A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT00914966
First received: June 3, 2009
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

The objectives of the study were:

  1. To assess the safety and tolerability of escalating doses of CINRYZE.
  2. To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
  3. To assess the immunogenicity of CINRYZE.

Condition Intervention Phase
Hereditary Angioedema
Biological: C1 inhibitor (human) [C1 INH]
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance [ Time Frame: 12 to 24 weeks at each dose level ] [ Designated as safety issue: Yes ]
    Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.


Secondary Outcome Measures:
  • Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates [ Time Frame: 12 weeks at each dose level ] [ Designated as safety issue: No ]

    Two definitions of success were applied in this study:

    1. Per-protocol success - Average angioedema attack rate of ≤1.0 per month at the end of any dose escalation step (Week 12). The a priori definition of study success was 4 or more subjects with per-protocol success.
    2. Investigator-determined success - Based on the investigator's clinical judgment, an average monthly angioedema attack rate demonstrating improvement sufficient for progression to follow-up.

    In addition, subjects who were not a per-protocol or investigator-determined success, but who experienced a reduction of >1.0 attack per month from their historical angioedema attack rate at the end of any dose escalation step (Week 12), were summarized.


  • Use of Rescue Therapy and/or Other Therapy for Treatment of HAE Symptoms [ Time Frame: 12 weeks at each dose level ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: July 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CINRYZE

There were 3 potential dose escalation steps:

  • Step 1: 1500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
  • Step 2: 2000 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
  • Step 3: 2500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
Biological: C1 inhibitor (human) [C1 INH]
Other Names:
  • CINRYZE
  • C1 esterase inhibitor (human)

Detailed Description:

Qualifying subjects entered a 3-step dose escalation algorithm:

  • Step 1: 1500 Units twice per week (starting dosing regimen for all subjects in the study)
  • Step 2: 2000 Units twice per week
  • Step 3: 2500 Units twice per week

Each step consisted of 12 weeks of safety monitoring, followed by calculation of average monthly angioedema attack rate based on subject reports of angioedema symptoms (regardless of intensity) and actual duration of therapy for that step.

If a subject was deemed a "success" at a given step and the investigator and medical monitor determined that it was safe for the subject to continue on that dose, the subject entered a 3 month follow-up period at that dose level with continued safety monitoring. The subject could not re-enter the study for purposes of dose escalation during the follow-up period.

If a subject was not deemed a "success," the subject initiated the next highest step of the dose escalation algorithm provided that the investigator and medical monitor agreed that dose escalation was appropriate. If at the end of Step 3 (2500 Units), a subject was not deemed a "success," then the Week 12 visit represented study completion and the subject was referred to the physician who manages their HAE care.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

To be eligible for this protocol, subjects must:

  1. Be ≥6 years of age and ≥25 kg body weight.
  2. Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:

    • C1 INH gene mutation
    • C4 level below the lower limit of the reference range
    • C1 INH antigen level below the lower limit of the reference range
    • Functional C1 INH level below the lower limit of the reference range
    • Family history of HAE (i.e., grandparent, parent, sibling)
  3. Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
  4. If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.

    OR

  5. If a child, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).

Exclusion Criteria:

To be eligible for this protocol, subjects must not:

  1. 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.
  2. Have a history of abnormal blood clotting or other coagulopathy.
  3. Be taking prescription anticoagulant medication.
  4. Have a history of allergic reaction to CINRYZE or other blood products.
  5. Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
  6. Have received any blood products (other than CINRYZE) within 60 days prior to screening.
  7. Have any of the following laboratory values at screening:

    • Hemoglobin <8 g/dL
    • White blood cell count <2 x 10^9/L or >20 x 10^9/L
    • Platelet count <50 x 10^9/L or >400 x 10^9/L
    • Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.0 x the upper limit of normal
    • Blood urea nitrogen and/or creatinine >2.0 x the upper limit of normal
  8. Be pregnant or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00914966

Locations
United States, Arizona
Allergy, Asthma and Immunology Associates
Scottsdale, Arizona, United States, 85251
United States, Georgia
Family Allergy and Asthma Center
Atlanta, Georgia, United States, 30342
United States, Maryland
Institute for Asthma and Allergy
Wheaton, Maryland, United States, 20902
United States, New York
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, Ohio
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
United States, Oregon
Allergy and Asthma Research Group
Eugene, Oregon, United States, 97401
Baker Allergy, Asthma and Dermatology Research Center
Lake Oswego, Oregon, United States, 97035
United States, Tennessee
East Tennessee Center for Clinical Research
Knoxville, Tennessee, United States, 37909
United States, Texas
Bryan, Texas, United States, 77802
AARA Research Center
Dallas, Texas, United States, 75231
United States, Washington
Marycliff Allergy Specialist
Spokane, Washington, United States, 99204
Sponsors and Collaborators
Shire
Investigators
Study Director: Jennifer Schranz, MD, FRCP(C) ViroPharma
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00914966     History of Changes
Other Study ID Numbers: 0624-400
Study First Received: June 3, 2009
Results First Received: May 23, 2013
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014