Hereditary Angioedema
Conditions
Keywords
Hereditary angioedema, C1 esterase inhibitor (human)
Brief summary
The study objective was to evaluate the safety and efficacy of prophylactic use of C1INH-nf for the prevention of acute HAE attacks.
Interventions
BIOLOGICALC1 esterase inhibitor [human] (C1INH-nf)
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- History of at least 1 HAE attack per month or any history of laryngeal edema In addition, this study was open to all subjects who: * Completed participation in LEVP2005-1/B (NCT01005888) any time after the final prophylactic therapy in Part B * Were enrolled but not randomized in LEVP2005-1/A (NCT00289211) after Part A was closed * Were enrolled and randomized in LEVP2005-1/A after LEVP2005-1/B was closed to enrollment, any time after the 3-day telephone follow-up * Were excluded from LEVP2005-1 for any of the following reasons: * Pregnancy or lactation * Age less than 6 years * Narcotic addiction * Presence of anti-C1 inhibitor (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 other than those sponsored by Lev Pharmaceuticals * Received blood or a blood product in the past 60 days other than C1INH-nf
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of All HAE Attacks | Duration of the study | A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Antigenic C1 Inhibitor (C1INH) Serum Levels | Pre-infusion to 1 hour post-infusion | Change from pre-infusion to 1 hour post-infusion in antigenic C1INH serum levels. |
| Functional C1INH Serum Levels | Pre-infusion to 1 hour post-infusion | Change from pre-infusion to 1 hour post-infusion in functional C1INH serum levels. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH). |
| Complement C4 Serum Levels | Pre-infusion to 1 hour post-infusion | Change from pre-infusion to 1 hour post-infusion in complement C4 serum levels. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label C1INH-nf 1,000 U of C1INH-nf administered IV every 3 to 7 days. | 146 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Logistical reasons | 2 |
| Overall Study | Lost to Follow-up | 10 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Transferred to LEVP2006-1 (NCT00438815) | 3 |
| Overall Study | Transitioned to commercial C1INH-nf | 40 |
| Overall Study | Withdrawal by Subject | 8 |
| Overall Study | Withdrew to start treatment with Cetor | 1 |
Baseline characteristics
| Characteristic | Open-label C1INH-nf |
|---|---|
| Age, Continuous | 36.5 years STANDARD_DEVIATION 16.48 |
| Sex: Female, Male Female | 112 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 146 |
| serious Total, serious adverse events | 0 / 146 |
Outcome results
Primary
Frequency of All HAE Attacks
A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema.
Time frame: Duration of the study
Population: Intent-to-treat Efficacy (ITT-E) Population (N=146; the number of subjects who received at least one prophylactic dose of C1INH-nf for the prevention of HAE attacks). HAE attack frequency was reported by 137 subjects at screening (i.e., data were missing for 9 subjects).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Open-label C1INH-nf | Frequency of All HAE Attacks | At Screening (N=137) | 3.00 attacks per month |
| Open-label C1INH-nf | Frequency of All HAE Attacks | During Prophylactic Therapy with C1INH-nf (N=146) | 0.21 attacks per month |
Other Pre-specified
Antigenic C1 Inhibitor (C1INH) Serum Levels
Change from pre-infusion to 1 hour post-infusion in antigenic C1INH serum levels.
Time frame: Pre-infusion to 1 hour post-infusion
Population: ITT-E subjects with data at both sampling time points (N=137).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label C1INH-nf | Antigenic C1 Inhibitor (C1INH) Serum Levels | Pre-infusion | 17.1 mg/dL | Standard Deviation 19.67 |
| Open-label C1INH-nf | Antigenic C1 Inhibitor (C1INH) Serum Levels | Increase at 1 hour post-infusion | 8.6 mg/dL | Standard Deviation 11.89 |
Other Pre-specified
Complement C4 Serum Levels
Change from pre-infusion to 1 hour post-infusion in complement C4 serum levels.
Time frame: Pre-infusion to 1 hour post-infusion
Population: ITT-E subjects with data at both sampling time points (N=134).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label C1INH-nf | Complement C4 Serum Levels | Pre-infusion | 10.1 mg/dL | Standard Deviation 8.17 |
| Open-label C1INH-nf | Complement C4 Serum Levels | Change at 1 hour post-infusion | -0.1 mg/dL | Standard Deviation 3.61 |
Other Pre-specified
Functional C1INH Serum Levels
Change from pre-infusion to 1 hour post-infusion in functional C1INH serum levels. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH).
Time frame: Pre-infusion to 1 hour post-infusion
Population: ITT-E subjects with data at both sampling time points (N=132).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open-label C1INH-nf | Functional C1INH Serum Levels | Pre-infusion | 42.0 percent | Standard Deviation 25.85 |
| Open-label C1INH-nf | Functional C1INH Serum Levels | Percent increase at 1 hour post-infusion | 30.4 percent | Standard Deviation 18.05 |