Angioedema. MedDRA version: 14.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: CINRYZE
Pharmaceutical Form: Powder and solvent for solution for injection
Other descriptive name: COMPLEMENT C1 ESTERASE INHIBITOR
Concentration unit: U unit(s)
Concentration type: equal
Sponsors
ViroPharma Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be =12 years of age. 2. Have a confirmed diagnosis of HAE with a history of at least one of the following: • C1 INH antigen level below normal • Functional C1 INH level below normal 3. If currently receiving prophylactic IV CINRYZE therapy (i.e., 1000 U every 3 or 4 days or up to 2000 U per week) or other C1 INH therapy, have: • during the 3 consecutive months prior to randomization, an angioedema attack rate of =1.0 moderate or severe attack per month (average). NOTE: if the duration of prophylactic therapy is =65 years) yes F.1.3.1 Number of subjects for this age range 2 ;Inclusion criteria: 1. Be =12 years of age. 2. Have a confirmed diagnosis of HAE with a history of at least one of the following: • C1 INH antigen level below normal • Functional C1 INH level below normal 3. If currently receiving prophylactic IV CINRYZE therapy (i.e., 1000 U every 3 or 4 days or up to 2000 U per week) or other C1 INH therapy, have: • during the 3 consecutive months prior to randomization, an angioedema attack rate of =1.0 moderate or severe attack per month (average). NOTE: if the duration of prophylactic therapy is =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Have received any C1 INH therapy or any blood products for treatment or prevention of an angioedema attack within 7 days prior to the first dose of study drug in Treatment Period 1. 2. Be receiving prophylactic IV CINRYZE that exceeds the approved dosing regimen of 1000 U every 3 or 4 days (maximum weekly dose of 2000 U). 3. Have had angioedema attack signs or symptoms within 2 days prior to the first dose of study drug in Treatment Period 1. 4. Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug in Treatment Period 1. 5. If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug in Treatment Period 1. 6. Have a history of hypercoagulability (abnormal blood clotting). 7. Have a diagnosis of acquired angioedema or known to have 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. 9. Have a known allergy to hyaluronidase or any other ingredient in the study formulation. 10. Be pregnant or breastfeeding. 11. Have received an investigational study drug within 30 days prior to the first dose of study drug in Treatment Period 1. 12. Have, as determined by the Investigator and/or the Sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results. ;Exclusion criteria: 1. Have received any C1 INH therapy or any blood products for treatment or prevention of an angioedema attack within 7 days prior to the first dose of study drug in Treatment Period 1. 2. Be receiving prophylactic IV CINRYZE that exceeds the approved dosing regimen of 1000 U every 3 or 4 days (maximum weekly dose of 2000 U). 3. Have had angioedema attack signs or symptoms within 2 days prior to the first dose of study drug in Treatment Period 1. 4. Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug in Treatment Period 1. 5. If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug in Treatment Period 1. 6. Have a history of hypercoagulability (abnormal blood clotting). 7. Have a diagnosis of acquired angioedema or known to have 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. 9. Have a known allergy to hyaluronidase or any other ingredient in the study formulation. 10. Be pregnant or breastfeeding. 11. Have received an investigational study drug within 30 days prior to the first dose of study drug in Treatment Period 1. 12. Have, as determined by the Investigator and/or the Sponsor's medical monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 1000 U and 2000 U doses of CINRYZE with rHuPH20 administered by SC injection to prevent angiodema attacks. To assess the safety and tolerability of CINRYZE with rHuPH20 administered by SC injection.;Secondary Objective: To determine the optimal dose of CINRYZE with rHuPH20 administered by SC injection for prevention of angioedema attacks based upon benefit-risk assessment. To further characterize the PK/PD of CINRYZE with rHuPH20 administered by SC injection. To assess the immunogenicity of CINRYZE with rHuPH20 following SC administration. To assess subject acceptance of SC administration of CINRYZE with rHuPH20 for prevention of angioedema attacks. To evaluate subject experience with self administration of SC CINRYZE with rHuPH20. To assess health status (quality of life) of this patient population.;Primary end point(s): The primary efficacy endpoint is the number of angioedema attacks recorded during each treatment period, normalized for the number of days the subject participated in that period.;Timepoint(s) of evaluation of this end point: End of the treatment period.;Main Objective: To evaluate the efficacy of 1000 U and 2000 U doses of CINRYZE with rHuPH20 administered by SC injection to prevent angiodema attacks. To assess the safety and tolerability of CINRYZE with rHuPH20 administered by SC injection.;Secondary Objective: To determine the optimal dose of CINRYZE with rHuPH20 administered by SC injection for prevention of angioedema attacks based upon benefit-risk assessment. To further characterize the PK/PD of CINRYZE with rHuPH20 administered by SC injection. To assess the immunogenicity of CINRYZE with rHuPH20 following SC administration. To assess subject acceptance of SC administration of CINRYZE with rHuPH20 for prevention of angioedema attacks. To evaluate subject experience with self administration of SC CINRYZE with rHuPH20. To assess health status (quality of life) of this patient population.;Primary end | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Cumulative Attack-Severity. This score is the sum of the maximum symptom severity recorded for each angioedema attack in a treatment period. • Cumulative Daily-Severity. This score is the sum of the severity scores recorded for every day of reported symptoms in a treatment period. • Time (measured in days from the first dose of study drug in a treatment period) to the first angioedema attack reported in that treatment period. • Effects of C1 INH and C4 levels on clinical outcome (frequency, severity or anatomic location of attack) during each treatment period. • Number of angioedema attacks requiring acute treatment during each treatment period.;Timepoint(s) of evaluation of this end point: End of the treatment period.;Secondary end point(s): •Cumulative Attack-Severity. This score is the sum of the maximum symptom severity recorded for each angioedema attack in a treatment period. • Cumulative Daily-Severity. This score is the sum of the severity scores recorded for every day of reported symptoms in a treatment period. • Time (measured in days from the first dose of study drug in a treatment period) to the first angioedema attack reported in that treatment period. • Effects of C1 INH and C4 levels on clinical outcome (frequency, severity or anatomic location of attack) during each treatment period. • Number of angioedema attacks requiring acute treatment during each treatment period.;Timepoint(s) of evaluation of this end point: End of the treatment period. | — |
Countries
Germany, Hungary, Spain, Sweden
Contacts
Public ContactDanielle Tierens;Danielle Tierens ;
Viropharma SPRL;Viropharma SPRL
Outcome results
None listed