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

Hereditary Angioedema Types I and II Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01576523
• Other study ID #: CSL830_2001
• Secondary ID: 2011-005013-36
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2012
• Est. completion date: December 2012

Study information

• Verified date: January 2021
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema Types I and II

Intervention

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.
• C1-esterase inhibitor - subcutaneous low dose
A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
• C1-esterase inhibitor - subcutaneous medium dose
A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
• C1-esterase inhibitor - subcutaneous high dose
A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.

Locations

Country	Name	City	State
Germany	Study Site	Berlin
Germany	Study Site	Frankfurt
Germany	Study Site	Mainz
United States	Study Site	Atlanta	Georgia
United States	Study Site	Chevy Chase	Maryland
United States	Study Site	Cincinnati	Ohio
United States	Study Site	Hershey	Pennsylvania
United States	Study Site	Toledo	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
CSL Behring	Parexel

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (1)

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 subcuta — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modeled C1-esterase Inhibitor Functional Activity Trough Level	Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation	at the fourth week of each dosing regimen
Secondary	As-observed C1-esterase Inhibitor Functional Activity Trough Level	Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens	during the last week of 4-week dose regimen
Secondary	C1-esterase Inhibitor Concentration Trough Level	Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens	during the last week of 4-week dose regimen
Secondary	C4 Concentration Trough Level	Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens	during the last week of 4-week dose regimen
Secondary	Change From Baseline in C1-esterase Inhibitor Functional Activity	Mean change from baseline of C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens	Baseline and during the last week of 4-week dose regimen
Secondary	Change From Baseline in C1-esterase Inhibitor Concentration	Mean change from baseline of C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens	Baseline and during the last week of 4-week dose regimen
Secondary	Change From Baseline in C4 Concentration	Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens	Baseline and during the last week of 4-week dose regimen