Back to resultsSubcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks
Primary Purpose
Hereditary Angioedema (HAE)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CINRYZE with rHuPH20
Sponsored by
About this trial
This is an interventional prevention trial for Hereditary Angioedema (HAE) focused on measuring Crossover, C1 esterase inhibitor, Prevention, C1 inhibitor, Hereditary Angioedema, Subcutaneous, Recombinant human hyaluronidase
Eligibility Criteria
Inclusion Criteria:
- Be ≥12 years of age.
- Have a confirmed diagnosis of Hereditary Angioedema.
Exclusion Criteria:
- Receipt of any C1 inhibitor (C1 INH) therapy or any blood products for treatment or prevention of an angioedema attack within 7 days before the first dose of study drug.
- Be receiving prophylactic intravenous CINRYZE that exceeds 1000 units every 3 or 4 days (maximum weekly dose 2000 units).
- Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug.
- 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.
- History of allergic reaction to C1 INH products, including CINRYZE or other blood products.
- History of abnormal blood clotting.
- Have a known allergy to hyaluronidase or any other ingredient in the study formulation.
Sites / Locations
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
- ViroPharma Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2
SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1
Arm Description
SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks.
SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks.
Outcomes
Primary Outcome Measures
Normalized Number of Angioedema Attacks During the Treatment Period
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Secondary Outcome Measures
Cumulative Attack-severity During the Treatment Period
Cumulative Attack-severity score was the sum of maximum symptom severity recorded for each angioedema attack, determined on the last day of symptoms and recorded as None=0, Mild=1, Moderate=2, and Severe=3 and summing over the unique attacks, yields a Cumulative Attack-severity score. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative attack-severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Cumulative Daily-severity During the Treatment Period
Cumulative Daily-severity score was the sum of the severity scores recorded for every day of reported symptoms during the treatment period. Severity scores were recorded as None=0, Mild=1, Moderate=2, and Severe=3. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative daily severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Cumulative Symptomatic Days During the Treatment Period
Cumulative symptomatic days was defined as the sum of the symptomatic days of each angioedema attack reported during the treatment period. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. Cumulative symptomatic days was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Number of Angioedema Attacks Requiring Acute Treatment During the Treatment Period
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01756157
Brief Title
Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks
Official Title
A Phase 2, Randomized, Double-Blind, Multicenter, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase (rHuPH20) for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
February 4, 2013 (Actual)
Primary Completion Date
September 13, 2013 (Actual)
Study Completion Date
September 13, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of two doses of CINRYZE with recombinant human hyaluronidase (rHuPH20) administered by subcutaneous (SC) injection to prevent angioedema attacks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema (HAE)
Keywords
Crossover, C1 esterase inhibitor, Prevention, C1 inhibitor, Hereditary Angioedema, Subcutaneous, Recombinant human hyaluronidase
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2
Arm Type
Experimental
Arm Description
SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks.
Arm Title
SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1
Arm Type
Experimental
Arm Description
SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks.
Intervention Type
Biological
Intervention Name(s)
CINRYZE with rHuPH20
Other Intervention Name(s)
C1 esterase inhibitor (human), Recombinant human hyaluronidase
Primary Outcome Measure Information:
Title
Normalized Number of Angioedema Attacks During the Treatment Period
Description
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Time Frame
From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary Outcome Measure Information:
Title
Cumulative Attack-severity During the Treatment Period
Description
Cumulative Attack-severity score was the sum of maximum symptom severity recorded for each angioedema attack, determined on the last day of symptoms and recorded as None=0, Mild=1, Moderate=2, and Severe=3 and summing over the unique attacks, yields a Cumulative Attack-severity score. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative attack-severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Time Frame
From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Title
Cumulative Daily-severity During the Treatment Period
Description
Cumulative Daily-severity score was the sum of the severity scores recorded for every day of reported symptoms during the treatment period. Severity scores were recorded as None=0, Mild=1, Moderate=2, and Severe=3. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative daily severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Time Frame
From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Title
Cumulative Symptomatic Days During the Treatment Period
Description
Cumulative symptomatic days was defined as the sum of the symptomatic days of each angioedema attack reported during the treatment period. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. Cumulative symptomatic days was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Time Frame
From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Title
Number of Angioedema Attacks Requiring Acute Treatment During the Treatment Period
Description
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Time Frame
From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be ≥12 years of age.
Have a confirmed diagnosis of Hereditary Angioedema.
Exclusion Criteria:
Receipt of any C1 inhibitor (C1 INH) therapy or any blood products for treatment or prevention of an angioedema attack within 7 days before the first dose of study drug.
Be receiving prophylactic intravenous CINRYZE that exceeds 1000 units every 3 or 4 days (maximum weekly dose 2000 units).
Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug.
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.
History of allergic reaction to C1 INH products, including CINRYZE or other blood products.
History of abnormal blood clotting.
Have a known allergy to hyaluronidase or any other ingredient in the study formulation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
ViroPharma Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
ViroPharma Investigational Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85251
Country
United States
Facility Name
ViroPharma Investigational Site
City
Bentonville
State/Province
Arkansas
ZIP/Postal Code
72712
Country
United States
Facility Name
ViroPharma Investigational Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
ViroPharma Investigational Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
ViroPharma Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
ViroPharma Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
ViroPharma Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
ViroPharma Investigational Site
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
ViroPharma Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
ViroPharma Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
ViroPharma Investigational Site
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
ViroPharma Investigational Site
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
ViroPharma Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15241
Country
United States
Facility Name
ViroPharma Investigational Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
ViroPharma Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
ViroPharma Investigational Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
ViroPharma Investigational Site
City
Berlin
Country
Germany
Facility Name
ViroPharma Investigational Site
City
Essen
Country
Germany
Facility Name
ViroPharma Investigational Site
City
Mainz
Country
Germany
Facility Name
ViroPharma Investigational Site
City
Munchen
Country
Germany
Facility Name
ViroPharma Investigational Site
City
Barcelona
Country
Spain
Facility Name
ViroPharma Investigational Site
City
Jonkoping
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
27931305
Citation
Riedl MA, Lumry WR, Li HH, Banerji A, Bernstein JA, Ba M, Bjrkander J, Magerl M, Maurer M, Rockich K, Chen H, Schranz J. Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema. Allergy Asthma Proc. 2016 Nov;37(6):489-500. doi: 10.2500/aap.2016.37.4006.
Results Reference
result
PubMed Identifier
36326435
Citation
Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
Results Reference
derived
Learn more about this trial
Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks
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