Berinert P Study of Subcutaneous Versus Intravenous Administration (PASSION)

This study has been completed.
Sponsor:
Collaborators:
Clinical trial center Rhine-Main
ZKI Kindergerinnungslabor
Institut für Medizinische Virologie JWG-University hospital
CSL Behring
Pharmapart GmbH Wiesbaden
University of Milan
Information provided by:
Johann Wolfgang Goethe University Hospitals
ClinicalTrials.gov Identifier:
NCT00748202
First received: September 4, 2008
Last updated: January 18, 2011
Last verified: January 2011
  Purpose

The study is performed to investigate the subcutaneous (s.c.) versus intravenous (i.v.) administration of Berinert P in patients with hereditary angioedema (HAE) to establish a second administration mode in cases where i.v. access is not suitable.

The study is planned as a single centre, randomized, open-label, cross-over pharmacokinetic study.

Subjects will either start with s.c. or i.v. pasteurised C1-Inhibitor concentrate (Berinert P) and than switch to the treatment not administered before.


Condition Intervention Phase
Hereditary Angioedema
Drug: C1-Esterase Inhibitor
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Pharmacokinetics Berinert P Study of Subcutaneous Versus Intravenous Administration in Subjects With Moderate Hereditary Angioedema - The Passion Study

Resource links provided by NLM:


Further study details as provided by Johann Wolfgang Goethe University Hospitals:

Primary Outcome Measures:
  • Individual courses of C1-inhibitor levels, from these will be derived pharmacokinetic parameters [ Time Frame: i.v. and s.c.samples: 0, 0.25, 0.5, 0.75 hours and 1, 2, 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 120, 168, 336 an 504 hours. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of s.c. and i.v. administration of study medication [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: September 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
intravenous administration of C1-Inhibitor, after the end of the first observation period (at least after 7 days), each arm switches cross-over to the alternative administration mode not investigated so far
Drug: C1-Esterase Inhibitor
1000 I.E.
Other Name: Berinert P
Active Comparator: 2
subcutaneous administration of C1-Inhibitor. After the end of the first observation period (at least after 7 days), each arm switches cross-over to the alternative administration mode not investigated so far.
Drug: C1-Esterase Inhibitor
1000 I.E.
Other Name: Berinert P

Detailed Description:

Patients with hereditary angioedema (HAE), suffer from recurring and mostly unforeseeable attacks of acute oedema of subcutaneous tissues of various organs. The pathophysiological correlate of this disease is a deficiency in functionally active C1-Esterase Inhibitor (C1-INH). Today, two main types of HAE are described. In HAE type I, an impaired synthesis and an elevated turnover of a normal and functional active C1-INH molecule takes place, causing reduced amounts in functionally active C1-INH. In HAE type II, normal levels of a functionally impaired C1-INH molecule are synthesized. Both defects are inherited as an autosomal dominant trait. HAE type III is limited to females and not associated with C1-INH deficiency; the pathophysiology of this type remains to be determined. Corticosteroids, antihistamines or epinephrine usually do not exert any positive effect in acute attacks caused by HAE. This is of particular importance as these types of medication are often used in case of oedema in general. In case of acute oedema in patients suffering from HAE, the intravenous administration of C1-INH concentrate (e.g., Berinert P) is the treatment of choice. The study is performed to investigate the s.c. versus i.v. administration of Berinert P in patients with hereditary angioedema (HAE) to establish a second administration mode in cases where i.v. access is not suitable.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with an established diagnosis of HAE type I (C1-Inhibitor activity < 50% and C1-Inhibitor antigen < 15.4 mg/dl) or HAE type II (C1-Inhibitor activity < 50% and C1-Inhibitor antigen in normal or elevated concentration of dysfunctional protein).
  • Male and female subjects with an age of at least 18 years.
  • Subjects providing an informed consent.

Exclusion Criteria:

  • Subjects without an established diagnosis of HAE.
  • Last C1-INH administration less than 7 days ago and/or acute attack.
  • Subjects with acquired angioedema (AAE).
  • All other types of angioedema not associated with C1-INH deficiency.
  • Treatment with any investigational drug (exclusive drugs appropriate for the treatment of acute angioedema) 30 days before study treatment.
  • Treatment with any other drug appropriate for the treatment of acute angioedema within 7 days before start of study treatment at each phase.
  • Danazol prophylaxis.
  • Prophylaxis with antifibrinolytics, EACA, tranexamic acid.
  • Subjects with a known hypersensitivity to study medication (Berinert P).
  • Pregnant women (pregnancy rapid assay required for women with childbearing potential), women currently breast-feeding, or with the intention to breast-feed
  • Subjects with malignant diseases.
  • Subjects with immunodeficiencies such as established acquired immunodeficiency syndrome.
  • Subjects with concurrent serious or acute illness or infection as per investigators judgement.
  • Subjects with mental conditions which render the subject or its legally acceptable representative unable to understand the nature, scope and possible consequences of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748202

Locations
Germany
Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital
Frankfurt, Hessen, Germany, 60590
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospitals
Clinical trial center Rhine-Main
ZKI Kindergerinnungslabor
Institut für Medizinische Virologie JWG-University hospital
CSL Behring
Pharmapart GmbH Wiesbaden
University of Milan
Investigators
Principal Investigator: Wolfhart Kreuz, PD Phd Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital
  More Information

No publications provided by Johann Wolfgang Goethe University Hospitals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: PD Dr. Wolfhart Kreuz, Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis
ClinicalTrials.gov Identifier: NCT00748202     History of Changes
Other Study ID Numbers: CE1145_1001
Study First Received: September 4, 2008
Last Updated: January 18, 2011
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Johann Wolfgang Goethe University Hospitals:
Hereditary angioedema
C1-Esterase inhibitor
intravenous
subcutaneous
pharmacokinetic

Additional relevant MeSH terms:
Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1
Complement C1s
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014