Postmarketing Immunogenicity Study in HAE Subjects Treated With Berinert

Prospective Open-label Uncontrolled Multi-center Post-marketing Study to Assess Inhibitory Antibody Formation in Subjects With Congenital C1-INH Deficiency and Acute Hereditary Angioedema (HAE) Attacks Treated With Berinert® , a C1-esterase Inhibitor

This is a prospective, international, multi-center, non-randomized, single arm, open-label, postmarketing study to investigate the formation of inhibitory anti-C1-INH antibodies in HAE subjects treated intravenously with Berinert. Individual treatment duration per subject is 9 months, irrespective of the number of treated attacks. All subjects will receive 20 IU Berinert/kg body weight per attack.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema Types I and II
• Intervention / Treatment: Biological: Berinert, lyophilizate for IV application containing 500 IU C1-INH to be reconstituted with 10 mL water for injection

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1504
    • MHAT "Tsaritsa Yoanna"
• Hungary
  • Budapest, Hungary, 1125
    • Semmelweis University
• Poland
  • Krakow, Poland, 31-531
    • Jagiellonian University
• Romania
  • Mureş
    • Târgu-Mures, Mureş, Romania, Cod 540103
      • Spitalul Clinic Judeţean Mureş,Secţia Clinică Medicină Internă,Compartimentul Alergologie şi Imunologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of congenital C1-INH deficiency (HAE type I or II) and assessed by the investigator to likely require intravenous (IV) Berinert treatment during the study period.
• Male or female, ≥ 12 years of age at the time of signing informed consent.
• Written informed consent for study participation obtained before undergoing any study specific procedures.

Exclusion Criteria:

• Incurable malignancies in the last 6 months prior to study entry.
• Acquired angioedema due to C1-INH deficiency.
• All other types of angioedema not associated with C1-INH deficiency.
• Use of any C1-INH products other than Berinert within 30 days before the study, or planned use during the study.
• Immunization within 30 days prior to study entry.
• Autoimmune conditions requiring use of immunosuppressants during the study.
• Known or suspected hypersensitivity to C1-INH.
• Participation in any of the previous Berinert studies from which anti-C1-INH antibody results were submitted to the Food and Drug Administration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Berinert	Biological: Berinert, lyophilizate for IV application containing 500 IU C1-INH to be reconstituted with 10 mL water for injection; Individual treatment duration per subject is 9 months, irrespective of the number of treated attacks. Each attack that occurs in this time frame will be treated with 20 IU Berinert/kg body weight.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Inhibitory Anti-C1-esterase-inhibitor Antibodies	Subjects with no positive baseline result and at least one positive post-baseline result for inhibitory anti-C1-INH antibodies.	Baseline to approximately 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies	Subjects with at least one positive result for inhibitory or non-inhibitory anti-C1-INH antibodies.	Baseline to approximately 9 months

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Mikhail Rojavin, CSL Behring

Publications and helpful links

General Publications

• Farkas H, Varga L, Moldovan D, Obtulowicz K, Shirov T, Machnig T, Feuersenger H, Edelman J, Williams-Herman D, Rojavin M. Assessment of inhibitory antibodies in patients with hereditary angioedema treated with plasma-derived C1 inhibitor. Ann Allergy Asthma Immunol. 2016 Nov;117(5):508-513. doi: 10.1016/j.anai.2016.08.025. Epub 2016 Oct 24.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: November 7, 2011
• First Submitted That Met QC Criteria: November 8, 2011
• First Posted (ESTIMATE): November 9, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 6, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• 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; Hereditary Angioedema Types I and II; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins
• Other Study ID Numbers: CE1145_4001; 2010-024242-30 (EUDRACT_NUMBER)