Rabies Virus Neutralizing Activity and Safety of CL184, a Monoclonal Antibody Cocktail, in Simulated Rabies Post-Exposure Prophylaxis in Healthy Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Crucell Holland BV
ClinicalTrials.gov Identifier:
NCT01228383
First received: October 13, 2010
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

Study design:

Single-blind (subject and observer-blinded), active-controlled, randomized [6:2:1:2:1; CL184 + purified vero cell rabies vaccine (PVRV) vs. human rabies immune globulin (HRIG) + PVRV vs. placebo + PVRV vs. CL184 + human diploid cell vaccine (HDCV) vs. placebo + HDCV], mono-center study

Study objectives:

Primary: To evaluate the safety of CL184 in combination with PVRV in healthy adult subjects.

Secondary: To evaluate the safety of HRIG or placebo in combination with PVRV and to evaluate the safety of CL184 or placebo in combination with HDCV in healthy adult subjects. To evaluate the rabies virus neutralizing activity (RVNA) after administration of CL184 or placebo in combination with PVRV, of HRIG in combination with PVRV, and of CL184 or placebo in combination with HDCV in healthy adult subjects. To evaluate the pharmacokinetics of the monoclonal antibodies (mAbs).


Condition Intervention Phase
Rabies
Biological: Rabies virus-specific monoclonal antibodies
Biological: human polyclonal rabies immune globulin (HRIG)
Biological: Placebo
Biological: Human diploid cell vaccine (HDCV)
Biological: Purified verocell rabies vaccine (PVRV)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Randomized, Single-blind, Active-controlled, Mono-center Phase II Study to Compare the Safety and Neutralizing Activity of Simulated Rabies Post-exposure Prophylaxis With CL184 in Combination With Purified Vero Cell Rabies Vaccine vs. Human Rabies Immune Globulin or Placebo in Combination With Purified Vero Cell Rabies Vaccine vs. CL184 or Placebo in Combination With Human Diploid Cell Rabies Vaccine in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by Crucell Holland BV:

Primary Outcome Measures:
  • Number of participants with adverse events as a measure of safety [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Assessed by recording unsolicited adverse events, solicited local and systemic adverse events, and pain at the injection site (assessed on a Visual Analog Scale from Day 0 to Day 3); routine safety laboratory assessed on Days -1, 1, 3, 7, 42, and 90; ECG and vital signs assessed on Days -1, 7, and 90.


Secondary Outcome Measures:
  • Rabies virus neutralizing activity [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Enrollment: 240
Study Start Date: December 2011
Study Completion Date: December 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CL184+PVRV
CL184 with rabies vaccine (PVRV)
Biological: Rabies virus-specific monoclonal antibodies
CL184 20 IU/kg intramuscularly on Day 0.
Other Name: CL184
Biological: Purified verocell rabies vaccine (PVRV)
Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.
Other Name: Verorab™
Active Comparator: HRIG+PVRV
HRIG with rabies vaccine
Biological: human polyclonal rabies immune globulin (HRIG)
HRIG 20 IU/kg intramuscularly on Day 0.
Other Name: Imogam® Rabies-HT
Biological: Purified verocell rabies vaccine (PVRV)
Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.
Other Name: Verorab™
Placebo Comparator: Placebo+PVRV
Placebo with rabies vaccine (PVRV)
Biological: Placebo
Placebo intramuscularly on Day 0.
Biological: Purified verocell rabies vaccine (PVRV)
Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.
Other Name: Verorab™
Experimental: CL184+HDCV
CL184 with rabies vaccine (HDCV)
Biological: Rabies virus-specific monoclonal antibodies
CL184 20 IU/kg intramuscularly on Day 0.
Other Name: CL184
Biological: Human diploid cell vaccine (HDCV)
Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.
Other Name: Imovax®
Placebo Comparator: Placebo+HDCV
Placebo with rabies vaccine (HDCV)
Biological: Placebo
Placebo intramuscularly on Day 0.
Biological: Human diploid cell vaccine (HDCV)
Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.
Other Name: Imovax®

Detailed Description:

This study was designed to explore and obtain further safety and RVNA data on CL184 in comparison to HRIG and placebo as part of a classical post-exposure prophylaxis (PEP) regimen. This regimen will be applied as simulated PEP regimen to healthy subjects (i.e. in a pre-exposure setting) in this study. A comparison with placebo combined with each rabies vaccine was included to differentiate between the contribution of immune globulin and vaccine and to investigate potential interactions between immune globulin and vaccine. RVNA provided by CL184 or HRIG, as well as vaccination response will be checked regularly during the study and booster doses can be applied after the study, if necessary. In addition pharmacokinetic data will be collected.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female subject aged ≥18 to ≤55 years
  • Subjects free of obvious health-problems or with stable conditions or medications
  • Body mass index between ≥18 to ≤30 kg/m2
  • Abstinence from sexual intercourse or use of adequate contraception from the date of screening up to Day 90
  • Male subjects must agree that they will not donate sperm from the first check-in until Day 90
  • Subject signed written informed consent

Exclusion Criteria:

  • Prior history of active or passive rabies immunization
  • Clinically significant acute illness or infection including fever (≥38 °C) within 2 weeks before first dosing
  • History and/or family history of clinically significant immunodeficiency or auto-immune disease
  • Planned immunization with live vaccines during the coming 3 months after first dosing
  • Chronic (longer than 14 days) administration of immunosuppressants or other immune-modifying drugs within 6 months before the first dose of investigational medicinal product
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01228383

Locations
India
Lotus House, Vasanth Nagar
Bangalore, Karnataka, India, 560 052
Sponsors and Collaborators
Crucell Holland BV
Investigators
Principal Investigator: G Nagashayana, MD Lotus Labs Pvt. Ltd, Bangalore, India
  More Information

No publications provided

Responsible Party: Crucell Holland BV
ClinicalTrials.gov Identifier: NCT01228383     History of Changes
Other Study ID Numbers: RAB-M-A008, U1111-1120-1647
Study First Received: October 13, 2010
Last Updated: April 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Crucell Holland BV:
Monoclonal antibody
Rabies
Post-exposure prophylaxis

Additional relevant MeSH terms:
Rabies
Rhabdoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Virus Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014