Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks (CHANGE 3)

LEVP2006-4 CHANGE 3 Trial (C1-Inhibitor in Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): Open-Label Use of C1INH-nf (Human) for the Prophylactic Treatment to Prevent HAE Attacks and as Treatment in Acute HAE Attacks

The study objective was to evaluate the safety and efficacy of prophylactic use of C1INH-nf for the prevention of acute HAE attacks.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Biological: C1 esterase inhibitor [human] (C1INH-nf)

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Hoover, Alabama, United States, 35216
      • Clinical Research Consultants, Inc
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy and Immunology Associates
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Allergy and Asthma Clinic of Northwest Arkansas
  • California
    • Los Angeles, California, United States, 90095
      • UCLA-David Geffen School of Medicine
    • San Diego, California, United States, 92093
      • University of California, San Diego
    • San Jose, California, United States, 95117
      • Allergy and Asthma Associates of Santa Clara
    • Walnut Creek, California, United States, 94598
      • Allergy and Asthma Clinical Research, Inc
  • Florida
    • Fort Lauderdale, Florida, United States, 33334
      • Allergy and Asthma Center
    • Orlando, Florida, United States, 32826
      • Allergy and Asthma Center of East Orlando
    • Weston, Florida, United States, 33331
      • Cleveland Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy and Asthma Center
    • Suwanee, Georgia, United States, 30024
      • Atlanta Allergy and Asthma Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University Consultants in Allergy & Immunology
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Welborn Clinic
  • Kansas
    • Liberal, Kansas, United States, 67901
      • Private Practice
    • Olathe, Kansas, United States, 66061
      • Olathe Medical Center
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves-Gilbert Clinic
    • Louisville, Kentucky, United States, 40215
      • Family Asthma and Allergy Research Center
  • Maryland
    • Waldorf, Maryland, United States, 20602
      • Asthma Allergy and Sinus Center
    • Wheaton, Maryland, United States, 20902
      • Institute for Asthma and Allergy
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Grand Traverse Allergy
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Clinical Research
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis University School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Nevada Access to Research and Education Society
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ Asthma and Allergy Research Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Hastings-on-Hudson, New York, United States, 10706
      • Private Practice
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Allergy Partners of East Carolina
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Legacy Pharma Research
    • Fargo, North Dakota, United States, 58122
      • MeritCare Clinical Research
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Childrens Hospital Clinical Research
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Allergy Clinic of Tulsa
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Medical Group
    • Lake Oswego, Oregon, United States, 97035
      • Allergy Asthma and Dermatology Research Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Galveston, Texas, United States, 77555-1083
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • University of Texas - Pediatric Pulmonary/Allergy and Immunology
    • San Antonio, Texas, United States, 78229
      • Allergy and Asthma Research Center
    • Woodville, Texas, United States, 75979
      • Tyler County Hospital
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Virginia Adult and Pediatric Allergy and Asthma
  • Washington
    • Spokane, Washington, United States, 99204
      • Marycliff Allergy Specialists
    • Tacoma, Washington, United States, 98405
      • Puget Sound Allergy, Asthma and Immunology
  • West Virginia
    • Parkersburg, West Virginia, United States, 26102
      • St. Joseph's Hospital/Cornerstone Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- History of at least 1 HAE attack per month or any history of laryngeal edema

In addition, this study was open to all subjects who:

• Completed participation in LEVP2005-1/B (NCT01005888) any time after the final prophylactic therapy in Part B
• Were enrolled but not randomized in LEVP2005-1/A (NCT00289211) after Part A was closed
• Were enrolled and randomized in LEVP2005-1/A after LEVP2005-1/B was closed to enrollment, any time after the 3-day telephone follow-up

• Were excluded from LEVP2005-1 for any of the following reasons:

  • Pregnancy or lactation
  • Age less than 6 years
  • Narcotic addiction
  • Presence of anti-C1 inhibitor (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 other than those sponsored by Lev Pharmaceuticals
• Received blood or a blood product in the past 60 days other than C1INH-nf

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-label C1INH-nf; 1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 7 days.	Biological: C1 esterase inhibitor [human] (C1INH-nf)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of All HAE Attacks	A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema.	Duration of the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antigenic C1 Inhibitor (C1INH) Serum Levels	Change from pre-infusion to 1 hour post-infusion in antigenic C1INH serum levels.	Pre-infusion to 1 hour post-infusion
Functional C1INH Serum Levels	Change from pre-infusion to 1 hour post-infusion in functional C1INH serum levels. 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
Complement C4 Serum Levels	Change from pre-infusion to 1 hour post-infusion in complement C4 serum levels.	Pre-infusion to 1 hour post-infusion

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2006
• Primary Completion (Actual): March 31, 2009
• Study Completion (Actual): March 31, 2009

Study Registration Dates

• First Submitted: April 17, 2007
• First Submitted That Met QC Criteria: April 17, 2007
• First Posted (Estimate): April 19, 2007

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hereditary angioedema; C1 esterase inhibitor (human)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins; Complement C1s
• Other Study ID Numbers: LEVP2006-4