Back to resultsA Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
Primary Purpose
Hereditary Angioedema
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
C1 inhibitor (human) [C1 INH]
Sponsored by
About this trial
This is an interventional prevention trial for Hereditary Angioedema
Eligibility Criteria
Inclusion Criteria:
To be eligible for this protocol, subjects must:
- Be ≥6 years of age and ≥25 kg body weight.
Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
- C1 INH gene mutation
- C4 level below the lower limit of the reference range
- C1 INH antigen level below the lower limit of the reference range
- Functional C1 INH level below the lower limit of the reference range
- Family history of HAE (i.e., grandparent, parent, sibling)
- Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
OR
- If a child, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).
Exclusion Criteria:
To be eligible for this protocol, subjects must not:
- Have, as determined by the investigator and/or the sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
- Have a history of abnormal blood clotting or other coagulopathy.
- Be taking prescription anticoagulant medication.
- Have a history of allergic reaction to CINRYZE or other blood products.
- Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
- Have received any blood products (other than CINRYZE) within 60 days prior to screening.
Have any of the following laboratory values at screening:
- Hemoglobin <8 g/dL
- White blood cell count <2 x 10^9/L or >20 x 10^9/L
- Platelet count <50 x 10^9/L or >400 x 10^9/L
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.0 x the upper limit of normal
- Blood urea nitrogen and/or creatinine >2.0 x the upper limit of normal
- Be pregnant or breastfeeding.
Sites / Locations
- Allergy, Asthma and Immunology Associates
- Family Allergy and Asthma Center
- Institute for Asthma and Allergy
- Winthrop University Hospital
- University of Cincinnati Medical Center
- Allergy and Asthma Research Group
- Baker Allergy, Asthma and Dermatology Research Center
- East Tennessee Center for Clinical Research
- AARA Research Center
- Marycliff Allergy Specialist
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CINRYZE
Arm Description
There were 3 potential dose escalation steps: Step 1: 1500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks Step 2: 2000 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks Step 3: 2500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
Outcomes
Primary Outcome Measures
Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
Secondary Outcome Measures
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Two definitions of success were applied in this study: 1) Per-protocol success - Average angioedema attack rate of ≤1.0 per month at the end of any dose escalation step (Week 12). The a priori definition of study success was 4 or more subjects with per-protocol success. 2) Investigator-determined success - Based on the investigator's clinical judgment, an average monthly angioedema attack rate demonstrating improvement sufficient for progression to follow-up. In addition, subjects who were not a per-protocol or investigator-determined success, but who experienced a reduction of >1.0 attack per month from their historical angioedema attack rate at the end of any dose escalation step (Week 12), were summarized.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00914966
Brief Title
A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
Official Title
A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
August 31, 2009 (Actual)
Primary Completion Date
May 24, 2012 (Actual)
Study Completion Date
May 24, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objectives of the study were:
To assess the safety and tolerability of escalating doses of CINRYZE.
To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
To assess the immunogenicity of CINRYZE.
Detailed Description
Qualifying subjects entered a 3-step dose escalation algorithm:
Step 1: 1500 Units twice per week (starting dosing regimen for all subjects in the study)
Step 2: 2000 Units twice per week
Step 3: 2500 Units twice per week
Each step consisted of 12 weeks of safety monitoring, followed by calculation of average monthly angioedema attack rate based on subject reports of angioedema symptoms (regardless of intensity) and actual duration of therapy for that step.
If a subject was deemed a "success" at a given step and the investigator and medical monitor determined that it was safe for the subject to continue on that dose, the subject entered a 3 month follow-up period at that dose level with continued safety monitoring. The subject could not re-enter the study for purposes of dose escalation during the follow-up period.
If a subject was not deemed a "success," the subject initiated the next highest step of the dose escalation algorithm provided that the investigator and medical monitor agreed that dose escalation was appropriate. If at the end of Step 3 (2500 Units), a subject was not deemed a "success," then the Week 12 visit represented study completion and the subject was referred to the physician who manages their HAE care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CINRYZE
Arm Type
Experimental
Arm Description
There were 3 potential dose escalation steps:
Step 1: 1500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
Step 2: 2000 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
Step 3: 2500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
Intervention Type
Biological
Intervention Name(s)
C1 inhibitor (human) [C1 INH]
Other Intervention Name(s)
CINRYZE, C1 esterase inhibitor (human)
Primary Outcome Measure Information:
Title
Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
Description
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
Time Frame
12 to 24 weeks at each dose level
Secondary Outcome Measure Information:
Title
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Description
Two definitions of success were applied in this study: 1) Per-protocol success - Average angioedema attack rate of ≤1.0 per month at the end of any dose escalation step (Week 12). The a priori definition of study success was 4 or more subjects with per-protocol success. 2) Investigator-determined success - Based on the investigator's clinical judgment, an average monthly angioedema attack rate demonstrating improvement sufficient for progression to follow-up. In addition, subjects who were not a per-protocol or investigator-determined success, but who experienced a reduction of >1.0 attack per month from their historical angioedema attack rate at the end of any dose escalation step (Week 12), were summarized.
Time Frame
12 weeks at each dose level
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
To be eligible for this protocol, subjects must:
Be ≥6 years of age and ≥25 kg body weight.
Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
C1 INH gene mutation
C4 level below the lower limit of the reference range
C1 INH antigen level below the lower limit of the reference range
Functional C1 INH level below the lower limit of the reference range
Family history of HAE (i.e., grandparent, parent, sibling)
Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
OR
If a child, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).
Exclusion Criteria:
To be eligible for this protocol, subjects must not:
Have, as determined by the investigator and/or the sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
Have a history of abnormal blood clotting or other coagulopathy.
Be taking prescription anticoagulant medication.
Have a history of allergic reaction to CINRYZE or other blood products.
Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
Have received any blood products (other than CINRYZE) within 60 days prior to screening.
Have any of the following laboratory values at screening:
Hemoglobin <8 g/dL
White blood cell count <2 x 10^9/L or >20 x 10^9/L
Platelet count <50 x 10^9/L or >400 x 10^9/L
Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.0 x the upper limit of normal
Blood urea nitrogen and/or creatinine >2.0 x the upper limit of normal
Be pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Allergy, Asthma and Immunology Associates
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Family Allergy and Asthma Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Institute for Asthma and Allergy
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Allergy and Asthma Research Group
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Baker Allergy, Asthma and Dermatology Research Center
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
East Tennessee Center for Clinical Research
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
City
Bryan
State/Province
Texas
ZIP/Postal Code
77802
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Marycliff Allergy Specialist
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
12. IPD Sharing Statement
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A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
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