A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
Information source: Shire
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hereditary Angioedema
Intervention: C1 inhibitor (human) [C1 INH] (Biological)
Phase: Phase 4
Status: Completed
Sponsored by: Shire Official(s) and/or principal investigator(s): Jennifer Schranz, MD, FRCP(C), Study Director, Affiliation: ViroPharma
Summary
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.
Clinical Details
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
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: 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
Secondary outcome: Treatment Effect of Escalating Doses of CINRYZE on HAE Attack RatesUse of Rescue Therapy and/or Other Therapy for Treatment of HAE Symptoms
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
Minimum age: 6 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Allergy, Asthma and Immunology Associates, Scottsdale, Arizona 85251, United States
Family Allergy and Asthma Center, Atlanta, Georgia 30342, United States
Institute for Asthma and Allergy, Wheaton, Maryland 20902, United States
Winthrop University Hospital, Mineola, New York 11501, United States
University of Cincinnati Medical Center, Cincinnati, Ohio 45267, United States
Allergy and Asthma Research Group, Eugene, Oregon 97401, United States
Baker Allergy, Asthma and Dermatology Research Center, Lake Oswego, Oregon 97035, United States
East Tennessee Center for Clinical Research, Knoxville, Tennessee 37909, United States
Bryan, Texas 77802, United States
AARA Research Center, Dallas, Texas 75231, United States
Marycliff Allergy Specialist, Spokane, Washington 99204, United States
Additional Information
Starting date: July 2009
Last updated: March 19, 2014
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