Clinical trial NCT01005888: C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: Hereditary angioedema
HAE
C1 esterase inhibitor (human)
C1INH-nf
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-11-01
Enrollment: 26
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Subject Withdrawals During Each Prophylactic Therapy Period
timeFrame: 12 weeks
measure: Average Severity of HAE Attacks During Each Prophylactic Therapy Period
timeFrame: 12 weeks
measure: Average Duration of HAE Attacks During Each Prophylactic Therapy Period
timeFrame: 12 weeks
measure: Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period
timeFrame: 12 weeks
measure: Antigenic C1 Inhibitor (C1INH) Serum Levels
timeFrame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
measure: Functional C1INH Serum Levels
timeFrame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12
Other outcomes:
measure: Total Number of Days of Swelling During Each Prophylactic Therapy Period
timeFrame: 12 weeks
Locations:
city: Scottsdale
country: United States
facility: Allergy and Immunology Associates
state: Arizona
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research, Inc
state: California
city: Suwanee
country: United States
facility: Atlanta Allergy and Asthma Clinic
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Health Research Institute
state: Hawaii
city: Evansville
country: United States
facility: Welborn Clinic Allergy and Immunology
state: Indiana
city: Lake Charles
country: United States
facility: Lake Charles Memorial Hospital
state: Louisiana
city: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Libby
country: United States
facility: Libby Clinic
state: Montana
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Columbus
country: United States
facility: Nationwide Childrens Hospital Clinical Research
state: Ohio
city: Tulsa
country: United States
facility: Allergy Clinic of Tulsa
state: Oklahoma
city: Lake Oswego
country: United States
facility: Allergy Asthma and Dermatology Research Center
state: Oregon
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Woodville
country: United States
facility: Tyler County Hospital
state: Texas
city: Parkersburg
country: United States
facility: St. Joseph's Hospital/Cornerstone Healthcare
state: West Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
citation: Lumry WR, Miller DP, Newcomer S, Fitts D, Dayno J. Quality of life in patients with hereditary angioedema receiving therapy for routine prevention of attacks. Allergy Asthma Proc. 2014 Sep-Oct;35(5):371-6. doi: 10.2500/aap.2014.35.3783.
citation: Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013 May;162(5):1017-22.e1-2. doi: 10.1016/j.jpeds.2012.11.030. Epub 2013 Jan 11.
citation: Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, Craig T, Grant JA, Hurewitz D, Bielory L, Cartwright WE, Koleilat M, Ryan W, Schaefer O, Manning M, Patel P, Bernstein JA, Friedman RA, Wilkinson R, Tanner D, Kohler G, Gunther G, Levy R, McClellan J, Redhead J, Guss D, Heyman E, Blumenstein BA, Kalfus I, Frank MM. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):513-22. doi: 10.1056/NEJMoa0805538.