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

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT00289211
First received: February 7, 2006
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary 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 ]
    Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug 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.


Secondary Outcome Measures:
  • Number of Subjects With Beginning of Substantial Relief of the Defining Symptom [ Time Frame: Within 4 hours after initial treatment ] [ Designated as safety issue: No ]
    Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug 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 Complete Resolution of the HAE Attack [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Randomized subjects were contacted 72-96 hours (3-4 days) after discharge from the study site to determine when complete resolution of the HAE attack occurred.

  • Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion ] [ Designated as safety issue: No ]
    Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.

  • Functional C1INH Serum Levels [ Time Frame: Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion ] [ Designated as safety issue: No ]

    Percent change in functional C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded 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-, 2-, 4-, and 12 hours post-infusion ] [ Designated as safety issue: No ]
    Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.


Enrollment: 83
Study Start Date: June 2005
Study Completion Date: September 2007
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: C1INH-nf
1,000 Units (U) of C1INH-nf administered intravenously (IV). 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)
Placebo Comparator: Placebo
Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered.
Drug: Placebo (saline)

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

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00289211

  Show 37 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: NCT00289211     History of Changes
Other Study ID Numbers: LEVP2005-1/Part A
Study First Received: February 7, 2006
Results First Received: March 17, 2010
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:
Hereditary angioedema
HAE
C1 esterase inhibitor (human)
C1INH-nf

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 August 28, 2014