Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks

Phase 2

Completed

Conditions: Hereditary Angioedema (HAE)

Interventions: Biological: CINRYZE with rHuPH20

Registration Number: NCT01756157

Lead Sponsor: Shire

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1	CINRYZE with rHuPH20	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.
SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2	CINRYZE with rHuPH20	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.

Primary Outcome Measures

Name	Time	Method
Normalized Number of Angioedema Attacks During the Treatment Period	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each 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

Name	Time	Method
Cumulative Daily-severity During the Treatment Period	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each 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 Attack-severity During the Treatment Period	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each 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 Symptomatic Days During the Treatment Period	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each 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	From Visit 1 (Week 1) up to Visit 16 (Week 8) during each 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.