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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Rabies

Intervention / Treatment
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* 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)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CL184+PVRV<br>CL184 with rabies vaccine (PVRV) | Biological: Rabies virus-specific monoclonal antibodies<br>* CL184 20 IU/kg intramuscularly on Day 0.<br>* Other names: CL184;Biological: Purified verocell rabies vaccine (PVRV)<br>* Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.<br>* Other names: Verorab™;|
| Active Comparator: HRIG+PVRV<br>HRIG with rabies vaccine | Biological: human polyclonal rabies immune globulin (HRIG)<br>* HRIG 20 IU/kg intramuscularly on Day 0.<br>* Other names: Imogam® Rabies-HT;Biological: Purified verocell rabies vaccine (PVRV)<br>* Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.<br>* Other names: Verorab™;|
| Placebo Comparator: Placebo+PVRV<br>Placebo with rabies vaccine (PVRV) | Biological: Placebo<br>* Placebo intramuscularly on Day 0.<br>Biological: Purified verocell rabies vaccine (PVRV)<br>* Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.<br>* Other names: Verorab™;|
| Experimental: CL184+HDCV<br>CL184 with rabies vaccine (HDCV) | Biological: Rabies virus-specific monoclonal antibodies<br>* CL184 20 IU/kg intramuscularly on Day 0.<br>* Other names: CL184;Biological: Human diploid cell vaccine (HDCV)<br>* Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.<br>* Other names: Imovax®;|
| Placebo Comparator: Placebo+HDCV<br>Placebo with rabies vaccine (HDCV) | Biological: Placebo<br>* Placebo intramuscularly on Day 0.<br>Biological: Human diploid cell vaccine (HDCV)<br>* Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.<br>* Other names: Imovax®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rabies virus neutralizing activity |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rabies, Monoclonal antibody, Post-exposure prophylaxis