A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CINRYZE Administration

An Open-Label Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous (SC) Versus Intravenous (IV) Administration of CINRYZE in Adolescents and Adults With Hereditary Angioedema (HAE)

The objectives of the study are to:

1. Evaluate the safety and tolerability of CINRYZE administered by subcutaneous injection in subjects with hereditary angioedema
2. Characterize the pharmacokinetics and pharmacodynamics of CINRYZE administered by subcutaneous injection
3. Assess the immunogenicity of CINRYZE following subcutaneous administration

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Biological: CINRYZE

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy, Asthma and Immunology Associates
  • California
    • Walnut Creek, California, United States, 94598
      • Allergy and Asthma Clinical Research, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy and Asthma Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma and Allergy
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Allergy, Asthma and Dermatology Research Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
  • Washington
    • Spokane, Washington, United States, 99204
      • Marycliff Allergy Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

To be eligible for this protocol, a subject must:

1. Have a confirmed diagnosis of HAE.
2. During the 3 consecutive months prior to screening, have a history of less than 1 HAE attack per month (average) treated with C1INH therapy or any other blood products, ecallantide (Kalbitor), icatibant (Firazyr), antifibrinolytics (e.g., tranexamic acid), IV fluids, or narcotic analgesics.
3. Agree to strictly adhere to the protocol-defined schedule of assessments and procedures.

Exclusion Criteria:

To be eligible for this protocol, a subject must not:

1. Have received C1INH therapy or any blood products for treatment or prevention of an HAE attack within 14 days prior to the first dose.
2. Have received any ecallantide (Kalbitor), icatibant (Firazyr), or antifibrinolytics (e.g., tranexamic acid) within 14 days prior to the first dose.
3. Have any change (start, stop, or change in dose) in androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 14 days prior to the first dose.
4. 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.
5. Have a history of abnormal blood clotting or other coagulopathy.
6. Have a history of allergic reaction to CINRYZE or other blood products.
7. Be pregnant or breastfeeding.
8. Have received an immunization within 30 days prior to the first dose.
9. Have participated in any other investigational drug study within 30 days prior to the first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV CINRYZE First, Then SC CINRYZE Dose 1	Biological: CINRYZE; C1 esterase inhibitor (human)
Experimental: IV CINRYZE First, Then SC CINRYZE Dose 2	Biological: CINRYZE; C1 esterase inhibitor (human)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and Severity of Adverse Events, Number of Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study.	18 days in each treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change C1 Inhibitor (C1INH)	Mean Change in Baseline in Observed Plasma Concentration of C1 Inhibitor (C1INH) Antigen. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.	18 days in each treatment period
Mean Change C4 Compliment	Mean Change in Baseline in Observed Plasma Concentration of C4 Compliment. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.	18 days in each treatment period
Number of Participants With C1 Inhibitor (INH) Antibodies		18 days in each treatment period

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2010
• Primary Completion (Actual): December 16, 2010
• Study Completion (Actual): December 16, 2010

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: March 26, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Subcutaneous; HAE; C1 inhibitor (C1INH)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: 0624-200; SPD616-200 (Other Identifier: Sponsor)