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

Hereditary Angioedema Clinical Trial

Official title:

LEVP2005-1/Part A: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) for the Treatment of HAE in Acute Attacks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00289211
• Other study ID #: LEVP2005-1/Part A
• Status: Completed
• Phase: Phase 3
• Start date: March 14, 2005
• Est. completion date: April 13, 2007

Study information

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

Clinical Trial Summary

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

Description:

Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary. The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures. A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: April 13, 2007
• Est. primary completion date: April 13, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Documented HAE
• Normal C1q level

Exclusion Criteria:

• Low C1q level
• B-cell malignancy
• Presence of anti-C1INH autoantibody
• History of allergic reaction to C1INH or other blood products
• Narcotic addiction
• Current participation in any other investigational drug study or within the past 30 days
• Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days
• Pregnancy or lactation
• Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

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

Drug:
• Placebo (saline)

Locations

Country	Name	City	State
United States	Family Allergy and Asthma Center	Atlanta	Georgia
United States	The Baton Rouge Clinic, AMC	Baton Rouge	Louisiana
United States	Montefiore Medical Center	Bronx	New York
United States	Bernstein Clinical Research	Cincinnati	Ohio
United States	Optimed Research	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Welborn Clinic Allergy and Immunology	Evansville	Indiana
United States	Allergy Asthma and Immunology	Falmouth	Massachusetts
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	Clinical Research Consultants, Inc	Hoover	Alabama
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa Hospital and Clinic	Iowa City	Iowa
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	Allergy, Asthma and Pulmonary Clinical Research	Madison	Wisconsin
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	Virginia Adult and Pediatric Allergy and Asthma	Richmond	Virginia
United States	St. Louis University School of Medicine	Saint Louis	Missouri
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	Puget Sound Allergy, Asthma and Immunology	Tacoma	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	Time to Beginning of Substantial Relief of the Defining Symptom	Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug 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	Number of Subjects With Beginning of Substantial Relief of the Defining Symptom	Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug 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 Complete Resolution of the HAE Attack	Randomized subjects were contacted 72-96 hours (3-4 days) after discharge from the study site to determine when complete resolution of the HAE attack occurred.	72 hours
Secondary	Antigenic C1 Inhibitor (C1INH) Serum Levels	Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.	Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Secondary	Functional C1INH Serum Levels	Percent change in functional C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded 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-, 2-, 4-, and 12 hours post-infusion
Secondary	Complement C4 Serum Levels	Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.	Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion