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

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT01005888
First received: October 29, 2009
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 prevention 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: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: LEVP2005-1/Part B: A Double-blind, Placebo-Controlled, Clinical Study to Investigate the Efficacy and Safety of Purified C1 Esterase Inhibitor (Human) as Prophylactic Treatment to Prevent HAE Attacks

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period).


Secondary Outcome Measures:
  • Number of Subject Withdrawals During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record.

  • Average Severity of HAE Attacks During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period.

  • Average Duration of HAE Attacks During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of "no swelling" at all five locations.

  • Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures.

  • Antigenic C1 Inhibitor (C1INH) Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
    Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits.

  • Functional C1INH Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]

    Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits.

    Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH).



Other Outcome Measures:
  • Total Number of Days of Swelling During Each Prophylactic Therapy Period [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    A day of swelling was defined as a day that a subject reported swelling at any of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity).


Enrollment: 26
Study Start Date: September 2005
Study Completion Date: August 2007
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: C1INH-nf First, then Placebo
1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks.
Biological: C1 esterase inhibitor [human] (C1INH-nf) Drug: Placebo (saline)
Experimental: Placebo First, then C1INH-nf
Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks.
Biological: C1 esterase inhibitor [human] (C1INH-nf) Drug: Placebo (saline)

Detailed Description:

Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).

The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).

A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed 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
  • Relatively frequent angioedema attacks (at least 2 per month on average)

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: NCT01005888

Locations
United States, Arizona
Allergy and Immunology Associates
Scottsdale, Arizona, United States, 85251
United States, California
University of California, San Diego
San Diego, California, United States, 92093-0732
Allergy and Asthma Clinical Research, Inc
Walnut Creek, California, United States, 94598
United States, Georgia
Atlanta Allergy and Asthma Clinic
Suwanee, Georgia, United States, 30024
United States, Hawaii
Hawaii Pacific Health Research Institute
Honolulu, Hawaii, United States, 96826
United States, Indiana
Welborn Clinic Allergy and Immunology
Evansville, Indiana, United States, 47713
United States, Louisiana
Lake Charles Memorial Hospital
Lake Charles, Louisiana, United States, 70601
United States, Maryland
Institute for Asthma and Allergy
Wheaton, Maryland, United States, 20902
United States, Montana
Libby Clinic
Libby, Montana, United States, 59923
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Nationwide Childrens Hospital Clinical Research
Columbus, Ohio, United States, 43205
United States, Oklahoma
Allergy Clinic of Tulsa
Tulsa, Oklahoma, United States, 74133
United States, Oregon
Allergy Asthma and Dermatology Research Center
Lake Oswego, Oregon, United States, 97035
United States, Texas
AARA Research Center
Dallas, Texas, United States, 75231
Tyler County Hospital
Woodville, Texas, United States, 75979
United States, West Virginia
St. Joseph's Hospital/Cornerstone Healthcare
Parkersburg, West Virginia, United States, 26101
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: NCT01005888     History of Changes
Other Study ID Numbers: LEVP2005-1/Part B
Study First Received: October 29, 2009
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
Cardiovascular Diseases
Genetic Diseases, Inborn
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Vascular
Urticaria
Vascular Diseases
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1s
Complement Inactivating Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014