A Study to Evaluate the Clinical Pharmacology and Safety of C1-esterase Inhibitor Administered by the Subcutaneous Route

• ClinicalTrials.gov Identifier: NCT01576523
• Recruitment Status: Completed
• First Posted: April 12, 2012
• Results First Posted: February 1, 2021
• Last Update Posted: February 1, 2021
• Sponsor: CSL Behring
• Collaborator: Parexel
• Information provided by (Responsible Party): CSL Behring

Study Description

Brief Summary:

The aim of the study is to assess what happens to C1-esterase inhibitor that is administered under the skin of subjects with hereditary angioedema. Three different dosing regimens of C1-esterase inhibitor will be assessed. Each subject will be assigned to receive 2 of the 3 dosing regimens, each for 4 weeks. The activity and concentration of C1-esterase inhibitor in the blood will be measured during each 4-week period. The study will also examine how well C1-esterase inhibitor administered under the skin is tolerated by the subjects.

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema Types I and II	Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous medium dose; Biological: C1-esterase inhibitor - subcutaneous high dose	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: An Open-label, Cross-over, Dose-ranging Study to Evaluate the Pharmacokinetics, Pharmacodynamics and Safety of the Subcutaneous Administration of a Human Plasma-derived C1-esterase Inhibitor in Subjects With Hereditary Angioedema
• Study Start Date: April 2012
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Low, then medium, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous low dose; A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous medium dose; A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
Experimental: Medium, then low, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous low dose; A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous medium dose; A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
Experimental: Medium, then high, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous medium dose; A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous high dose; A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
Experimental: Low, then high, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous low dose; A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous high dose; A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
Experimental: High, then low, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous low dose; A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous high dose; A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
Experimental: High, then medium, C1-esterase inhibitor dose	Biological: C1-esterase inhibitor - single intravenous dose; A single intravenous dose of C1-esterase inhibitor (Berinert) at 20 units per kg body weight will be administered to all subjects prior to receiving the first dose of subcutaneous C1-esterase inhibitor.; Biological: C1-esterase inhibitor - subcutaneous medium dose; A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.; Biological: C1-esterase inhibitor - subcutaneous high dose; A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.

Outcome Measures

Primary Outcome Measures :

1. Modeled C1-esterase Inhibitor Functional Activity Trough Level [ Time Frame: at the fourth week of each dosing regimen ]
   Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation

Secondary Outcome Measures :

1. As-observed C1-esterase Inhibitor Functional Activity Trough Level [ Time Frame: during the last week of 4-week dose regimen ]
   Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
2. C1-esterase Inhibitor Concentration Trough Level [ Time Frame: during the last week of 4-week dose regimen ]
   Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
3. C4 Concentration Trough Level [ Time Frame: during the last week of 4-week dose regimen ]
   Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
4. Change From Baseline in C1-esterase Inhibitor Functional Activity [ Time Frame: Baseline and during the last week of 4-week dose regimen ]
   Mean change from baseline of C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
5. Change From Baseline in C1-esterase Inhibitor Concentration [ Time Frame: Baseline and during the last week of 4-week dose regimen ]
   Mean change from baseline of C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
6. Change From Baseline in C4 Concentration [ Time Frame: Baseline and during the last week of 4-week dose regimen ]
   Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males or females aged 18 years or older.
• Laboratory-confirmed hereditary angioedema type I or II.
• Less than two hereditary angioedema attacks per month in the last three months.
• Body weight of 50.0 kg to 110.0 kg.

Exclusion Criteria:

• Receiving prophylactic C1-esterase inhibitor therapy.
• Received C1-esterase inhibitor, ecallantide, icatibant or any blood products for the prevention or treatment of hereditary angioedema within 7 days before the screening visit.
• Intends to use recombinant C1-esterase inhibitor or fresh frozen plasma for the acute treatment of hereditary angioedema during the study.
• Received androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 30 days before the screening visit.
• Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progesterone-containing products) within 3 months prior to the screening visit.
• Known or suspected hypersensitivity to the study product, or to any excipients of the study product.
• Pregnancy or lactation.

Contacts and Locations

Locations

United States, Georgia

Study Site

Atlanta, Georgia, United States, 30342

United States, Maryland

Study Site

Chevy Chase, Maryland, United States, 20815

United States, Ohio

Study Site

Cincinnati, Ohio, United States, 45231

Study Site

Toledo, Ohio, United States, 43617

United States, Pennsylvania

Study Site

Hershey, Pennsylvania, United States, 19108

Germany

Study Site

Berlin, Germany, 10117

Study Site

Frankfurt, Germany, 60596

Study Site

Mainz, Germany, 55101

Sponsors and Collaborators

CSL Behring

Parexel

Investigators

• Study Director: Global Clinical Program Director; CSL Behring

More Information

Publications of Results:

Zuraw BL, Cicardi M, Longhurst HJ, Bernstein JA, Li HH, Magerl M, Martinez-Saguer I, Rehman SM, Staubach P, Feuersenger H, Parasrampuria R, Sidhu J, Edelman J, Craig T. Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1-inhibitor concentrate. Allergy. 2015 Oct;70(10):1319-28. doi: 10.1111/all.12658. Epub 2015 Aug 11.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT01576523
• Other Study ID Numbers: CSL830_2001; 2011-005013-36 ( EudraCT Number )
• First Posted: April 12, 2012
• Results First Posted: February 1, 2021
• Last Update Posted: February 1, 2021
• Last Verified: January 2021

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Complement C1s; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Immunosuppressive Agents