Clinical trial NCT00914966: A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hereditary Angioedema
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-06-05
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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 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.

Primary outcomes:
measure: 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
timeFrame: 12 to 24 weeks at each dose level
Secondary outcomes:
measure: Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
timeFrame: 12 weeks at each dose level
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Allergy, Asthma and Immunology Associates
state: Arizona
city: Atlanta
country: United States
facility: Family Allergy and Asthma Center
state: Georgia
city: Wheaton
country: United States
facility: Institute for Asthma and Allergy
state: Maryland
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Eugene
country: United States
facility: Allergy and Asthma Research Group
state: Oregon
city: Lake Oswego
country: United States
facility: Baker Allergy, Asthma and Dermatology Research Center
state: Oregon
city: Knoxville
country: United States
facility: East Tennessee Center for Clinical Research
state: Tennessee
city: Bryan
country: United States
state: Texas
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Spokane
country: United States
facility: Marycliff Allergy Specialist
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: