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

A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks of Angioedema in Patients With HAE

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Drug: rhC1INH; Drug: Placebo (Saline)

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 Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1527
    • UMHAT "Tsaritsa Yoanna - ISUL"; Clinic of Ear-Nose-Throat Diseases
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, KIY 4G2
      • Ottawa Allergy Research Corp.
• Hungary
  • Budapest, Hungary, H-1125
    • Semmelweis University Faculty of Medicine, III Department of Internal Medicine
• Israel
  • Haifa, Israel, 31048
    • Bnei-Zion Medical Centre, Clinical Immunology and Allergy Division
  • Ramat Gan
    • Tel Hashomer, Ramat Gan, Israel, 52621
      • Allergy, Immunology & Angioedema Center,
• Italy
  • Milan, Italy, 20157
    • Ospedale Luigi Sacco, Azienda Ospedaliera - Polo Universitario II Divisione di Medicina Interna
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • P.H.U. Clinic for Dermatology, Medical University Skopje, Unit of Allergology and Clinical Immunology
• Poland
  • Krakow, Poland, 31-531
    • Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Klinik Chorób Wewnętrznych, Poradnia Alergologiczna
• Romania
  • Târgu-Mureş, Romania, 540103
    • Spitalul Clinic Judeţean Mureş Secţia Clinică Medicină Internă, Compartimentul de Alergologie şi Imunologie
• Serbia
  • Belgrade, Serbia, 11000
    • Clinic for Immunology and Allergology
• South Africa
  • Mowbray, South Africa, 7700
    • Allergy Diagnostic & Clinical Research Unit University of Cape Town Lung Institute
  • Parktown, South Africa, 2193
    • Wits Health Consortium (Pty) Ltd - Wits Donald Gordon Medical Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Allergy, Asthma & Immunology, Assoc, Ltd.
  • California
    • Granada Hills, California, United States, 91344
      • Allergy and Asthma Institute of the Valley
    • Los Angeles, California, United States, 90095
      • UCLA Department of Medicine Division of Clinical Immunology, David Geffen School of Medicine
  • Florida
    • Tampa, Florida, United States, 33613
      • USF Asthma, Allergy and Immunology Clinical Research Unit
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Family Allergy and Asthma Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma and Allergy, P.C.
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Asthma & Allergy Center - Washington University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Physicians, Inc.
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Baker Allergy, Asthma and Dermatology Research Center, LLC
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State- Milton S. Hershey Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center
    • Galveston, Texas, United States, 77555
      • University of Texas - Medical Branch
    • Irving, Texas, United States, 75063
      • Allergy, Asthma & Immunology Clinic, P.A.
  • Washington
    • Spokane, Washington, United States, 99204
      • Marycliff Allergy Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhC1INH	Drug: rhC1INH; One i.v. injection of rhC1INH at the dose of 50 U/kg, for patients up to 84 kg; one i.v. injection of rhC1INH at the dose of 4200U (2 vials) for patients of 84 kg body weight or greater.
Placebo Comparator: Placebo (Saline)	Drug: Placebo (Saline); One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Beginning of Relief of Symptoms	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.	Patients observed for 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Minimal Symptoms	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.	24 hours

Collaborators and Investigators

• Sponsor: Pharming Technologies B.V.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: August 24, 2010
• First Submitted That Met QC Criteria: August 24, 2010
• First Posted (Estimate): August 25, 2010

Study Record Updates

• Last Update Posted (Estimate): August 7, 2015
• Last Update Submitted That Met QC Criteria: August 3, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: HAE; Hereditary Angioedema; Angioedema; Recombinant C1 Inhibitor; rhC1INH
• 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
• Other Study ID Numbers: C1 1310