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

Primary Purpose

Hereditary Angioedema Types I and II

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
C1-esterase inhibitor - single intravenous dose
C1-esterase inhibitor - subcutaneous low dose
C1-esterase inhibitor - subcutaneous medium dose
C1-esterase inhibitor - subcutaneous high dose
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hereditary Angioedema Types I and II

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site
  • Study Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Low, then medium, C1-esterase inhibitor dose

Medium, then low, C1-esterase inhibitor dose

Medium, then high, C1-esterase inhibitor dose

Low, then high, C1-esterase inhibitor dose

High, then low, C1-esterase inhibitor dose

High, then medium, C1-esterase inhibitor dose

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
C1-esterase Inhibitor Concentration Trough Level
Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
C4 Concentration Trough Level
Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
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
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
Change From Baseline in C4 Concentration
Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens

Full Information

First Posted
April 10, 2012
Last Updated
January 29, 2021
Sponsor
CSL Behring
Collaborators
Parexel
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1. Study Identification

Unique Protocol Identification Number
NCT01576523
Brief Title
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

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring
Collaborators
Parexel

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema Types I and II

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low, then medium, C1-esterase inhibitor dose
Arm Type
Experimental
Arm Title
Medium, then low, C1-esterase inhibitor dose
Arm Type
Experimental
Arm Title
Medium, then high, C1-esterase inhibitor dose
Arm Type
Experimental
Arm Title
Low, then high, C1-esterase inhibitor dose
Arm Type
Experimental
Arm Title
High, then low, C1-esterase inhibitor dose
Arm Type
Experimental
Arm Title
High, then medium, C1-esterase inhibitor dose
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
C1-esterase inhibitor - single intravenous dose
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
C1-esterase inhibitor - subcutaneous low dose
Intervention Description
A low dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
Intervention Type
Biological
Intervention Name(s)
C1-esterase inhibitor - subcutaneous medium dose
Intervention Description
A medium dose of C1-esterase inhibitor will be administered subcutaneously twice a week for four weeks.
Intervention Type
Biological
Intervention Name(s)
C1-esterase inhibitor - subcutaneous high dose
Intervention Description
A high dose of C1-esterase inhibitor will administered subcutaneously twice a week for four weeks.
Primary Outcome Measure Information:
Title
Modeled C1-esterase Inhibitor Functional Activity Trough Level
Description
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens, based on modeling and simulation
Time Frame
at the fourth week of each dosing regimen
Secondary Outcome Measure Information:
Title
As-observed C1-esterase Inhibitor Functional Activity Trough Level
Description
Mean trough C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
Time Frame
during the last week of 4-week dose regimen
Title
C1-esterase Inhibitor Concentration Trough Level
Description
Mean trough C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
Time Frame
during the last week of 4-week dose regimen
Title
C4 Concentration Trough Level
Description
Mean trough C4 concentration of the low, medium and high subcutaneous dose regimens
Time Frame
during the last week of 4-week dose regimen
Title
Change From Baseline in C1-esterase Inhibitor Functional Activity
Description
Mean change from baseline of C1-esterase inhibitor functional activity of the low, medium and high subcutaneous dose regimens
Time Frame
Baseline and during the last week of 4-week dose regimen
Title
Change From Baseline in C1-esterase Inhibitor Concentration
Description
Mean change from baseline of C1-esterase inhibitor concentration of the low, medium and high subcutaneous dose regimens
Time Frame
Baseline and during the last week of 4-week dose regimen
Title
Change From Baseline in C4 Concentration
Description
Mean change from baseline of C4 concentration of the low, medium and high subcutaneous dose regimens
Time Frame
Baseline and during the last week of 4-week dose regimen

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Program Director
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Study Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Study Site
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Study Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
Study Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
Study Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
19108
Country
United States
Facility Name
Study Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Study Site
City
Frankfurt
ZIP/Postal Code
60596
Country
Germany
Facility Name
Study Site
City
Mainz
ZIP/Postal Code
55101
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
26016741
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.
Results Reference
result

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

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