E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Angioedema (HAE) type I and II |
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E.1.1.1 | Medical condition in easily understood language |
HAE is a genetic disorder with 3 known types.Types I/II are associated with C1 esterase inhibitor deficiencies.Type III extremely rare is associated with normal C1 esterase inhibitor and disease state |
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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 | 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 |
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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 demonstrate the clinical efficacy of SC CSL830 in the prophylactic treatment of HAE.To compare the clinical efficacy of 2 doses of SC
CSL830.
The comparison of the clinical efficacy of the 2 doses of CSL830 will only be done if the clinical efficacy of SC CSL830 in the prophylactic treatment of HAE is shown to be statistically significantly better than placebo.
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E.2.2 | Secondary objectives of the trial |
To further characterize the clinical efficacy of the 2 doses of SC CSL830.
To demonstrate the safety and tolerability of SC CSL830. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Capable of providing written informed consent and willing and able to adhere to all protocol requirements, or the subject’s parent(s) or legally acceptable representative(s) capable of providing written informed consent.
- Male or female
- Aged 12 years or older at the time of providing written informed consent.
- Clinical diagnosis of HAE (type I or II), which will be confirmed by central laboratory testing before inclusion into Treatment Period 1
- HAE attacks over a consecutive 2-month period that required acute treatment, medical attention
- Investigator believes that the subject is willing and able to adhere to all protocol requirements.
- Assessed by the investigator as able to appropriately store study medication and is capable of being trained to administer study medication (by the subject or carer) outside of the study center setting. |
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E.4 | Principal exclusion criteria |
- History of clinically significant arterial or venous thrombosis, or a current history of a clinically significant prothrombotic risk.
- Known incurable malignancies at the time of the Screening visit.
- Any clinical condition that is likely to interfere with evaluation of CSL830 or satisfactory conduct of the study.
- A clinically significant history of poor response to C1-INH therapy for the management of HAE.
- Female subject of childbearing potential either not using or not willing to
use a medically reliable method of contraception or not sexually abstinent during the study, or not surgically sterile.
- Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (ie, estrogen / progesterone containing products) within 3 months before the Screening visit.
- Intention to become pregnant during the course of the study.
- Pregnancy or nursing mother
- Participated in another interventional clinical study within 30 days before Screening or at any time during the study.
- Alcohol, drug or medication abuse within 1 year before Screening.
- Currently receiving a therapy not permitted during the study
- Mental condition rendering the subject (or the subject’s legally acceptable representative[s]) unable to understand the nature, scope and possible consequences of the study.
- Known or suspected hypersensitivity to the investigational product, or to any excipients of the investigational product.
- Previously randomized or participated in the Run-in Period of the current study.
- Employee at the study site, or spouse / partner or relative of the investigator or subinvestigators.
-Any issue that, in the opinion of the investigator, would render the subject unsuitable for participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The time-normalized number of HAE attacks when treated with
CSL830 and when treated with placebo.
- The time-normalized number of HAE attacks between placebo and
the respective CSL830 dose for the 2 doses of CSL830. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The evaluation period will be from the start of Week 3 to the
time point when the subject completes the treatment period (ie, the total assessment period will be up to 14 weeks duration). This is to account for a wash-in / wash-out period of 2 weeks at the start of each treatment period. |
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E.5.2 | Secondary end point(s) |
The proportion of “responders” in the 2 CSL830 dose groups, when defined by the following criteria:
- 50% relative reduction in the time-normalized number of HAE attacks during treatment with CSL830 compared with placebo.
- The time-normalized number of uses of rescue medication
when treated with CSL830 and when treated with placebo.
The secondary safety endpoint is the proportion of subjects with any adverse events (AEs) that begin during or within 24 hours of administration of 40 IU/kg CSL830, 60 IU/kg CSL830 and placebo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The evaluation period for these assessments will start at the beginning of each treatment period and end at Week 14 (Day 92) of each treatment period, or at the time of early escape. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 43 |
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 |
European Union |
Argentina |
Australia |
Canada |
United States |
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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
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The scheduled end of study participation for an individual subject occurs:
1) 1 week aftercompletion of Treatment Period 2 Week 16 (Day 112)
2) 1 week after early exit from Treatment Period 2
3) if a subject is withdrawn early from the study |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |