Rabies
Conditions
Keywords
Monoclonal antibody, Rabies, Post-exposure prophylaxis
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.
Interventions
BIOLOGICALRabies virus-specific monoclonal antibodies
CL184 20 IU/kg intramuscularly on Day 0.
BIOLOGICALhuman polyclonal rabies immune globulin (HRIG)
HRIG 20 IU/kg intramuscularly on Day 0.
BIOLOGICALPlacebo
Placebo intramuscularly on Day 0.
BIOLOGICALHuman diploid cell vaccine (HDCV)
Rabies vaccine (HDCV) given on Days 0, 3, 7, 14, and 28.
BIOLOGICALPurified verocell rabies vaccine (PVRV)
Rabies vaccine (PVRV) given on Days 0, 3, 7, 14, and 28.
Sponsors
Crucell Holland BV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Rabies virus neutralizing activity | 90 days |
Countries
India
Outcome results
None listed