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

Purpose

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	Intervention	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 Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: hereditary angioedema

Drug Information available for: SERPING1 protein, human

U.S. FDA Resources

Further study details as provided by CSL Behring:

Primary Outcome Measures:

Modeled C1-esterase inhibitor functional activity trough level [ Time Frame: 13 time points during each 4-week dose regimen ] [ Designated as safety issue: No ]
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation

Secondary Outcome Measures:

C1-esterase inhibitor functional activity trough level [ Time Frame: 2 time points during the last week of each 4-week dose regimen ] [ Designated as safety issue: No ]
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
C1-esterase inhibitor concentration trough level [ Time Frame: 2 time points during the last week of each 4-week dose regimen ] [ Designated as safety issue: No ]
Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
C4 concentration trough level [ Time Frame: 2 time points during the last week of each 4-week dose regimen ] [ Designated as safety issue: No ]
Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
Change in C1-esterase inhibitor functional activity [ Time Frame: After four weeks of treatment with each dose regimen ] [ Designated as safety issue: No ]
Mean change from baseline of C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
Change in C1-esterase inhibitor concentration [ Time Frame: After four weeks of treatment with each dose regimen ] [ Designated as safety issue: No ]
Mean change from baseline of C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
Change in C4 concentration [ Time Frame: After four weeks of treatment with each dose regimen ] [ Designated as safety issue: No ]
Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens

Enrollment:	18
Study Start Date:	April 2012
Study Completion Date:	December 2012
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01576523

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

No publications provided

Responsible Party:	CSL Behring
ClinicalTrials.gov Identifier:	NCT01576523 History of Changes
Other Study ID Numbers:	CSL830_2001, 2011-005013-36
Study First Received:	April 10, 2012
Last Updated:	January 17, 2013
Health Authority:	United States: Food and Drug Administration

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

Genetic Diseases, Inborn
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1
Complement C1s
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013