C1-Esteraseremmer-N for the Treatment of Hereditary (and Acquired) Angioedema - Full Text View

Sponsored by:	Sanquin
Information provided by:	Sanquin
ClinicalTrials.gov Identifier:	NCT00125151

Purpose

A multicentre study to investigate the pharmacokinetics, clinical efficacy and safety of nanofiltered Cetor® (called C1-esteraseremmer-N during the development phase) for the treatment of hereditary angioedema (HAE) will be performed. This study (KB2003.01) consists of three parts: Part A - pharmacokinetics (phase II); Part B - treatment of attacks of angioedema (phase III); and Part C - prophylactic use of C1 inhibitor (phase III). Parts B + C will provide data on the efficacy of C1-esteraseremmer-N.

The changes within the manufacturing process of C1-esteraseremmer-N, compared to Cetor® nanofiltration and omission of hepatitis B immunoglobulin, most likely will not affect tolerability. The nanofiltration will provide more safety regarding viruses.

In Part B of the study, 15 attacks of hereditary angioedema will be treated with open-label C1-esteraseremmer-N. Attack severity and duration will be monitored by the subjective experience of the patient himself (which has been shown to be the most sensitive way of monitoring attack severity) and compared with historical (and literature) data. If possible, some attacks of acquired angioedema will also be included.

Condition	Intervention	Phase
Angioedema	Drug: C1 inhibitor concentrate (C1-esteraseremmer-N)	Phase III

Drug Information available for: C1 esterase inhibitor

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Pharmacokinetics, Clinical Efficacy and Safety of C1 Inhibitor Concentrate (C1-Esteraseremmer-N) for the Treatment of Hereditary (and Acquired) Angioedema

Further study details as provided by Sanquin:

Primary Outcome Measures:

The primary objective in this clinical study, in which patients use C1-esteraseremmer-N to treat an attack of angioedema, is to investigate the efficacy and the time-to-effect of C1-esteraseremmer-N.

Secondary Outcome Measures:

Secondary objectives are the safety of C1-esteraseremmer-N and the ability of C1-esteraseremmer-N to increase the C1 inhibitor level and activity.

Estimated Enrollment:

15

Detailed Description:

A multicentre study to investigate the pharmacokinetics, clinical efficacy and safety of nanofiltered Cetor® (called C1-esteraseremmer-N during the development phase) for the treatment of hereditary angioedema (HAE) will be performed. This study (KB2003.01) consists of three parts: Part A - pharmacokinetics (phase II); Part B - treatment of attacks of angioedema (phase III); and Part C - prophylactic use of C1 inhibitor (phase III). Parts B + C will provide data on the efficacy of C1-esteraseremmer-N.

The changes within the manufacturing process of C1-esteraseremmer-N, compared to Cetor® nanofiltration and omission of hepatitis B immunoglobulin, most likely will not affect tolerability. The nanofiltration will provide more safety regarding viruses.

In Part B of the study, 15 attacks of hereditary angioedema will be treated with open-label C1-esteraseremmer-N. Attack severity and duration will be monitored by the subjective experience of the patient himself (which has been shown to be the most sensitive way of monitoring attack severity) and compared with historical (and literature) data. If possible, some attacks of acquired angioedema will also be included.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Inclusion criteria for HAE type I and type II patients:

Established diagnosis of hereditary angioedema (type I or II): markedly decreased C1 inhibitor activity; decreased (type I), normal or elevated (type II) level of C1 inhibitor antigen; decreased level of C4.
Age ≥ 16 years
Evidence of a peripheral, abdominal, facial, laryngeal or genitourinary attack of angioedema of moderate to severe intensity, starting less then 5 hours before infusion. An attack is defined as moderate if it affects the normal daily activities of the patient in any way. Severe attacks are defined by the inability to perform normal daily activities.
Signed informed consent by patient and patient’s legal representative if under 18 years old

Inclusion criteria for acquired angioedema patients:

Established diagnosis of acquired angioedema: recurrent attacks of angioedema without urticaria; no family history; decreased functional C1 inhibitor; decreased level of C4.
Autoantibodies to C1 inhibitor or decreased C1q or onset after the third decade of life.
Age ≥ 16 years
Evidence of a peripheral, abdominal, facial, laryngeal or genitourinary attack of angioedema of moderate to severe intensity, starting less then 5 hours before infusion. An attack is defined as moderate if it affects the normal daily activities of the patient in any way. Severe attacks are defined by the inability to perform normal daily activities.
Currently treated with C1 inhibitor concentrate to reverse angioedema.
Signed informed consent by patient and patient’s legal representative if under 18 years old

Exclusion Criteria:

Exclusion criteria for HAE type I and type II patients:

Presence of clinically-relevant anti-C1 inhibitor auto-antibodies
Participation in another pharmaceutical clinical study, which can interfere with this study, in the last 3 months prior to the study, other than Part A of this protocol.
Addiction to narcotic/pain medication in case of an abdominal attack
B-cell malignancy
Use of narcotic medication within 3 days prior to attack.
Use of heparin within the last two days prior to the study
Pregnancy or lactation
History of allergic reactions to C1 inhibitor concentrate or other blood products

Exclusion criteria for acquired angioedema patients:

Participation in another pharmaceutical clinical study, which can interfere with this study, in the last 3 months prior to the study
Addiction to narcotic/pain medication in case of an abdominal attack
Use of narcotic medication within 3 days prior to attack.
Use of heparin within the last two days prior to the study
Pregnancy or lactation.
History of allergic reactions to C1 inhibitor concentrate or other blood products

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00125151

Contacts

Contact: M. M. Levi, Prof. Dr.

+31-20-5662171

Locations

Netherlands
Academic Medical Centre
Amsterdam, Netherlands, 1100 DD
Erasmus Medical Centre
Rotterdam, Netherlands, 3015 GD
Academic hospital Groningen
Groningen, Netherlands, 9700 RB

Sponsors and Collaborators

Sanquin

Investigators

Principal Investigator:

M. M. Levi, Prof. Dr.

Academic Medical Centre Amsterdam

More Information

Study ID Numbers:	KB2003.01B
Study First Received:	July 28, 2005
Last Updated:	February 26, 2007
ClinicalTrials.gov Identifier:	NCT00125151
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Sanquin:

MeSH: angioneurotic edema, complement 1 inactivators
Hereditary angioedema type I or II, Acquired angioedema

Study placed in the following topic categories:

Hypersensitivity
Skin Diseases
Angioedema
Hypersensitivity, Immediate
Vascular Diseases

Edema
Urticaria
Angioedema, Hereditary
Hereditary angioedema
Complement C1 Inhibitor Protein

Additional relevant MeSH terms:

Skin Diseases, Vascular
Immune System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009