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

Primary Purpose

Hereditary Angioedema

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
C1 esterase inhibitor [human] (C1INH-nf)
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema focused on measuring Hereditary angioedema, C1 esterase inhibitor (human)

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Allergy and Immunology Associates
  • Allergy and Asthma Clinic of Northwest Arkansas
  • UCLA-David Geffen School of Medicine
  • University of California, San Diego
  • Allergy and Asthma Clinical Research, Inc
  • Allergy and Asthma Center
  • Orlando Regional Healthcare
  • Family Allergy and Asthma Center
  • Welborn Clinic Allergy and Immunology
  • Institute for Asthma and Allergy
  • University of Massachusetts Medical School
  • Grand Traverse Allergy
  • MeritCare Clinical Research
  • Nevada Access to Research and Education Society
  • UMDNJ Asthma and Allergy Research Center
  • Montefiore Medical Center
  • Winthrop University Hospital
  • Mount Sinai School of Medicine
  • MeritCare Clinical Research
  • Allergy & Asthma Centre of Dayton
  • Allergy Clinic of Tulsa
  • Allergy Asthma and Dermatology Research Center
  • Penn State University
  • Allergy Partners of the Upstate
  • AARA Research Center
  • University of Texas Medical Branch
  • Baylor College of Medicine
  • Allergy and Asthma Research Center
  • Marycliff Allergy Specialists
  • Cornerstone Healthcare

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-label C1INH-nf

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
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.

Secondary Outcome Measures

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.
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.
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.
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).
Complement C4 Serum Levels
Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.

Full Information

First Posted
February 21, 2007
Last Updated
May 19, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00438815
Brief Title
Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks
Acronym
CHANGE 2
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 21, 2006 (Actual)
Primary Completion Date
March 31, 2009 (Actual)
Study Completion Date
March 31, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
Keywords
Hereditary angioedema, C1 esterase inhibitor (human)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-label C1INH-nf
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
C1 esterase inhibitor [human] (C1INH-nf)
Primary Outcome Measure Information:
Title
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
Time Frame
Duration of the study (2.5 years)
Title
Percent of HAE Attacks With Substantial Relief of the Defining Symptom
Description
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.
Time Frame
Within 4 hours after initial treatment
Secondary Outcome Measure Information:
Title
Time to Beginning of Substantial Relief of the Defining Symptom
Description
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 Frame
Within 4 hours after initial treatment
Title
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
Description
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.
Time Frame
Within 4 hours after initial treatment
Title
Antigenic C1 Inhibitor (C1INH) Serum Levels
Description
Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Time Frame
Pre-infusion to 1 hour post-infusion
Title
Functional C1INH Serum Levels
Description
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).
Time Frame
Pre-infusion to 1 hour post-infusion
Title
Complement C4 Serum Levels
Description
Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Time Frame
Pre-infusion to 1 hour post-infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Allergy and Immunology Associates
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
Allergy and Asthma Clinic of Northwest Arkansas
City
Bentonville
State/Province
Arkansas
ZIP/Postal Code
72712
Country
United States
Facility Name
UCLA-David Geffen School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093-0732
Country
United States
Facility Name
Allergy and Asthma Clinical Research, Inc
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Allergy and Asthma Center
City
Fort Lauderdale
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
Facility Name
Orlando Regional Healthcare
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Family Allergy and Asthma Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Welborn Clinic Allergy and Immunology
City
Evansville
State/Province
Indiana
ZIP/Postal Code
47713
Country
United States
Facility Name
Institute for Asthma and Allergy
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Grand Traverse Allergy
City
Traverse City
State/Province
Michigan
ZIP/Postal Code
49684
Country
United States
Facility Name
MeritCare Clinical Research
City
Bemidji
State/Province
Minnesota
ZIP/Postal Code
56601
Country
United States
Facility Name
Nevada Access to Research and Education Society
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
UMDNJ Asthma and Allergy Research Center
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Winthrop University Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
MeritCare Clinical Research
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58122
Country
United States
Facility Name
Allergy & Asthma Centre of Dayton
City
Centerville
State/Province
Ohio
ZIP/Postal Code
45458
Country
United States
Facility Name
Allergy Clinic of Tulsa
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74133
Country
United States
Facility Name
Allergy Asthma and Dermatology Research Center
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
Penn State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Allergy Partners of the Upstate
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-1083
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Allergy and Asthma Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Marycliff Allergy Specialists
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Cornerstone Healthcare
City
Parkersburg
State/Province
West Virginia
ZIP/Postal Code
26101
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23484892
Citation
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.
Results Reference
derived
PubMed Identifier
23312695
Citation
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.
Results Reference
derived
PubMed Identifier
22856635
Citation
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.
Results Reference
derived
PubMed Identifier
22192966
Citation
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.
Results Reference
derived
PubMed Identifier
20818886
Citation
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.
Results Reference
derived

Learn more about this trial

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

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