Hereditary AngioedemaPhase 3PASSIONNCT00748202
Berinert P Study of Subcutaneous Versus Intravenous Administration
A Phase 3 study testing C1-Esterase Inhibitor in people with Hereditary Angioedema, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- C1-Esterase Inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2008to Dec 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital
Frankfurt am Main, Hesse, 60590
About this study
Official title: Pharmacokinetics Berinert P Study of Subcutaneous Versus Intravenous Administration in Subjects With Moderate Hereditary Angioedema - The Passion Study
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.
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- C1-Esterase Inhibitor
- Keywords
- Hereditary angioedema, C1-Esterase inhibitor, intravenous, subcutaneous, pharmacokinetic
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-Esterase InhibitorDrug
Also called Berinert P
1000 I.E.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | 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 Receives: Drug: C1-Esterase Inhibitor |
| 2 | Active comparator | 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. Receives: Drug: C1-Esterase Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Individual courses of C1-inhibitor levels, from these will be derived pharmacokinetic parameters
Measured: 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.
Secondary outcomes (1)
Safety of s.c. and i.v. administration of study medication
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johann Wolfgang Goethe University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical trial center Rhine-Main, ZKI Kindergerinnungslabor, Institut für Medizinische Virologie JWG-University hospital, CSL Behring, PharmaPart, University of Milan
- Investigators
- Wolfhart Kreuz, PD Phd, Principal investigator, Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00748202
- Sponsor's protocol ID
- CE1145_1001
- Acronym
- PASSION
- Status last verified
- Jan 2011
- First submitted
- 4 Sep 2008
- Last updated
- 19 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Martinez-Saguer I, Cicardi M, Suffritti C, Rusicke E, Aygoren-Pursun E, Stoll H, Rossmanith T, Feussner A, Kalina U, Kreuz W. Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study. Transfusion. 2014 Jun;54(6):1552-61. doi: 10.1111/trf.12501. Epub 2013 Nov 24.
PubMed 24266596
Study at a glance
From the registry record, last updated by the sponsor on 19 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics Berinert P Study of Subcutaneous Versus Intravenous Administration in Subjects With Moderate Hereditary Angioedema - The Passion Study
- ClinicalTrials.gov ID
- NCT00748202
- Acronym / sponsor ID
- PASSION / CE1145_1001
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary angioedema, C1-Esterase inhibitor, intravenous, subcutaneous, pharmacokinetic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Johann Wolfgang Goethe University HospitalUniversity, hospital or other
- Collaborators
- Clinical trial center Rhine-Main, ZKI Kindergerinnungslabor, Institut für Medizinische Virologie JWG-University hospital, CSL Behring, PharmaPart, University of Milan
- Study start
- Sep 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 8 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: C1-Esterase Inhibitorintravenous 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 |
| 2 | Active comparator | Drug: C1-Esterase Inhibitorsubcutaneous 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C1-Esterase InhibitorAlso: Berinert P1000 I.E. | Drug | 1, 2 |
Primary outcome
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.
1 secondary outcome
Safety of s.c. and i.v. administration of study medication
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jan 2011.
- Derived from this study: PubMed 24266596Martinez-Saguer I, Cicardi M, Suffritti C, Rusicke E, Aygoren-Pursun E, Stoll H, Rossmanith T, Feussner A, Kalina U, Kreuz W. Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study. Transfusion. 2014 Jun;54(6):1552-61. doi: 10.1111/trf.12501. Epub 2013 Nov 24.
Related trials for Hereditary Angioedema
RecruitingPhase 3
Donidalorsen Treatment in Children With Hereditary Angioedema
Hereditary Angioedema (HAE)
RecruitingObservational study
A Study of Takhzyro in Teenagers and Adults With Hereditary Angioedema (HAE) in South Korea
Hereditary Angioedema (HAE)
Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wolfhart Kreuz, PD Phd principal investigator
Centre of Paediatrics III, Department of Haematology, Haemostaseology and Oncology, Comprehensive Care Centre for Thrombosis and Haemostasis, Johann-Wolfgang-Goethe-University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing C1-Esterase Inhibitor in people with Hereditary Angioedema, run by Johann Wolfgang Goethe University Hospital at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00748202, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2011.