Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks (CHANGE 2)

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

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

Study Overview

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

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.

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • 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, 92093-0732
      • University of California, San Diego
    • 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, 32806
      • Orlando Regional Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy and Asthma Center
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Welborn Clinic Allergy and Immunology
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Institute for Asthma and Allergy
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Traverse City, Michigan, United States, 49684
      • Grand Traverse Allergy
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Clinical Research
  • 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
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • MeritCare Clinical Research
  • Ohio
    • Centerville, Ohio, United States, 45458
      • Allergy & Asthma Centre of Dayton
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Allergy Clinic of Tulsa
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Allergy Asthma and Dermatology Research Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Allergy Partners of the Upstate
  • 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
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Allergy and Asthma Research Center
  • Washington
    • Spokane, Washington, United States, 99204
      • Marycliff Allergy Specialists
  • West Virginia
    • Parkersburg, West Virginia, United States, 26101
      • Cornerstone Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

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. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.	Biological: C1 esterase inhibitor [human] (C1INH-nf)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf		Duration of the study (2.5 years)
Percent of HAE Attacks With Substantial Relief of the Defining Symptom	Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.	Within 4 hours after initial treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Beginning of Substantial Relief of the Defining Symptom	Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.	Within 4 hours after initial treatment
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments	For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or >4.0) was not possible.	Within 4 hours after initial treatment
Antigenic C1 Inhibitor (C1INH) Serum Levels	Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.	Pre-infusion to 1 hour post-infusion
Functional C1INH Serum Levels	Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).	Pre-infusion to 1 hour post-infusion
Complement C4 Serum Levels	Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.	Pre-infusion to 1 hour post-infusion

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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): September 21, 2006
• Primary Completion (ACTUAL): March 31, 2009
• Study Completion (ACTUAL): March 31, 2009

Study Registration Dates

• First Submitted: February 21, 2007
• First Submitted That Met QC Criteria: February 21, 2007
• First Posted (ESTIMATE): February 22, 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: LEVP2006-1