Clinical trial NCT00289211: C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
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
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: 2006-02-09
Enrollment: 83
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to Beginning of Substantial Relief of the Defining Symptom
timeFrame: Within 4 hours after initial treatment
Secondary outcomes:
measure: Number of Subjects With Beginning of Substantial Relief of the Defining Symptom
timeFrame: Within 4 hours after initial treatment
measure: Time to Complete Resolution of the HAE Attack
timeFrame: 72 hours
measure: Antigenic C1 Inhibitor (C1INH) Serum Levels
timeFrame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
measure: Functional C1INH Serum Levels
timeFrame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
measure: Complement C4 Serum Levels
timeFrame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion
Other outcomes:
Locations:
city: Hoover
country: United States
facility: Clinical Research Consultants, Inc
state: Alabama
city: Scottsdale
country: United States
facility: Allergy and Immunology Associates
state: Arizona
city: Los Angeles
country: United States
facility: UCLA-David Geffen School of Medicine
state: California
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: Fort Lauderdale
country: United States
facility: Allergy and Asthma Center
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Healthcare
state: Florida
city: Atlanta
country: United States
facility: Family Allergy and Asthma Center
state: Georgia
city: Evansville
country: United States
facility: Welborn Clinic Allergy and Immunology
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinic
state: Iowa
city: Baton Rouge
country: United States
facility: The Baton Rouge Clinic, AMC
state: Louisiana
city: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Falmouth
country: United States
facility: Allergy Asthma and Immunology
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Traverse City
country: United States
facility: Grand Traverse Allergy
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Access to Research and Education Society
state: Nevada
city: Newark
country: United States
facility: UMDNJ Asthma and Allergy Research Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fargo
country: United States
facility: MeritCare Clinical Research
state: North Dakota
city: Cincinnati
country: United States
facility: Bernstein Clinical Research
state: Ohio
city: Columbus
country: United States
facility: Optimed 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: Hershey
country: United States
facility: Penn State University
state: Pennsylvania
city: Greenville
country: United States
facility: Allergy Partners of the Upstate
state: South Carolina
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Allergy and Asthma Research Center
state: Texas
city: Richmond
country: United States
facility: Virginia Adult and Pediatric Allergy and Asthma
state: Virginia
city: Spokane
country: United States
facility: Marycliff Allergy Specialists
state: Washington
city: Tacoma
country: United States
facility: Puget Sound Allergy, Asthma and Immunology
state: Washington
city: Madison
country: United States
facility: Allergy, Asthma and Pulmonary Clinical Research
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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: Grant JA, White MV, Li HH, Fitts D, Kalfus IN, Uknis ME, Lumry WR. Preprocedural administration of nanofiltered C1 esterase inhibitor to prevent hereditary angioedema attacks. Allergy Asthma Proc. 2012 Jul-Aug;33(4):348-53. doi: 10.2500/aap.2012.33.3585.
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.