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

Hereditary Angioedema Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01188564
• Other study ID #: C1 1310
• Status: Completed
• Phase: Phase 3
• First received: August 24, 2010
• Last updated: August 3, 2015
• Start date: January 2011
• Est. completion date: March 2013

Study information

• Verified date: July 2015
• Source: Pharming Technologies B.V.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

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 (Saline)
One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment

Locations

Country	Name	City	State
Bulgaria	UMHAT "Tsaritsa Yoanna - ISUL"; Clinic of Ear-Nose-Throat Diseases	Sofia
Canada	Ottawa Allergy Research Corp.	Ottawa	Ontario
Hungary	Semmelweis University Faculty of Medicine, III Department of Internal Medicine	Budapest
Israel	Bnei-Zion Medical Centre, Clinical Immunology and Allergy Division	Haifa
Israel	Allergy, Immunology & Angioedema Center,	Tel Hashomer	Ramat Gan
Italy	Ospedale Luigi Sacco, Azienda Ospedaliera - Polo Universitario II Divisione di Medicina Interna	Milan
Macedonia, The Former Yugoslav R	P.H.U. Clinic for Dermatology, Medical University Skopje, Unit of Allergology and Clinical Immunology	Skopje
Poland	Szpital Uniwersytecki w Krakowie, Oddzial Kliniczny Klinik Chorób Wewnetrznych, Poradnia Alergologiczna	Krakow
Romania	Spitalul Clinic Judetean Mures Sectia Clinica Medicina Interna, Compartimentul de Alergologie si Imunologie	Târgu-Mures
Serbia	Clinic for Immunology and Allergology	Belgrade
South Africa	Allergy Diagnostic & Clinical Research Unit University of Cape Town Lung Institute	Mowbray
South Africa	Wits Health Consortium (Pty) Ltd - Wits Donald Gordon Medical Centre	Parktown
United States	Family Allergy and Asthma Center	Atlanta	Georgia
United States	Institute for Asthma and Allergy, P.C.	Chevy Chase	Maryland
United States	University of Cincinnati Physicians, Inc.	Cincinnati	Ohio
United States	Optimed Research, LTD	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	University of Texas - Medical Branch	Galveston	Texas
United States	Allergy and Asthma Institute of the Valley	Granada Hills	California
United States	Pennsylvania State- Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Allergy, Asthma & Immunology Clinic, P.A.	Irving	Texas
United States	Baker Allergy, Asthma and Dermatology Research Center, LLC	Lake Oswego	Oregon
United States	UCLA Department of Medicine Division of Clinical Immunology, David Geffen School of Medicine	Los Angeles	California
United States	Allergy, Asthma & Immunology, Assoc, Ltd.	Scottsdale	Arizona
United States	Marycliff Allergy Specialists	Spokane	Washington
United States	Asthma & Allergy Center - Washington University School of Medicine	St. Louis	Missouri
United States	USF Asthma, Allergy and Immunology Clinical Research Unit	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pharming Technologies B.V.

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Hungary,  Israel,  Italy,  Macedonia, The Former Yugoslav Republic of,  Poland,  Romania,  Serbia,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No