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

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

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema Types I and II
• Intervention / Treatment: Biological: Berinert; Biological: CSL830

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: CSL Behring

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: December 24, 2012
• First Submitted That Met QC Criteria: January 2, 2013
• First Posted (Estimate): January 4, 2013

Study Record Updates

• Last Update Posted (Estimate): April 5, 2013
• Last Update Submitted That Met QC Criteria: April 4, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
• Other Study ID Numbers: CSL830_1001; 2012-002429-31 (EudraCT Number)