A Study to Evaluate the Safety and Pharmacokinetics of Two Formulations of C1-esterase Inhibitor

Study Overview
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Brief Summary
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A new formulation of Berinert (CSL830) is being investigated for the management of hereditary angioedema (HAE). The main aim of the study is to assess the safety of a single 1500 IU dose of the new formulation of Berinert. This study will also look at the pharmacokinetics of CSL830 relative to Berinert currently on the market.

Official Title
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A Randomized, Double-blind, Single-center, Cross-over Study to Evaluate the Safety, Bioavailability and Pharmacokinetics of Two Formulations of C1-esterase Inhibitor Administered Intravenously

Conditions
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Hereditary Angioedema Types I and II

Intervention / Treatment
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* Biological: Berinert
* Biological: CSL830


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects without clinically significant medical conditions or laboratory abnormalities Male or female subjects aged 18 to 45 years inclusive, at the time of informed consent Non-smokers Body mass index of 18.0 to 29.0 kg/m2 inclusive Exclusion Criteria: Previous history of clinically significant arterial or venous thrombosis, current history of a clinically significant pro-thrombotic risk, or a clinically significant abnormality on laboratory thrombotic screen at the screening visit. Known or suspected hypersensitivity to the investigational medicinal product (IMP), or to any excipients of the IMP. Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (ie, estrogen/progesterone containing products) within 3 months before the screening visit. Alcohol, drug, or medication abuse within one year before the study. Female subjects of childbearing potential (eg, not post-menopausal) either not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study, or have a vasectomized partner, or not sexually abstinent for the entire duration of the study, or not surgically sterile. Participation in another clinical study (or use of another IMP) within 30 days (or 5 times the half-life, whichever is longer) before, or during, the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berinert, then CSL830<br>A single intravenous dose of Berinert at 1500 units (1500 IU), followed by a single intravenous dose of CSL830 at 1500 IU. | Biological: Berinert<br>* Berinert is a plasma-derived C1 esterase inhibitor (human), supplied as a freeze-dried powder for reconstitution.<br>Biological: CSL830<br>* CSL830 is a formulation of Berinert.<br>|
| Experimental: CSL830, then Berinert<br>A single intravenous dose of CSL830 at 1500 IU, followed by a single intravenous dose of Berinert at 1500 IU. | Biological: Berinert<br>* Berinert is a plasma-derived C1 esterase inhibitor (human), supplied as a freeze-dried powder for reconstitution.<br>Biological: CSL830<br>* CSL830 is a formulation of Berinert.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) within 24 hours of CSL830 infusion |  | From the start of infusion to 24 hours after the end of infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) within 10 days of the CSL830 infusion |  | From the start of infusion to 10 days after the infusion | 
| Relative bioavailability of CSL830 versus Berinert - Cmax | Relative bioavailability in terms of maximum concentration (Cmax) of CSL830 versus Berinert | 240 hours | 
| Relative bioavailability of CSL830 versus Berinert - AUC | Relative bioavailability in terms of area under the curve from timepoint 0 to infinity (AUC0-∞) of CSL830 versus Berinert | 240 hours |