Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks

Hereditary Angioedema Clinical Trial

— CHANGE 2  

Official title:

LEVP2006-1 CHANGE 2 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Safety/Efficacy Repeat Exposure Study of C1INH-nf (Human) in the Treatment of Acute HAE Attacks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00438815
• Other study ID #: LEVP2006-1
• Status: Completed
• Phase: Phase 3
• Start date: September 21, 2006
• Est. completion date: March 31, 2009

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study objective was to evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.

Description:

A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 113
• Est. completion date: March 31, 2009
• Est. primary completion date: March 31, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

This study was open to all subjects who:

• Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up

• Completed participation in LEVP2005-1/B any time after the final prophylactic therapy in Part B

• Were enrolled but not randomized in LEVP2005-1/A after Part A was closed

• Were excluded from LEVP2005-1 for any of the following reasons:

• Pregnancy or lactation

• Age less than 6 years

• Narcotic addiction

• Presence of anti-C1INH autoantibodies

• Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances:

• Had a diagnosis of HAE: evidence of a low C4 level plus either a low C1INH antigenic level or a low C1INH functional level, or

• Had a known HAE-causing C1INH mutation, or

• Had a diagnosis of HAE based on a strong family history of HAE as determined by the principal investigator

Exclusion Criteria:

• History of allergic reaction to C1INH or other blood products

• Participated in any other investigational drug study within the past 30 days

• Received blood or a blood product in the past 60 days other than C1INH-nf

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Biological:
• C1 esterase inhibitor [human] (C1INH-nf)

Locations

Country	Name	City	State
United States	Family Allergy and Asthma Center	Atlanta	Georgia
United States	MeritCare Clinical Research	Bemidji	Minnesota
United States	Allergy and Asthma Clinic of Northwest Arkansas	Bentonville	Arkansas
United States	Montefiore Medical Center	Bronx	New York
United States	Allergy & Asthma Centre of Dayton	Centerville	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Welborn Clinic Allergy and Immunology	Evansville	Indiana
United States	MeritCare Clinical Research	Fargo	North Dakota
United States	Allergy and Asthma Center	Fort Lauderdale	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Allergy Partners of the Upstate	Greenville	South Carolina
United States	Penn State University	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Allergy Asthma and Dermatology Research Center	Lake Oswego	Oregon
United States	Nevada Access to Research and Education Society	Las Vegas	Nevada
United States	UCLA-David Geffen School of Medicine	Los Angeles	California
United States	Winthrop University Hospital	Mineola	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	UMDNJ Asthma and Allergy Research Center	Newark	New Jersey
United States	Orlando Regional Healthcare	Orlando	Florida
United States	Cornerstone Healthcare	Parkersburg	West Virginia
United States	Allergy and Asthma Research Center	San Antonio	Texas
United States	University of California, San Diego	San Diego	California
United States	Allergy and Immunology Associates	Scottsdale	Arizona
United States	Marycliff Allergy Specialists	Spokane	Washington
United States	Grand Traverse Allergy	Traverse City	Michigan
United States	Allergy Clinic of Tulsa	Tulsa	Oklahoma
United States	Allergy and Asthma Clinical Research, Inc	Walnut Creek	California
United States	Institute for Asthma and Allergy	Wheaton	Maryland
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf		Duration of the study (2.5 years)
Primary	Percent of HAE Attacks With Substantial Relief of the Defining Symptom	Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.	Within 4 hours after initial treatment
Secondary	Time to Beginning of Substantial Relief of the Defining Symptom	Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.	Within 4 hours after initial treatment
Secondary	Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments	For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or >4.0) was not possible.	Within 4 hours after initial treatment
Secondary	Antigenic C1 Inhibitor (C1INH) Serum Levels	Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.	Pre-infusion to 1 hour post-infusion
Secondary	Functional C1INH Serum Levels	Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).	Pre-infusion to 1 hour post-infusion
Secondary	Complement C4 Serum Levels	Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.	Pre-infusion to 1 hour post-infusion