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

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT00438815
First received: February 21, 2007
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Hereditary Angioedema
Biological: C1 esterase inhibitor [human] (C1INH-nf)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf [ Time Frame: Duration of the study (2.5 years) ] [ Designated as safety issue: No ]
  • Percent of HAE Attacks With Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to Beginning of Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    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.

  • Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    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.

  • Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ] [ Designated as safety issue: No ]
    Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.

  • Functional C1INH Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ] [ Designated as safety issue: No ]

    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).


  • Complement C4 Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ] [ Designated as safety issue: No ]
    Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.


Enrollment: 113
Study Start Date: September 2006
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438815

  Show 30 Study Locations
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Bruce Zuraw, MD University of California, San Diego
  More Information

No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Chief Scientific Officer, ViroPharma
ClinicalTrials.gov Identifier: NCT00438815     History of Changes
Other Study ID Numbers: LEVP2006-1
Study First Received: February 21, 2007
Results First Received: March 31, 2010
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:
Hereditary angioedema
C1 esterase inhibitor (human)

Additional relevant MeSH terms:
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1s
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014