Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

Phase 3

Completed

• Conditions: Hereditary Angioedema
• Interventions: Drug: Placebo (Saline); Drug: rhC1INH

• Registration Number: NCT01188564
• Lead Sponsor: Pharming Technologies B.V.

Brief Summary

This study is being conducted to confirm the efficacy, safety, and immunogenicity of recombinant human C1 inhibitor (rhC1INH) at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in Hereditary Angioedema (HAE) patients.

Detailed Description

HAE is characterized by recurrent localized angioedema caused by uncontrolled activation of the complement and contact systems due to a congenital deficiency of functional C1 inhibitor.

rhC1INH has been developed to offer a more widely available therapeutic alternative to the existing plasma-derived C1INH (pdC1INH) products that have been used in the treatment of acute angioedema attacks patients with HAE.

Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack will be evaluated for eligibility. 75 eligible patients will be randomized (3:2) to receive an intravenous infusion of rhC1INH or saline in a double-blind fashion. Open-label rhC1INH may be provided as rescue medication to patients who do not experience the beginning of relief within 4 hours or who experience life-threatening oropharyngeal-laryngeal angioedema symptoms.

Any patient having received a randomized treatment will be allowed to receive treatment with rhC1INH in an open-label fashion for subsequent eligible attacks.

Study Timeline

• Study First Submitted: 2010-08-24
• Study First Submitted QC: 2010-08-24
• Study First Posted: 2010-08-25
• Study Start: 2011-01
• Primary Completion: 2012-12
• Study Completion: 2013-03
• Disposition First Submitted: 2013-07-02
• Disposition First Submitted QC: 2013-07-02
• Disposition First Posted: 2013-07-09
• Results First Submitted: 2015-06-10
• Status Verified: 2015-07
• Results First Submitted QC: 2015-08-03
• Last Update Submitted: 2015-08-03
• Results First Posted: 2015-08-07
• Last Update Posted: 2015-08-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Aged at least 13 years
• Signed written informed consent
• Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal
• Willingness and ability to comply with all protocol procedures
• Clinical symptoms of an eligible HAE attack with onset less than 5 hours before the time of initial evaluation

Exclusion Criteria

• Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit dander IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent).
• A diagnosis of acquired C1INH deficiency (AAE)
• Pregnancy, or breastfeeding, or current intention to become pregnant
• Treatment with any investigational drug in the past 30 days
• Known or suspected addiction to drug and/or alcohol abuse
• Suspicion for an alternate explanation of the symptoms other than acute HAE attack

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (Saline)	Placebo (Saline)	-
rhC1INH	rhC1INH	-

Primary Outcome Measures

Name	Time	Method
Time to Beginning of Relief of Symptoms	Patients observed for 24 hours	Time to beginning of relief is the time lapsed from the beginning of the infusion of study medication to the beginning of a beneficial effect based on patient's responses to the Treatmetn Effect Questionnaire (TEQ) for the primary attack location. The beginning of relief is defined as the first timepoint at which; * The patient reports any of the following answers for TEQ question 1: "A little better", "Better" or "Much better"; and; * The patient reports the following answer for TEQ question 2: "Yes"; and,; * There is persistence in improvement at the next assessment time, i.e.either the same or a better response to Question 1 and "Yes" to Question 2.

Secondary Outcome Measures

Name	Time	Method
Time to Minimal Symptoms	24 hours	The key secondary efficacy endpoint was the time to minimal symptoms at all locations. The time to achieving minimal symptoms was defined as an answer of "Yes" to TEQ question 3.

Trial Locations

Locations (27)

Allergy, Asthma & Immunology, Assoc, Ltd.; 🇺🇸 Scottsdale, Arizona, United States

Allergy and Asthma Institute of the Valley; 🇺🇸 Granada Hills, California, United States

UCLA Department of Medicine Division of Clinical Immunology, David Geffen School of Medicine; 🇺🇸 Los Angeles, California, United States

USF Asthma, Allergy and Immunology Clinical Research Unit; 🇺🇸 Tampa, Florida, United States

Family Allergy and Asthma Center; 🇺🇸 Atlanta, Georgia, United States

Institute for Asthma and Allergy, P.C.; 🇺🇸 Chevy Chase, Maryland, United States

Asthma & Allergy Center - Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

University of Cincinnati Physicians, Inc.; 🇺🇸 Cincinnati, Ohio, United States

Optimed Research, LTD; 🇺🇸 Columbus, Ohio, United States

Baker Allergy, Asthma and Dermatology Research Center, LLC; 🇺🇸 Lake Oswego, Oregon, United States

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