E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Hereditary angioedema (HAE) is a condition characterized by painful,
recurring attacks of swelling in parts of the body including the face,
throat, hands, feet, abdomen. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to evaluate the efficacy of CSL312 in the
prevention of HAE attacks in subjects with C1-INH HAE. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
1. To further evaluate the efficacy of CSL312 in subjects with C1-INH
HAE
2. To evaluate the pharmacokinetics of CSL312 in subjects with C1-INH
HAE
3. To evaluate the safety and tolerability of CSL312 in subjects with C1-
INH HAE |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female
- Aged ≥ 18 to ≤ 65 years
- A diagnosis of C1-INH HAE or FXII/PLG HAE;
- For subjects with C1-INH HAE: ≥ 4 HAE attacks over a consecutive 2-
month period during the 3 months before Screening, as documented in
the subject's medical record. |
|
E.4 | Principal exclusion criteria |
- History of clinically significant arterial or venous thrombosis, or current
clinically significant prothrombotic risk
- History of an uncontrolled, abnormal bleeding event due to a
coagulopathy, or a current clinically significant coagulopathy or clinically
significant risks for bleeding events
- Known incurable malignancies |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time normalized number of HAE attacks |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. The number of Responder subjects and HAE attack-free subjects with
C1-INH HAE during Treatment Period 1
2. The percentage of Responder subjects and HAE attack-free subjects
with C1-INH HAE during Treatment Period 1
3. The number of mild, moderate or severe HAE attacks, as well as mild,
moderate or severe HAE attacks treated with on-demand HAE
medication, in subjects with C1-INH HAE during Treatment Period 1
4. The time-normalized number of mild, moderate or severe HAE attacks,
as well as mild, moderate or severe HAE attacks treated with on-demand
HAE medication, in subjects with C1-INH HAE during Treatment Period 1
5. The percentage of mild, moderate or severe HAE attacks, as well as
mild, moderate or severe HAE attacks treated with on-demand HAE
medication, in subjects with C1-INH HAE during Treatment Period 1
6. Maximum concentration (Cmax) of CSL312 in subjects with C1-INH
HAE during Treatment Period 1
7. Area under the concentration-time curve in 1 dosing interval (AUC0-
tau) of CSL312 in subjects with C1-INH HAE during Treatment Period 1
8. Time of maximum concentration (Tmax) of CSL312 in subjects with
C1-INH HAE during Treatment Period 1
9. Terminal elimination half-life (T1/2) of CSL312 in subjects with C1-
INH HAE during Treatment Period 1
10. Total systemic clearance (CLtot) of CSL312 in subjects with C1-INH
HAE during Treatment Period 1
11 Volume of distribution during the elimination phase (Vz) of CSL312
in subjects with C1-INH HAE during Treatment Period 1
12. The number of subjects with C1-INH HAE with adverse events,
serious adverse events, adverse events of special interest, injection site
reactions, inhibitory antibodies to CSL312, clinically significant
abnormalities in laboratory assessment that are reported as adverse
events during Treatment Period 1
13. The percentage of subjects with C1-INH HAE with adverse events,
serious adverse events, adverse events of special interest, injection site
reactions, inhibitory antibodies to CSL312, clinically significant abnormalities in laboratory assessment that are reported as adverse events during Treatment Period 1 |
|
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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Israel |
United States |
Denmark |
Germany |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 21 |