A multicentre study to investigate 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). Part B + C will provide data on the efficacy of C1-esteraseremmer-N.

The changes within in 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 the most sensitive way of monitoring attack severity, and compared with historical (and literature) data. If possible, also some attacks of acquired angioedema will be included.

Condition	Intervention	Phase
Hereditary angioedema type I or II, Acquired angioedema	Drug: C1 inhibitor concentrate	Phase III

Further Study Details: 

Primary Outcomes: 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, the time-to-effect, of C1-esteraseremmer-N.
Secondary Outcomes: Secondary objectives are the safety of C1-esteraseremmer-N and the ability of C1-esteraseremmer-N to increase the C1 inhibitor level and activity.
Expected Total Enrollment:  15

A multicentre study to investigate 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). Part B + C will provide data on the efficacy of C1-esteraseremmer-N.

The changes within in 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 the most sensitive way of monitoring attack severity, and compared with historical (and literature) data. If possible, also some attacks of acquired angioedema will be included.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria: Inclusion criteria for HAE type I and 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 moderate if it affects normal daily activities of the patient in any way. Severe attacks are defined by the inability to perform normal daily activities.  Signed informed consent of 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 moderate if it affects 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 of patient and patient’s legal representative if under 18 years old

Exclusion Criteria: Exclusion criteria for HAE type I and II patients:  Presence of clinical-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.  Usage 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.  Usage of heparin within the last two days prior to the study  Pregnancy or lactation.  History of allergic reaction to C1 inhibitor concentrate or other blood products

Please refer to this study by ClinicalTrials.gov identifier  NCT00125151

M. M. Levi, Prof. Dr.      +31-20-5662171 

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

Study chairs or principal investigators

M. M. Levi, Prof. Dr.,  Principal Investigator,  Academic Medical Centre Amsterdam   

Study ID Numbers:  KB2003.01B
Last Updated:  August 1, 2005
Record first received:  July 29, 2005
ClinicalTrials.gov Identifier:  NCT00125151
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
ClinicalTrials.gov processed this record on 2005-08-02