.7%)	25
Diarrhea	0/50 (0%)	0	2/104 (1.9%)	2
General disorders
Abnormal crying	1/50 (2%)	1	5/104 (4.8%)	20
Drowsiness	0/50 (0%)	0	3/104 (2.9%)	5
Fever	3/50 (6%)	5	8/104 (7.7%)	19
Irritability	0/50 (0%)	0	6/104 (5.8%)	12
Infections and infestations
Ear infection	1/50 (2%)	1	1/104 (1%)	1
Nasopharyngitis	0/50 (0%)	0	9/104 (8.7%)	18
Conjunctivitis	0/50 (0%)	0	1/104 (1%)	1
Amoebic dysentery	0/50 (0%)	0	1/104 (1%)	1
Bronchiolitis	0/50 (0%)	0	1/104 (1%)	1
Dengue Fever	0/50 (0%)	0	1/104 (1%)	1
Urinary tract infection	0/50 (0%)	0	1/104 (1%)	1
Injury, poisoning and procedural complications
Head injury	0/50 (0%)	0	1/104 (1%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	1/50 (2%)	1	1/104 (1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.