Hereditary Angioedema Types I and II
Conditions
Brief summary
This is a prospective, international, multi-center, non-randomized, single arm, open-label, postmarketing study to investigate the formation of inhibitory anti-C1-INH antibodies in HAE subjects treated intravenously with Berinert. Individual treatment duration per subject is 9 months, irrespective of the number of treated attacks. All subjects will receive 20 IU Berinert/kg body weight per attack.
Interventions
BIOLOGICALBerinert, lyophilizate for IV application containing 500 IU C1-INH to be reconstituted with 10 mL water for injection
Individual treatment duration per subject is 9 months, irrespective of the number of treated attacks. Each attack that occurs in this time frame will be treated with 20 IU Berinert/kg body weight.
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of congenital C1-INH deficiency (HAE type I or II) and assessed by the investigator to likely require intravenous (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.
Exclusion criteria
* Incurable malignancies in the last 6 months prior to study entry. * Acquired angioedema due to C1-INH deficiency. * All other types of angioedema not associated with C1-INH deficiency. * 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. * Known or suspected hypersensitivity to C1-INH. * Participation in any of the previous Berinert studies from which anti-C1-INH antibody results were submitted to the Food and Drug Administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Inhibitory Anti-C1-esterase-inhibitor Antibodies | Baseline to approximately 9 months | Subjects with no positive baseline result and at least one positive post-baseline result for inhibitory anti-C1-INH antibodies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Baseline to approximately 9 months | Subjects with at least one positive result for inhibitory or non-inhibitory anti-C1-INH antibodies. |
Countries
Bulgaria, Hungary, Poland, Romania
Participant flow
Pre-assignment details
60 subjects were screened and enrolled in the study. 14 subjects did not experience an HAE attack before the study ended and so did not receive study treatment. 46 subjects started and completed the active treatment period of the study.
Participants by arm
| Arm | Count |
|---|---|
| C1 Esterase Inhibitor Subjects received 20 IU/kg C1 Esterase Inhibitor (C1-INH)/kg body weight by slow intravenous infusion for each acute HAE attack requiring treatment during a 9-month period beginning after their first HAE attack while on study. | 46 |
| Total | 46 |
Baseline characteristics
| Characteristic | C1 Esterase Inhibitor |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age, Continuous | 38.9 years STANDARD_DEVIATION 14.42 |
| Gender Female | 32 Participants |
| Gender Male | 14 Participants |
| Region of Enrollment Bulgaria | 10 participants |
| Region of Enrollment Hungary | 8 participants |
| Region of Enrollment Poland | 13 participants |
| Region of Enrollment Romania | 15 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 46 |
| serious Total, serious adverse events | 2 / 46 |
Outcome results
Primary
Number of Subjects With Inhibitory Anti-C1-esterase-inhibitor Antibodies
Subjects with no positive baseline result and at least one positive post-baseline result for inhibitory anti-C1-INH antibodies.
Time frame: Baseline to approximately 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C1 Esterase Inhibitor | Number of Subjects With Inhibitory Anti-C1-esterase-inhibitor Antibodies | 0 subjects |
Secondary
Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies
Subjects with at least one positive result for inhibitory or non-inhibitory anti-C1-INH antibodies.
Time frame: Baseline to approximately 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C1 Esterase Inhibitor | Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Antibodies detected on Day 1 (Baseline) | 9 Subjects |
| C1 Esterase Inhibitor | Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Antibodies detected post-baseline | 10 Subjects |
| C1 Esterase Inhibitor | Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Antibodies first detected at Month 3 | 2 Subjects |
| C1 Esterase Inhibitor | Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Antibodies first detected at Month 6 | 1 Subjects |
| C1 Esterase Inhibitor | Number of Subjects With Any (Inhibitory or Non-inhibitory) Anti-C1-esterase-inhibitor Antibodies | Antibodies first detected at Month 9 | 1 Subjects |