A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
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.
Biological: C1 inhibitor (human) [C1 INH]
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|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|
- 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 [ Time Frame: 12 to 24 weeks at each dose level ] [ Designated as safety issue: Yes ]Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
- Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates [ Time Frame: 12 weeks at each dose level ] [ Designated as safety issue: No ]
Two definitions of success were applied in this study:
- 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.
- 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.
- Use of Rescue Therapy and/or Other Therapy for Treatment of HAE Symptoms [ Time Frame: 12 weeks at each dose level ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Study Completion Date:||May 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
There were 3 potential dose escalation steps:
Biological: C1 inhibitor (human) [C1 INH]
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.
|United States, Arizona|
|Allergy, Asthma and Immunology Associates|
|Scottsdale, Arizona, United States, 85251|
|United States, Georgia|
|Family Allergy and Asthma Center|
|Atlanta, Georgia, United States, 30342|
|United States, Maryland|
|Institute for Asthma and Allergy|
|Wheaton, Maryland, United States, 20902|
|United States, New York|
|Winthrop University Hospital|
|Mineola, New York, United States, 11501|
|United States, Ohio|
|University of Cincinnati Medical Center|
|Cincinnati, Ohio, United States, 45267|
|United States, Oregon|
|Allergy and Asthma Research Group|
|Eugene, Oregon, United States, 97401|
|Baker Allergy, Asthma and Dermatology Research Center|
|Lake Oswego, Oregon, United States, 97035|
|United States, Tennessee|
|East Tennessee Center for Clinical Research|
|Knoxville, Tennessee, United States, 37909|
|United States, Texas|
|Bryan, Texas, United States, 77802|
|AARA Research Center|
|Dallas, Texas, United States, 75231|
|United States, Washington|
|Marycliff Allergy Specialist|
|Spokane, Washington, United States, 99204|
|Study Director:||Jennifer Schranz, MD, FRCP(C)||ViroPharma|