Clinical trial NCT00438815: Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema
Keywords: Hereditary angioedema
C1 esterase inhibitor (human)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-02-22
Enrollment: 113
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
timeFrame: Duration of the study (2.5 years)
measure: Percent of HAE Attacks With Substantial Relief of the Defining Symptom
timeFrame: Within 4 hours after initial treatment
Secondary outcomes:
measure: Time to Beginning of Substantial Relief of the Defining Symptom
timeFrame: Within 4 hours after initial treatment
measure: Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
timeFrame: Within 4 hours after initial treatment
measure: Antigenic C1 Inhibitor (C1INH) Serum Levels
timeFrame: Pre-infusion to 1 hour post-infusion
measure: Functional C1INH Serum Levels
timeFrame: Pre-infusion to 1 hour post-infusion
measure: Complement C4 Serum Levels
timeFrame: Pre-infusion to 1 hour post-infusion
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Allergy and Immunology Associates
state: Arizona
city: Bentonville
country: United States
facility: Allergy and Asthma Clinic of Northwest Arkansas
state: Arkansas
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: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
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: Bemidji
country: United States
facility: MeritCare Clinical Research
state: Minnesota
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: Fargo
country: United States
facility: MeritCare Clinical Research
state: North Dakota
city: Centerville
country: United States
facility: Allergy & Asthma Centre of Dayton
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: Spokane
country: United States
facility: Marycliff Allergy Specialists
state: Washington
city: Parkersburg
country: United States
facility: Cornerstone Healthcare
state: West Virginia
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Baker JW, Craig TJ, Riedl MA, Banerji A, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1 esterase inhibitor (human) for hereditary angioedema attacks in pregnant women. Allergy Asthma Proc. 2013 Mar-Apr;34(2):162-9. doi: 10.2500/aap.2013.34.3645.
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: Riedl MA, Hurewitz DS, Levy R, Busse PJ, Fitts D, Kalfus I. Nanofiltered C1 esterase inhibitor (human) for the treatment of acute attacks of hereditary angioedema: an open-label trial. Ann Allergy Asthma Immunol. 2012 Jan;108(1):49-53. doi: 10.1016/j.anai.2011.10.017. Epub 2011 Nov 21.
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.