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

Phase 1

Completed

• Conditions: Hereditary Angioedema Types I and II
• Interventions: Biological: C1-esterase inhibitor - single intravenous dose; Biological: C1-esterase inhibitor - subcutaneous medium dose; Biological: C1-esterase inhibitor - subcutaneous low dose; Biological: C1-esterase inhibitor - subcutaneous high dose

• Registration Number: NCT01576523
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-04
• Study First Submitted: 2012-04-10
• Study First Submitted QC: 2012-04-10
• Study First Posted: 2012-04-12
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Disposition First Submitted: 2014-01-28
• Disposition First Submitted QC: 2014-01-28
• Disposition First Posted: 2014-02-28
• Results First Submitted: 2020-12-11
• Status Verified: 2021-01
• Results First Submitted QC: 2021-01-29
• Last Update Submitted: 2021-01-29
• Results First Posted: 2021-02-01
• Last Update Posted: 2021-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Low, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous high dose	-
High, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous medium dose	-
Medium, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
Low, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
Low, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous low dose	-
Medium, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous high dose	-
Low, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous low dose	-
Low, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
Low, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous medium dose	-
Medium, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
Medium, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous low dose	-
Medium, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous medium dose	-
Medium, then high, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous medium dose	-
High, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
High, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous low dose	-
High, then low, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous high dose	-
High, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - single intravenous dose	-
High, then medium, C1-esterase inhibitor dose	C1-esterase inhibitor - subcutaneous high dose	-

Primary Outcome Measures

Name	Time	Method
Modeled C1-esterase Inhibitor Functional Activity Trough Level	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

Name	Time	Method
As-observed C1-esterase Inhibitor Functional Activity Trough Level	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
C1-esterase Inhibitor Concentration Trough Level	during the last week of 4-week dose regimen	Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
C4 Concentration Trough Level	during the last week of 4-week dose regimen	Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
Change From Baseline in C1-esterase Inhibitor Functional Activity	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
Change From Baseline in C1-esterase Inhibitor Concentration	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
Change From Baseline in C4 Concentration	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

Trial Locations

Locations (1)

Study Site; 🇩🇪 Mainz, Germany