A Study of the Safety and Efficacy of Subcutaneous Administration of Cinryze with Recombinant Human Hyaluronidase for the Prevention of HAE Attacks

• Conditions: Angioedema.; MedDRA version: 17.1Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Body processes [G] - Genetic Phenomena [G05]

• Registration Number: EUCTR2012-000083-24-SE
• Lead Sponsor: Shire ViroPharma Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05-22
• Last Update Posted: 23 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 47

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 <3 months, but at least 1 month, the subject should satisfy this attack rate (i.e., =1.0 moderate or severe attack per month [average]) for the timeframe that the subject has actually received prophylactic therapy.
AND
• during the 3 consecutive months prior to starting prophylactic therapy, a history of at least 2.0 moderate or severe angioedema attacks per month (average).
NOTE: the attack rate may be estimated based on subject recall.
4. If not on prophylactic C1 INH therapy, have a history of at least 2.0 moderate or severe angioedema attacks per month (average) during the 3 consecutive months prior to randomization.
NOTE: the attack rate may be estimated based on subject recall.
5. Agree to avoid his/her known HAE triggers during the study to the best of his/her ability.
6. Agree to adhere to the protocol-defined schedule of assessments and procedures.
7. If female, be post-menopausal (cessation of menses greater than or equal to 1 year), surgically sterile, or following an acceptable non-hormonal method of birth control such as intrauterine device or barrier control for at least 1 complete menstrual cycle before the screening visit and agree to continue
use through the 30-day post-treatment visit, or using hormonal birth control products for at least 3 months prior to the first dose of study drug in Treatment Period 1 and agree to continue use through the 30-day post-treatment visit.
8. If male, be surgically sterile or agree to follow an acceptable method of birth control (e.g., barrier control) from the screening visit through 2 months after the last dose of study drug.
9. If an adult (=18 years of age), be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
OR
If a child (<18 years of age), have a parent(s)/legal guardian who is informed of the nature of the study provide written informed consent for the child to participate in the study before any study-specific procedures are performed (with assent from the child when appropriate). Alternatively, certain sites/IRAs may permit adolescents who are <18 years of age to be informed of the nature of the study and provide written informed consent without consent from a parent(s)/legal guardian.

To be eligibile for the post treatment follow-up, subjects must:
1. Be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
2. Have anti-rHuPH20 binding antibody titers detected post-baseline at a titer > 1:20.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified