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

Rabies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01228383
• Other study ID #: RAB-M-A008
• Secondary ID: U1111-1120-1647
• Status: Completed
• Phase: Phase 2
• First received: October 13, 2010
• Last updated: April 3, 2013
• Start date: December 2011
• Est. completion date: December 2012

Study information

• Verified date: April 2013
• Source: Crucell Holland BV
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Rabies

Intervention

Biological:
• Rabies virus-specific monoclonal antibodies
CL184 20 IU/kg intramuscularly on Day 0.
• human polyclonal rabies immune globulin (HRIG)
HRIG 20 IU/kg intramuscularly on Day 0.
• Placebo
Placebo intramuscularly on Day 0.
• Human diploid cell vaccine (HDCV)
Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.
• Purified verocell rabies vaccine (PVRV)
Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.

Locations

Country	Name	City	State
India	Lotus House, Vasanth Nagar	Bangalore	Karnataka

Sponsors (1)

Lead Sponsor	Collaborator
Crucell Holland BV

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events as a measure of safety	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.	90 days	Yes
Secondary	Rabies virus neutralizing activity		90 days	No