E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary angiodema (HAE) type I and II are genetic disorders that are associated with a deficiency in C1 esterase-inhibitor |
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E.1.1.1 | Medical condition in easily understood language |
Hereditary angiodema type I and II |
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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 | 20.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of the study are to evaluate the clinical efficacy and PK of SC CSL830 in the prophylactic treatment of HAE in Japanese subjects |
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E.2.2 | Secondary objectives of the trial |
• To further characterize the clinical efficacy of the SC CSL830
• To demonstrate the safety and tolerability of SC CSL830
• To evaluate C1-INH functional activity and C1-INH antigen (PK), and C4 antigen (pharmacodynamics [PD]) during CSL830 treatment
• To evaluate subject-reported Angioedema Quality of Life (AEQoL) outcomes, and subject and investigator global assessments of response to therapy (SGART and IGART) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males or females aged 12 years or older.
• Japanese with a confirmed clinical diagnosis of HAE type I or II.
• At least 4 HAE attacks over a consecutive 2-month period as documented in the subject’s medical records in the 3 months before the Screening Visit
• C1-INH functional activity of less than 50% norm, AND C4 antigen concentration below the laboratory reference range
• During their participation in the Run-In Period experienced ≥ 2 HAE attacks within any consecutive 4-week period, OR experienced ≥ 1 HAE attack during the first 2 weeks
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E.4 | Principal exclusion criteria |
• History of arterial or venous thrombosis requiring anticoagulant therapy, or current, clinically significant prothrombotic risk
• Known malignancies at the time of the Screening Visit
• Have a history of allergic reaction to C1-INH products, including Cinryze and Berinert P or other blood products
• Unable to discontinue use of intravenous (IV) C1-INH for routine prophylaxis against HAE attacks by Day 1 of the Run-in Period or plans to use IV C1-INH for routine prophylaxis against HAE attacks by Day 1 of the Run-in Period
• Assessed by the investigator as unable to have their HAE adequately managed with on-demand treatment, administered either independently or with assistance
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E.5 End points |
E.5.1 | Primary end point(s) |
-Time-normalized number of HAE attacks during treatment with CSL830.
-C1-INH functional activity (PK: AUC0-tau, AUC0-last, Cmax, Tmax, T1/2) after the last dose of CSL830 Treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
-Up to 14 weeks
-Up to 11 days after the last dose
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E.5.2 | Secondary end point(s) |
-The percentage of subjects who achieved ≥ 90%, ≥ 70%, and ≥ 50% relative reduction of monthly HAE attack rate.
-The relative reduction in the time-normalized number of rescue medication uses.
-The number of reported adverse Events.
-Percentage of subjects reporting adverse events (AEs) and injection site reactions that begin within 24 hours of CSL830 administration.
-Mean trough C1-INH functional activity during treatment with CSL830.
-Mean trough C1-INH and C4 antigens during treatment with CSL830.
-Subject-reported Angioedema Quality of Life (AEQoL) outcome scores
-Subject-reported Global Assessments of Reponse to Therapy outcomes (SGART)
-Investigator-reported Global Assessments of Reponse to Therapy outcomes (IGART)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
-Up to 14 weeks
-Up to 14 weeks
-Up to 18 weeks
-Up to 24 hours after dose
-Up to 16 weeks
-Up to 16 weeks
-Up to 16 weeks
-Up to 16 weeks
-Up to 16 weeks
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 0 |