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

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ClinicalTrials.gov Identifier: NCT00438815
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : June 9, 2010
Last Update Posted : April 15, 2014
Sponsor:
Information provided by:
Shire

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hereditary Angioedema
Intervention Biological: C1 esterase inhibitor [human] (C1INH-nf)
Enrollment 113
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description 1,000 Units (U) of C1 esterase inhibitor (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.
Period Title: Overall Study
Started 113
Completed 43
Not Completed 70
Reason Not Completed
Transferred to LEVP2006-4 (NCT00462709)             30
3-month follow-up no longer required             12
Noncompliance with protocol requirements             9
Transitioned to commercial C1INH-nf             6
Lost to Follow-up             6
Withdrawal by Subject             6
Death             1
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Baseline Participants 113
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 113 participants
34.5  (17.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 113 participants
Female
75
  66.4%
Male
38
  33.6%
1.Primary Outcome
Title Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
Hide Description [Not Specified]
Time Frame Duration of the study (2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat Efficacy (ITT-E) Population (N=101; the number of subjects who received at least one dose of C1INH-nf for the treatment of an acute HAE attack).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 101
Measure Type: Number
Unit of Measure: attacks
Conservative Analysis 609
Less Conservative Analysis 598
2.Primary Outcome
Title Percent of HAE Attacks With Substantial Relief of the Defining Symptom
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population (N=101; the number of subjects who received at least one dose of C1INH-nf for the treatment of an acute HAE attack).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 101
Measure Type: Number
Unit of Measure: percent of attacks
Conservative Analysis 87
Less Conservative Analysis 95
3.Secondary Outcome
Title Time to Beginning of Substantial Relief of the Defining Symptom
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E Population.
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 101
Median (95% Confidence Interval)
Unit of Measure: hours
0.75
(0.50 to 1.00)
4.Secondary Outcome
Title Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E subjects with at least 10 HAE attacks during the study (N=15).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 15
Median (95% Confidence Interval)
Unit of Measure: hours
Attack number 1
1.50
(0.75 to 4.00)
Attack number 2
0.50
(0.25 to 2.50)
Attack number 3
0.50
(0.50 to 0.75)
Attack number 4
0.50
(0.25 to 1.00)
Attack number 5
0.75
(0.50 to 1.25)
Attack number 6
0.50
(0.25 to 1.25)
Attack number 7
0.75
(0.50 to 0.75)
Attack number 8
0.50
(0.25 to 0.75)
Attack number 9
0.25
(0.25 to 0.50)
Attack number 10
0.50
(0.25 to 0.75)
5.Secondary Outcome
Title Antigenic C1 Inhibitor (C1INH) Serum Levels
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E subjects with data at both sampling time points (N=84).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 84
Mean (Standard Deviation)
Unit of Measure: mg/dL
Pre-infusion 10.7  (13.91)
Increase at 1 hour post-infusion 9.6  (12.98)
6.Secondary Outcome
Title Functional C1INH Serum Levels
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E subjects with data at both sampling time points (N=82).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 82
Mean (Standard Deviation)
Unit of Measure: percent of functional C1INH
Pre-infusion 27.0  (19.30)
Percent increase at 1 hour post-infusion 39.2  (18.04)
7.Secondary Outcome
Title Complement C4 Serum Levels
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-E subjects with data at both sampling time points (N=74).
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description:
1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Overall Number of Participants Analyzed 74
Mean (Standard Deviation)
Unit of Measure: mg/dL
Pre-infusion 5.3  (5.41)
Change at 1 hour post-infusion -0.2  (1.51)
Time Frame [Not Specified]
Adverse Event Reporting Description Presented are all treatment-emergent adverse reactions considered to be related to C1INH-nf.
 
Arm/Group Title Open-label C1INH-nf
Hide Arm/Group Description 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
All-Cause Mortality
Open-label C1INH-nf
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Open-label C1INH-nf
Affected / at Risk (%)
Total   0/113 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.5%
Open-label C1INH-nf
Affected / at Risk (%)
Total   1/113 (0.88%) 
General disorders   
Infusion site pain  1/113 (0.88%) 
Skin and subcutaneous tissue disorders   
Rash  1/113 (0.88%) 
1
Term from vocabulary, MedDRA (9.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Clinical Study Agreement. Most restrictive provision - PI will not publish results until after first of: multicenter publication is published or 24 months from study end. Thereafter, PI may publish his results. PI must provide copy of proposed publication to sponsor for pre-review. If sponsor requests, PI must delete sponsor confidential information before publication and/or delay publication for 90 days so sponsor can file for patents or take other action to protect its patent rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Scientific Officer
Organization: ViroPharma
Phone: 610-458-7300
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Chief Scientific Officer, ViroPharma
ClinicalTrials.gov Identifier: NCT00438815     History of Changes
Other Study ID Numbers: LEVP2006-1
First Submitted: February 21, 2007
First Posted: February 22, 2007
Results First Submitted: March 31, 2010
Results First Posted: June 9, 2010
Last Update Posted: April 15, 2014