A Study to Evaluate the Clinical Pharmacology and Safety of C1-esterase Inhibitor Administered by the Subcutaneous Route
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
2 other identifiers
interventional
18
2 countries
8
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2012
Shorter than P25 for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2012
CompletedFirst Submitted
Initial submission to the registry
April 10, 2012
CompletedFirst Posted
Study publicly available on registry
April 12, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedResults Posted
Study results publicly available
February 1, 2021
CompletedFebruary 1, 2021
January 1, 2021
8 months
April 10, 2012
December 11, 2020
January 29, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (6)
As-observed C1-esterase Inhibitor Functional Activity Trough Level
during the last week of 4-week dose regimen
C1-esterase Inhibitor Concentration Trough Level
during the last week of 4-week dose regimen
C4 Concentration Trough Level
during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Functional Activity
Baseline and during the last week of 4-week dose regimen
Change From Baseline in C1-esterase Inhibitor Concentration
Baseline and during the last week of 4-week dose regimen
- +1 more secondary outcomes
Study Arms (6)
Low, then medium, C1-esterase inhibitor dose
EXPERIMENTALMedium, then low, C1-esterase inhibitor dose
EXPERIMENTALMedium, then high, C1-esterase inhibitor dose
EXPERIMENTALLow, then high, C1-esterase inhibitor dose
EXPERIMENTALHigh, then low, C1-esterase inhibitor dose
EXPERIMENTALHigh, then medium, C1-esterase inhibitor dose
EXPERIMENTALInterventions
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.
A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CSL Behringlead
- Parexelcollaborator
Study Sites (8)
Study Site
Atlanta, Georgia, 30342, United States
Study Site
Chevy Chase, Maryland, 20815, United States
Study Site
Cincinnati, Ohio, 45231, United States
Study Site
Toledo, Ohio, 43617, United States
Study Site
Hershey, Pennsylvania, 19108, United States
Study Site
Berlin, 10117, Germany
Study Site
Frankfurt, 60596, Germany
Study Site
Mainz, 55101, Germany
Related 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 subcutaneous C1-inhibitor concentrate. Allergy. 2015 Oct;70(10):1319-28. doi: 10.1111/all.12658. Epub 2015 Aug 11.
PMID: 26016741RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- CSL Behring
Study Officials
- STUDY DIRECTOR
Global Clinical Program Director
CSL Behring
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2012
First Posted
April 12, 2012
Study Start
April 1, 2012
Primary Completion
December 1, 2012
Study Completion
December 1, 2012
Last Updated
February 1, 2021
Results First Posted
February 1, 2021
Record last verified: 2021-01