Studies of the Safety and Immunogenicity of a Sabin Inactivated Poliovirus Vaccine

A Open-label Phase I Study to Evaluate Safety of a Sabin Inactivated Poliovirus Vaccine (sIPV) in Adults, Children, and Infants, and a Blinded, Randomized and Controlled Phase II to Evaluate Safety and Immunogenicity of it in Infants

The purpose of this study is to evaluate the safety of sIPVs of different dosages in adults, children and infants in a phase I open-label study, and then assess its immunogenicity and safety in healthy infants between 60 and 90 days old in a phase II blind, randomized, and controlled study.

Study Overview

• Status: Completed
• Conditions: Poliomyelitis
• Intervention / Treatment: Biological: Single-dose regimen of high dosage investigational sIPV; Biological: Single-dose regimen of medium dosage investigational sIPV; Biological: Three-dose regimen of high dosage investigational sIPV; Biological: Three-dose regimen of medium dosage investigational sIPV; Biological: Three-dose regimen of low dosage investigational sIPV; Biological: Three-dose regimen of commercialized sIPV; Biological: Three-dose regimen of commercialized IPV

Detailed Description

This study is a combination of phases I and II. Phase I study is open-label, and only collect safety information of the investigational sIPVs in adults, children and infants. Phase II study is double-blind, randomized, controlled study of the immunogenicity and safety of the investigational vaccines and two other commercialized inactivated poliovirus vaccines in healthy infants.

• Study Type: Interventional
• Enrollment (Actual): 708
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221300
      • Pizhou City Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 49 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteer between 60-90 days old, 6-12 years old, or 18-49 years old;
• Healthy volunteers who fulfill all the required conditions for receiving the investigational vaccine as established by medical history and clinical examination and determined by investigators;
• Proven legal identity;
• Participants (≥ 18 years old), or guardians of the participants (< 18 years old) should be capable of understanding the written consent form, and such form should be signed prior to enrolment;
• Complying with the requirement of the study protocol;
• Axillary temperature ≤ 37.0 °C;

Exclusion Criteria:

• Breast feeding, pregnant, or expected to conceive in the next 60 days;
• History of allergy to any vaccine, or any ingredient of the vaccine, or serious adverse reaction(s) to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc;
• Congenital malformation, developmental disorders, genetic defects, or severe malnutrition;
• Autoimmune disease or immunodeficiency/immunosuppressive;
• serious chronic diseases, serious cardiovascular disease, hypertension or diabetes that cannot be stabilized by medication, liver or kidney disease, malignancy, etc;
• severe nervous system disease (epilepsy, seizures or convulsions) or mental illness;
• History of thyroidectomy, asplenia, functional asplenia, or any condition resulting in the absence or removal the spleen;
• Bleeding disorder diagnosed by a doctor (e.g., coagulation factor deficiency, coagulation disorder, or platelet disorder) , or significant bruising or coagulopathy;
• Long term history of alcoholism or drug abuse;

• Receipt of any of the following products:

  1. Any subunit or inactivated vaccine within the past 7 day;
  2. Any live attenuated vaccine within the past 14 days;
  3. Any other investigational medicine(s) within the past 30 days;
  4. Any blood product within the past 3 months;
  5. Any immunosuppressant, cytotoxic medications, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) within the past 6 month prior to study entry;
• Acute illness or acute exacerbation of chronic disease within the past 7 days;
• Axillary temperature > 37.0 °C;
• Infant participants with prior vaccination of poliovirus;
• Any other factor that, in the judgment of the investigator, suggesting the volunteer is unsuitable for this study;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Adult Group - High dosage; Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0;; Intervention: Single-dose regimen of high dosage investigational sIPV	Biological: Single-dose regimen of high dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Adult Group - Medium dosage; Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0;; Intervention: Single-dose regimen of medium dosage investigational sIPV	Biological: Single-dose regimen of medium dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Child Group - High dosage; Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0;; Intervention: Single-dose regimen of high dosage investigational sIPV	Biological: Single-dose regimen of high dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Child Group - Medium dosage; Single intramuscular injection of the investigational vaccine(0.5 ml) on Day 0;; Intervention: Single-dose regimen of medium dosage investigational sIPV	Biological: Single-dose regimen of medium dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Infant Group - High dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of high dosage investigational sIPV	Biological: Three-dose regimen of high dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Infant Group - Medium dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of medium dosage investigational sIPV	Biological: Three-dose regimen of medium dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: Phase I Infant Group - Low dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of low dosage investigational sIPV	Biological: Three-dose regimen of low dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: PhaseⅡExperimental Group - High dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of high dosage investigational sIPV	Biological: Three-dose regimen of high dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: PhaseⅡExperimental Group - Medium dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of medium dosage investigational sIPV	Biological: Three-dose regimen of medium dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Experimental: PhaseⅡExperimental Group - Low dosage; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of low dosage investigational sIPV	Biological: Three-dose regimen of low dosage investigational sIPV; The investigational vaccines were manufactured by Sinovac Biotech Co., Ltd..
Active Comparator: PhaseⅡControl Group -commercialized sIPV; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention:Three-dose regimen of commercialized sIPV	Biological: Three-dose regimen of commercialized sIPV; The control vaccine was manufactured by Chinese Academy of Medical Sciences.
Active Comparator: PhaseⅡ Control Group -commercialized IPV; Three intramuscular injections of the investigational vaccine(0.5 ml) on Day 0, Day 30 and Day 60 respectively;; Intervention: Three-dose regimen of commercialized IPV	Biological: Three-dose regimen of commercialized IPV; The control vaccine was manufactured by Sanofi Pasteur S.A (IMOVAX POLIO).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The seroconversion rates (SCRs) of each group of the phase II trial after three-dose regimen	Subjects whose pre-immune antibody level < 1:8 and post-immune antibody level ≥ 1:8, or those whose pre-immune antibody level ≥ 1:8 and the increase of post-immune antibody level ≥ 4 folds are considered seroconverted.	90 days
The post-immune geometric mean titer (GMT) of each group of the phase II trial after three-dose regimen	GMT of each group of the phase II trial 30 days after three-dose regimen which lasts 60 days.	90 days
The geometric mean fold increase (GMI) of each group after three-dose regimen	The GMI is the increase of post-immune GMT from pre-immune GMT.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidences of solicited adverse events (AEs) of each group in both phase I and II trials	Solicited AEs occurred within 7 days after each injection will be collected.	7 days
The incidences of unsolicited adverse events (AEs) of each group in both phase I and II trials	Unsolicited AEs occurred within 30 days after each injection will be collected.	30 days
The incidences of serious adverse events (SAEs) of each group in both phase I and II trials	SAEs occurred within 30 days after each injection will be collected.	30 days

Collaborators and Investigators

• Sponsor: Sinovac Biotech Co., Ltd

Publications and helpful links

General Publications

• Chu K, Ying Z, Wang L, Hu Y, Xia J, Chen L, Wang J, Li C, Zhang Q, Gao Q, Hu Y. Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: A phase II, randomized, dose-finding trial. Vaccine. 2018 Oct 29;36(45):6782-6789. doi: 10.1016/j.vaccine.2018.09.023. Epub 2018 Sep 21.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: December 5, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 7, 2016

Study Record Updates

• Last Update Posted (Actual): July 26, 2017
• Last Update Submitted That Met QC Criteria: July 25, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: safety; immunogenicity; poliomyelitis; infant; Sabin strain; Inactivated poliovirus 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
• Other Study ID Numbers: PRO-sIPV-1001

Plan for Individual participant data (IPD)

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