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

Phase 2

Completed

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

Brief 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).

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
CL184+PVRV	Rabies virus-specific monoclonal antibodies	CL184 with rabies vaccine (PVRV)
CL184+PVRV	Purified verocell rabies vaccine (PVRV)	CL184 with rabies vaccine (PVRV)
HRIG+PVRV	human polyclonal rabies immune globulin (HRIG)	HRIG with rabies vaccine
CL184+HDCV	Rabies virus-specific monoclonal antibodies	CL184 with rabies vaccine (HDCV)
CL184+HDCV	Human diploid cell vaccine (HDCV)	CL184 with rabies vaccine (HDCV)
Placebo+HDCV	Placebo	Placebo with rabies vaccine (HDCV)
Placebo+HDCV	Human diploid cell vaccine (HDCV)	Placebo with rabies vaccine (HDCV)
HRIG+PVRV	Purified verocell rabies vaccine (PVRV)	HRIG with rabies vaccine
Placebo+PVRV	Placebo	Placebo with rabies vaccine (PVRV)
Placebo+PVRV	Purified verocell rabies vaccine (PVRV)	Placebo with rabies vaccine (PVRV)

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events as a measure of safety	90 days	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