Clinical trial NCT01576523: A Study to Evaluate the Clinical Pharmacology and Safety of C1-esterase Inhibitor Administered by the Subcutaneous Route
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hereditary Angioedema Types I and II
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2012-04-12
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Modeled C1-esterase Inhibitor Functional Activity Trough Level
timeFrame: at the fourth week of each dosing regimen
Secondary outcomes:
measure: As-observed C1-esterase Inhibitor Functional Activity Trough Level
timeFrame: during the last week of 4-week dose regimen
measure: C1-esterase Inhibitor Concentration Trough Level
timeFrame: during the last week of 4-week dose regimen
measure: C4 Concentration Trough Level
timeFrame: during the last week of 4-week dose regimen
measure: Change From Baseline in C1-esterase Inhibitor Functional Activity
timeFrame: Baseline and during the last week of 4-week dose regimen
measure: Change From Baseline in C1-esterase Inhibitor Concentration
timeFrame: Baseline and during the last week of 4-week dose regimen
measure: Change From Baseline in C4 Concentration
timeFrame: Baseline and during the last week of 4-week dose regimen
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Study Site
state: Georgia
city: Chevy Chase
country: United States
facility: Study Site
state: Maryland
city: Cincinnati
country: United States
facility: Study Site
state: Ohio
city: Toledo
country: United States
facility: Study Site
state: Ohio
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Berlin
country: Germany
facility: Study Site
city: Frankfurt
country: Germany
facility: Study Site
city: Mainz
country: Germany
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Global Clinical Program Director
role: STUDY_DIRECTOR
References:
citation: 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.