E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
congenital C1-INH deficiency and acute hereditary angioedema (HAE) attacks |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019860 |
E.1.2 | Term | Hereditary angioedema |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To document the formation of inhibitory anti-C1-esterase-inhibitor (anti-C1-INH) antibodies in subjects with HAE treated with Berinert.
The study will evaluate the hypothesis that the incidence of inhibitory anti-C1-INH antibodies in subjects with HAE treated with Berinert is less than 20% of the total study population. |
|
E.2.2 | Secondary objectives of the trial |
To document the safety of Berinert in subjects with HAE treated with Berinert.
Exploratory Objective:
To document the efficacy of Berinert in subjects with HAE treated with Berinert for all types of HAE attacks, and to compare efficacy in subjects with and without anti-C1-INH antibodies. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Diagnosis of congenital C1-INH deficiency (HAE type I or II) and assessed by the investigator to likely require 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. |
|
E.4 | Principal exclusion criteria |
Incurable malignancies in the last 6 months prior to study entry.
Acquired angioedema (AAE) due to C1-INH deficiency (eg, onset at >40 years of age, no family history of congenital C1-INH deficiency, low C1q plasma level, and no known HAE mutation).
All other types of angioedema not associated with C1-INH deficiency (eg, including anaphylactic angioedema).
Participation in another clinical study.
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.
Alcohol, drug, or medication abuse within 1 year before the study.
Suspected inability (eg, language problems) or unwillingness to comply with study procedures.
Known or suspected hypersensitivity to C1-INH.
Any condition that is likely to interfere with evaluation of the investigational medicinal product (IMP) or satisfactory conduct of the study.
Employee at the study center, or spouse/partner or relative of anyone of the study staff.
Participation in any of the previous Berinert studies from which anti-C1-INH antibody results were submitted to the Food and Drug Administration.
Female subjects of childbearing potential either not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study, or for whom sexual abstinence for the entire duration of the study is not conceivable.
Pregnant women (pregnancy test required), or intention to become pregnant during the course of the study, women currently breast-feeding, or with the intention to breast feed.
Re-entry of subjects participating in the current study who had previously been withdrawn for any reason. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of inhibitory anti-C1-INH antibodies. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of subjects with any anti-C1-INH antibodies (inhibitory or non-inhibitory).
Adverse events.
Laboratory safety parameters.
Vital signs.
Time to onset of symptom relief.
Time to complete resolution of HAE symptoms. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
assessment of inhibitory antibody formation |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The day of the last visit of the last subject enrolled in the study |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |