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

Hereditary Angioedema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005888
• Other study ID #: LEVP2005-1/Part B
• Status: Completed
• Phase: Phase 3
• Start date: March 14, 2005
• Est. completion date: August 22, 2007

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 determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.

Description:

Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).

The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).

A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed to placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: August 22, 2007
• Est. primary completion date: August 22, 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Documented HAE

• Normal C1q level

• Relatively frequent angioedema attacks (at least 2 per month on average)

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	Nationwide Childrens Hospital Clinical Research	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Welborn Clinic Allergy and Immunology	Evansville	Indiana
United States	Hawaii Pacific Health Research Institute	Honolulu	Hawaii
United States	Lake Charles Memorial Hospital	Lake Charles	Louisiana
United States	Allergy Asthma and Dermatology Research Center	Lake Oswego	Oregon
United States	Libby Clinic	Libby	Montana
United States	Mount Sinai School of Medicine	New York	New York
United States	St. Joseph's Hospital/Cornerstone Healthcare	Parkersburg	West Virginia
United States	University of California, San Diego	San Diego	California
United States	Allergy and Immunology Associates	Scottsdale	Arizona
United States	Atlanta Allergy and Asthma Clinic	Suwanee	Georgia
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	Tyler County Hospital	Woodville	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Number of Days of Swelling During Each Prophylactic Therapy Period	A day of swelling was defined as a day that a subject reported swelling at any of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity).	12 weeks
Primary	Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period	An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period).	12 weeks
Secondary	Number of Subject Withdrawals During Each Prophylactic Therapy Period	At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record.	12 weeks
Secondary	Average Severity of HAE Attacks During Each Prophylactic Therapy Period	All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period.	12 weeks
Secondary	Average Duration of HAE Attacks During Each Prophylactic Therapy Period	The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of "no swelling" at all five locations.	12 weeks
Secondary	Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period	The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures.	12 weeks
Secondary	Antigenic C1 Inhibitor (C1INH) Serum Levels	Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits.	Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
Secondary	Functional C1INH Serum Levels	Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH).	Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12