Immunogenicity and Safety of Rabies Vaccine, Administered With Two Different Simulated Post Exposure Schedules

A Phase IV, Multi-center, Randomized, Open-label Study of PCECV (Rabipur®) Comparing the Immunogenicity and Safety of Two Different Simulated Post Exposure Schedules (Zagreb 2-1-1 Versus Essen Regimen 1-1-1-1-1) in Healthy Indian Subjects

This study was planned to establish the non-inferiority of Rabipur administered as simulated post exposure Zagreb schedule as compared to Essen schedule, in healthy Indian adult subjects.

Study Overview

• Status: Completed
• Conditions: Rabies
• Intervention / Treatment: Biological: Purified Chick Embryo Cell Inactivated Rabies Vaccine

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • KA
    • Bangalore, KA, India, 560070
      • Kempegowda Institute of Medical Sciences Hospital (KIMS)
    • Mandya, KA, India, 571401
      • Mandya Institute of Medical Sciences
  • MS
    • Pune, MS, India, 411018
      • Padmashree Dr. D.Y Patil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females of age ≥ 18 years.
2. Individuals who had given written consent.
3. Individuals in good health and available for all the visits scheduled in the study.

Exclusion Criteria:

1. Pregnancy or unwillingness to practice acceptable contraception.
2. A history of Rabies vaccination.
3. History of allergy to egg protein.
4. Known hypersensitivity to neomycin, tetracycline, amphotericin-B or any other vaccine component.
5. A significant acute or chronic infectious disease or use of antibiotics that may impact the subject's safety and /or immunogenicity in the Investigators opinion at the time of enrolment.
6. Body temperature ≥38.0°C (≥ 100.4°F) within 3 days of study vaccination.
7. Treatment with an anti-malarial drug, up to two months prior to the study.
8. Individuals who received any other vaccines within 28 days prior to enrollment.
9. Subjects who have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks.
10. Any planned surgery during the study period.
11. Subjects who have cancer disorders excluding nonmelanotic skin cancer.

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
Active Comparator: Group A-Zagreb; Purified Chick Embryo Cell Inactivated Rabies Vaccine, administered intramuscularly (IM) according to the 2-1-1 (Zagreb) schedule (i.e., 2 doses of vaccine administered on day 0 and 1 dose of vaccine each administered on day 7 and day 21)	Biological: Purified Chick Embryo Cell Inactivated Rabies Vaccine; Two group (Zagreb and Essen) will receive Rabipur vaccine IM according to either Zagreb or Essen schedules.
Active Comparator: Group B-Essen; Purified Chick Embryo Cell Inactivated Rabies Vaccine, administered IM according to the 1-1-1-1-1 (Essen) schedule (i.e., 1 dose of vaccine administered on day 0, 3, 7, 14, and 28)	Biological: Purified Chick Embryo Cell Inactivated Rabies Vaccine; Two group (Zagreb and Essen) will receive Rabipur vaccine IM according to either Zagreb or Essen schedules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Each of the Zagreb and Essen Groups on Study Day 14	Immunogenicity was measured as the geometric mean concentrations (GMCs) of rabies virus neutralizing antibody (RVNA) titer , evaluated using the rapid fluorescent focus inhibition test, before vaccination and on study day 14 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule	On Day 0 and Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Zagreb and Essen Groups at Days 7, 14 and 42	Immunogenicity was measured as the percentage of subjects who achieved anti-RVNA titer ≥0.5 IU/mL, at days 0, 7, 14 and 42 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedule.	Study day 7, 14 and 42
Ratio of GMCs in Study Groups (Zagreb/Essen Schedules) on Days 7 and 42 as Measured by RVNA Geometric Mean Concentrations	Immunogenicity was measured as the ratio of GMCs of RVNA titer , evaluated using the rapid fluorescent focus inhibition test, on Days 7 and 42 as per Zagreb (2-1-1) and Essen (1-1-1-1-1) postexposure schedules	Day 0, Day 7, Day 14 and Day 42
Percentages of Subjects Reporting Adverse Events (AEs)	Adverse events (AEs) were collected for 7 days following administration of each study vaccination or until time of next vaccination (whichever occurred sooner). All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects during the study were collected throughout the study period and all AEs were unsolicited.	All reported SAEs and medically attended AEs or AEs that resulted in the premature withdrawal of subjects were collected up to 42 days after first vaccination. Adverse events were collected throughout the study period

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Mahendra BJ, Narayana DA, Agarkhedkar S, Ravish HS, Harish BR, Agarkhedkar S, Madhusudana SN, Belludi A, Ahmed K, Jonnalagedda R, Vakil H, Bhusal C, Arora AK. Comparative study on the immunogenicity and safety of a purified chick embryo cell rabies vaccine (PCECV) administered according to two different simulated post exposure intramuscular regimens (Zagreb versus Essen). Hum Vaccin Immunother. 2015;11(2):428-34. doi: 10.4161/21645515.2014.995059.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 30, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 3, 2011

Study Record Updates

• Last Update Posted (Estimate): May 5, 2014
• Last Update Submitted That Met QC Criteria: April 3, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Rabies; post-exposure prophylaxis; rabies vaccines
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Rhabdoviridae Infections; Rabies
• Other Study ID Numbers: V49_25