hereditary angioedema MedDRA version: 20.0 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: C1 esterase inhibitor liquid for injection
Product Code: SHP616
Pharmaceutical Form: Solution for injection
INN or Proposed INN: C1 Esterase Inhibitor (human)
Other descriptive name: COM
Sponsors
Shire ViroPharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be =12 years of age, or in Germany and Israel, be =18 years of age. 2. Have a diagnosis of HAE (Type I or II) and a functional C1 INH level less than 50% of normal. 3. Meet one of the following criteria (attack rate may be based on subject recall in conjunction with the subject’s medical records): a. If subject is adult (>18 years of age) and currently receiving prophylactic therapy with C1 INH, have a history of =2.0 angioedema attacks per month (average) during the 3 consecutive months prior to starting prevention therapy. OR b. If subject is adolescent (>12 and 18 years of age) and currently receiving a stable dose of attenuated androgens, have a history of =2.0 angioedema attacks per month (average) during the 3 consecutive months prior to the screening visit. 4. For subjects =18 years of age, be willing to receive treatment with icatibant for any angioedema attacks that occur during the study that, in the opinion of the healthcare care provider, require medical intervention. Note: For subjects =12 to =65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Adults (>18 years of age) receiving prophylactic IV CINRYZE that exceeds the approved dosing regimen of 1000 U every 3 or 4 days (receiving a weekly dose >2000 U). 2. Adolescents (>12 and <18 years of age) currently receiving prophylactic therapy with C1 INH (not applicable to Germany and Israel). 3. Have had signs or symptoms of an angioedema attack within 2 days prior to the first dose of investigational product in Treatment Period 1. 4. Have received any C1 INH therapy or any blood product for the treatment or prevention of angioedema attacks within 3 calendar days prior to the first dose of investigational product in Treatment Period 1. 5. If female, have started or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (ie, estrogen/progestin containing products) within 2 months prior to the screening visit. 6. Have a history of hypercoagulability (abnormal blood clotting) or other predisposition for thromboembolism. 7. Have a diagnosis of acquired angioedema or known presence of anti-C1 INH antibodies. 8. Have a history of allergic reaction to C1 INH products, including CINRYZE (or any components of CINRYZE), or other blood products, or FIRAZYR (icatibant). 9. Be pregnant or breastfeeding. 10. Have received an investigational drug within 30 days prior to the first dose of investigational product in Treatment Period 1. 11. Have, as determined by the investigator and/or the sponsor’s medical monitor, any surgical or medical condition (including positive for hepatitis B, hepatitis C, or HIV infection; alcohol, drug, or medication abuse within 1 year before screening; or mental condition rendering the subject or parent(s)/legal guardian unable to understand the nature, scope of the study, and possible consequences of the study), or relationship to study staff or sponsor (including people accommodated in an institution as well as people who are dependent on the sponsor, CRO, site or the investigator) that could interfere with the administration of investigational product or interpretation of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate superior efficacy of SC administration of 2000 IU C1 esterase inhibitor [human] liquid for injection for the prevention of angioedema attacks relative to placebo based on the normalized number of attacks (NNA) during a treatment period.;Secondary Objective: The key secondary objective is to demonstrate the superior efficacy of SC administration of 2000 IU C1 esterase inhibitor [human] liquid for injection for the prevention of angioedema attacks relative to placebo as measured by the proportion of subjects meeting the criterion of at least 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period: 1. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period. 2. The NNA during each treatment period excluding the first 2 weeks. 3. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA for the 2000IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period excluding the first 2 weeks of each treatment period.;Primary end point(s): The normalized number of attacks (NNA) recorded during each treatment period. The NNA is computed as the number of attacks per month (ie, 30.4 days) of exposure (NNA = 30.4 x [number of attacks during treatment period]/[days of treatment period]). If a subject discontinues during the treatment period, the denominator of the NNA will be the days on treatment for that subject; this is equivalent to the last observation carried forward imputation method to impute the missing information following the subject’s discontinuation;Timepoint(s) of evaluation of this end point: 14 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoints: 1. The proportion of subjects meeting the criterion of at least a 50% reduction in the NNA during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period. 2. The NNA excluding the first 2 weeks of each treatment period 3. The proportion of subjects meeting the criterion of at least 50% reduction in the NNA for the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period excluding the first 2 weeks of each treatment period. Key secondary endpoints 1 and 3 are defined as achieving a = 50% reduction in the NNA (PR) during the 2000 IU C1 esterase inhibitor [human] liquid for injection treatment period relative to the placebo period. The Key secondary endpoints 1 and 3 will be analyzed as the proportion of subjects meeting criterion PR. The null hypothesis is that PR is less than or equal to 0.2 and the alternative hypothesis is that PR is greater than 0.2. The proportion meeting criterion PR will be estimated with an exact 95% CI. The lower limit of the 95% CI for the proportion will be compared with 0.2. Analysis of key secondary endpoint 2 will follow the same method (ie, the linear mixed effect model) used for the primary efficacy endpoint.;Timepoint(s) of evaluation of this end point: 14 weeks | — |
Countries
Canada, Germany, Hungary, Israel, Romania, Spain, United States
Contacts
Public ContactHoward Mayer
Shire ViroPharma, Inc.
Outcome results
None listed