Clinical Trial: Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:
Sponsor: Shire

Current Primary Outcome: Normalized Number of Angioedema Attacks During the Treatment Period [ Time Frame: 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.


Original Primary Outcome: Number of angioedema attacks during each randomized therapy period [ Time Frame: 8 weeks ]

Current Secondary Outcome:

  • Cumulative Attack-severity During the Treatment Period [ Time Frame: 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 Daily-severity During the Treatment Period [ Time Frame: 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 Symptomatic Days During the Treatment Period [ Time Frame: 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 [ Time Frame: 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.


Original Secondary Outcome: Cumulative Attack-Severity during each randomized therapy period [ Time Frame: 8 weeks ]

This score is the sum of the maximum symptom severity recorded for each angioedema attack in a treatment period.


Information By: Shire

Dates:
Date Received: June 29, 2012
Date Started: December 2012
Date Completion:
Last Updated: May 29, 2015
Last Verified: June 2014