Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks

Hereditary Angioedema (HAE) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01756157
• Other study ID #: 0624-206
• Secondary ID: 2012-000083-24
• Status: Completed
• Phase: Phase 2
• Start date: February 4, 2013
• Est. completion date: September 13, 2013

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: September 13, 2013
• Est. primary completion date: September 13, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema (HAE)

Intervention

Biological:
• CINRYZE with rHuPH20

Locations

Country	Name	City	State
Germany	ViroPharma Investigational Site	Berlin
Germany	ViroPharma Investigational Site	Essen
Germany	ViroPharma Investigational Site	Mainz
Germany	ViroPharma Investigational Site	Munchen
Spain	ViroPharma Investigational Site	Barcelona
Sweden	ViroPharma Investigational Site	Jonkoping
United States	ViroPharma Investigational Site	Bentonville	Arkansas
United States	ViroPharma Investigational Site	Birmingham	Alabama
United States	ViroPharma Investigational Site	Boston	Massachusetts
United States	ViroPharma Investigational Site	Cincinnati	Ohio
United States	ViroPharma Investigational Site	Colorado Springs	Colorado
United States	ViroPharma Investigational Site	Columbus	Ohio
United States	ViroPharma Investigational Site	Dallas	Texas
United States	ViroPharma Investigational Site	Hershey	Pennsylvania
United States	ViroPharma Investigational Site	Knoxville	Tennessee
United States	ViroPharma Investigational Site	Lake Oswego	Oregon
United States	ViroPharma Investigational Site	Las Vegas	Nevada
United States	ViroPharma Investigational Site	Mineola	New York
United States	ViroPharma Investigational Site	Pittsburgh	Pennsylvania
United States	ViroPharma Investigational Site	Scottsdale	Arizona
United States	ViroPharma Investigational Site	Spokane	Washington
United States	ViroPharma Investigational Site	Tampa	Florida
United States	ViroPharma Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Germany,  Spain,  Sweden, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary	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.	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary	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.	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary	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.	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary	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.	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period