Randomized Controlled Trial for Immunogenicity and Safety Evaluation of Bivalent Types 1 and 3 Oral Poliovirus Vaccine (TTbOPV)

Immunogenicity and Safety Evaluation of Bivalent Types 1 and 3 Oral Poliovirus Vaccine by Comparing Different Poliomyelitis Vaccination Schedules in Chinese Infant: a Randomized Controlled Non-Inferiority Clinical Trial

Type 2 component of oral poliovirus vaccine is slated for global withdrawal through a switch from trivalent oral poliovirus vaccine (tOPV) to bivalent oral poliovirus vaccine (bOPV) for preventing paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess immunogenicity and safety profile of six vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV.

Study Overview

• Status: Completed
• Conditions: Poliomyelitis
• Intervention / Treatment: Biological: poliovirus vaccine

Detailed Description

A randomized controlled trial was conducted in China in 2015. After informed consent was obtained from a parent or legally acceptable representative, healthy newborn babies were randomly allocated to one of six groups: cIPV-bOPV-bOPV, cIPV-tOPV-tOPV, cIPV-cIPV-bOPV, cIPV-cIPV-tOPV, cIPV-cIPV-cIPV, and tOPV-tOPV-tOPV. The key eligibility criteria were: full-term birth (37-42 weeks of gestation), birthweight ≥2·5 kg, no obvious medical disorders and no polio vaccination. Infants received following three doses sequentially with 4- 6 weeks interval after collecting blood sample: cIPV-bOPV-bOPV, cIPV-tOPV-tOPV, cIPV-cIPV-bOPV, cIPV-cIPV-tOPV, cIPV-cIPV-cIPV, and tOPV-tOPV-tOPV; and will be proactively followed up for observing adverse events after the first dose and 30 days after all doses. Antibodies of type 1, 2, and 3 poliovirus were tested 30 days after the third dose. The primary study objective was to investigate immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titre against poliovirus types 1, 2, and 3 in the per-protocol population.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eligible participants were healthy full-term (37-42 weeks) infants aged 60-90 days who weighed more than 2·5 kg at birth with no obvious medical disorders, no polio vaccination, no immunoglobulin vaccinated, no other attenuated vaccine immured in the past 14 days and no other inactivated vaccine immured.

Exclusion Criteria:

• Participants were excluded if meet one or more of following criteria: were or were at risk of immunodeficiency, severe allergic reaction, acute fever and infectious diseases, severe chronic diseases, family history of allergies, convulsions, seizures, encephalopathy and psychiatric diseases, oral steroids at least 14 consecutive days in the past month, axillary temperature equal or greater than 38·0°C in the past three days, diarrhea (defection frequency equal or greater than three times per day) in the past seven days, and participated in other drug clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cIPV-bOPV-bOPV poliovirus vaccine; Participants would be vaccine with trivalent conventional inactivated poliovirus vaccine, and two bivalent types 1 and 3 oral poliovirus vaccine sequentially.	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine
Experimental: cIPV-tOPV-tOPV poliovirus vaccine; Participants would be vaccine with trivalent conventional inactivated poliovirus vaccine, and two trivalent types 1, 2 and 3 oral poliovirus vaccine sequentially.	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine
Experimental: cIPV-cIPV-bOPV poliovirus vaccine; Participants would be vaccine with two shots of trivalent conventional inactivated poliovirus vaccine, and one bivalent types 1 and 3 oral poliovirus vaccine sequentially.	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine
Experimental: cIPV-cIPV-tOPV poliovirus vaccine; Participants would be vaccine with two shots of trivalent conventional inactivated poliovirus vaccine, and one trivalent types 1, 2 and 3 oral poliovirus vaccine sequentially.	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine
Experimental: cIPV-cIPV-cIPV poliovirus vaccine; Participants would be vaccine with three shots of trivalent conventional inactivated poliovirus vaccine.	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine
Experimental: tOPV-tOPV-tOPV poliovirus vaccine; Participants would be vaccine with three times of trivalent types 1, 2 and 3 oral poliovirus vaccine .	Biological: poliovirus vaccine; Different vaccination schedules with bOPV, tOPV and cIPV would be provided for 6 arms respectively.; Other Names: bivalent types 1 and 3 oral poliovirus vaccine; trivalent conventional inactivated poliovirus vaccine; trivalent types 1, 2 and 3 oral poliovirus vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infants with seroconversion	Primary immunogenicity outcome was the proportion of infants with seroconversion, which was defined as the 30 days post-vaccination titer equal or greater than eight for susceptible infants and the post-vaccination titer is four times higher than pre-vaccination titer for unsusceptible infants. Here, susceptible infants are the ones whose pre-vaccination titer less than eight. Otherwise, the subjects are categories as unsusceptible ones.	30 days after vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall seroprotection rate	Overall seroprotection rate was defined as the proportion of subjects with reciprocal titre of at least eight.	30 days after vaccination
Geometric mean of antibody titres (GMT)		30 days after vaccination
Increase of geometric mean of antibody titres (GMI)		30 days after vaccination
Proportion of infants with serious adverse events		Six months after vaccination
Solicited adverse events	Solicited adverse events involving both systemic reactions (including fever, irritability/fussiness, somnolence, vomit, diarrhea, and allergic reaction) and local reactions (including tenderness, redness, swelling, and callous around the injection sites).	30 days after vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of infants with seroconversion in susceptible population	Proportion of infants with seroconversion, which was defined as the 30 days post-vaccination titer equal or greater than eight for susceptible infants. Here, susceptible infants are the ones whose pre-vaccination titer less than eight.	30 days after vaccination
Proportion of infants with seroconversion in unsusceptible population	Proportion of infants with seroconversion, which was defined as the 30 days post-vaccination titer is four times higher than pre-vaccination titer for unsusceptible infants.	30 days after vaccination

Collaborators and Investigators

• Sponsor: Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control
• Collaborators: Air Force Military Medical University, China; Beijing Tiantan Biological Products Co., Ltd.
• Investigators: Principal Investigator: Zhaojun Mo, Center of Diseases Control and Prevention (CDC) of Hezhou County and Zhongshan County in Guangxi Zhuang Autonomous Region in China

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: May 25, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 30, 2016

Study Record Updates

• Last Update Posted (Estimate): May 30, 2016
• Last Update Submitted That Met QC Criteria: May 25, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: poliomyelitis; polio; immunization; oral polio vaccine; vaccine schedule; inactivated polio vaccine
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Neuromuscular Diseases; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Myelitis; Poliomyelitis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: Tiantan-201417903

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No