Safety and Immunogenicity (Non-inferiority) of a Purified Chick Embryo Cell Vaccine Vaccine Administered in Two Different Schedules (Conventional Versus Abbreviated Schedule)

A Phase III, Single Center, Randomized, Open-label Study, Comparing PCECV Administered in the Abbreviated Zagreb Regimen (2-1-1) to the Conventional Essen Regimen (1-1-1-1-1) in Healthy Volunteers in China

This study investigates the safety and immunogenicity (non-inferiority) of a Purified Chick Embryo Cell Vaccine (PCECV) administered in two different schedules (conventional versus abbreviated schedule) in healthy adults 18 to 50 years of age in China

Study Overview

• Status: Completed
• Conditions: Rabies
• Intervention / Treatment: Biological: Abbreviated Zagreb 2-1-1 schedule; Biological: Standard Essen 1-1-1-1-1 schedule

• Study Type: Interventional
• Enrollment (Actual): 825
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hebei
    • Jizhou City, Hebei, China, 053200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects 18-50 years of age who:
• are in good health at the time of entry into the study as determined by medical history, physical examination and clinical judgment of the investigator;
• volunteer for the simulated post-exposure vaccination courses and blood draws;
• have given a written informed consent; informed consent must be obtained for all the subjects before enrolment in the study;
• are available for all the visits scheduled in the study.

Exclusion Criteria:

• Subjects with the below criteria were excluded:
• pregnancy or unwillingness to practice acceptable contraception during participation in the study;
• a history of rabies immunization;
• a significant acute or chronic infectious disease that may impact the subject's safety and /or immunogenicity in the Investigators opinion at the time of enrolment;
• fever ≥ 38.0°C (axillary) or/and significant acute or chronic infection requiring systemic antibiotic or antiviral therapy within the past 7 days before enrolment;
• treatment with corticosteroids, immunosuppressive or antimalaria drugs during the two month period before enrolment;
• administration of any vaccine within the past 14 days before enrolment;
• known/suspected immunodeficiency, or autoimmune disease, or any immunologic disorder;
• history of allergy to egg protein;
• known hypersensitivity to neomycin, tetracycline, amphotericin-B, or any other vaccine component;
• treatment with parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months;
• mental condition rendering the subject unable to understand the nature, scope and consequences of the study;
• participation in any other investigational trial within the past 3 months before enrolment;
• planned surgery during the study period;
• intention to leave the area of the study site before the end of study period;
• any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objective.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zagreb (2-1-1); Rabies PCEC vaccine was applied according Zagreb schedule with 2 vaccinations on day 0, 1 vaccination on day 7 and day 21, respectively	Biological: Abbreviated Zagreb 2-1-1 schedule; Subjects received the abbreviated Zagreb 2-1-1 schedule in a safety-lead-in phase.; Other Names: PCEC Rabies vaccine for human use
Active Comparator: Essen (1-1-1-1-1); Rabies PCEC vaccine was applied according Essen schedule, i.e. 1 vaccination on day 0, day 3, day 7, day 14 and day 28, respectively.	Biological: Standard Essen 1-1-1-1-1 schedule; Subjects received the standard Essen regimen.; Other Names: PCEC Rabies vaccine for human use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rabies Virus Neutralizing Antibody Concentrations on Day 14.	Rabies virus neutralizing antibody concentrations of the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2.	14 days
Number of Participants Who Reported a Local or Systemic Reaction After Any Vaccination	Specified local and systemic reactions were solicited for 7 days after each vaccination. Number of participants were calculated who reported a local or systemic reaction after any of the vaccinations.	7 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rabies Virus Neutralizing Antibody Concentrations on Day 7 and Day 42.	Rabies virus neutralizing antibody concentrations the abbreviated Zagreb regimen compared with the conventional Essen regimen. Results are presented on log2 scale. For results on original geometric (multiplicative) scale please raise numbers to the basis of 2.	7 days and 42 days
Percentages of Participants With Seroconversion (Rabies Virus Neutralizing Antibody Concentrations Equal and Above 0.5 IU/ml) on Days 7, 14 and 42.	Percentages of participants with seroconversion (defined as rabies virus neutralizing antibody concentrations equal and above 0.5 IU/ml) on days 7, 14 and 42.	7 days, 14 days and 42 days

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Ma J, Wang H, Li J, Chang L, Xie Y, Liu Z, Zhao Y, Malerczyk C. A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults. Hum Vaccin Immunother. 2014;10(10):2805-12. doi: 10.4161/21645515.2014.972773. Erratum In: Hum Vaccin Immunother. 2015;11(5):1295. Claudius, Malerczyk [corrected to Malerczyk, Claudius].

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: January 19, 2009
• First Submitted That Met QC Criteria: January 20, 2009
• First Posted (Estimate): January 21, 2009

Study Record Updates

• Last Update Posted (Estimate): December 13, 2011
• Last Update Submitted That Met QC Criteria: December 7, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: vaccine; prevention; Rabies disease; rabies
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: M49P8