E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10047988 |
E.1.2 | Term | Wilson's disease |
E.1.2 | System Organ Class | 100000004850 |
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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 objective is to evaluate the efficacy of WTX101 for 24 weeks on non-ceruloplasmin-bound copper (NCC) levels adjusted for molybdenum (Mo) plasma concentration in newly diagnosed Wilson Disease (WD) patients aged 18 and older with NCC levels within or above the normal reference range at the time of enrolment. |
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E.2.2 | Secondary objectives of the trial |
- Establish the safety and tolerability of individualised dosing of WTX101 over the course of the study period - Evaluate: change in and time to normalisation of NCC levels adjusted for Mo plasma concentration; the effects of WTX101 on neurological status using the UWDRS (neurological subscore; parts I, II and III); the effects of WTX101 on psychiatric status using M.I.N.I. Tracking; the global effects of WTX101 on clinical symptoms as assessed by the Investigators on the CGI scale items 1 (severity of illness) and 2 (global improvement); the effects of WTX101 on the following QoL / PRO endpoint measures: EQ5D, MAQ-8 and the TSQM, the effects of WTX101 on hepatic measures - Analyse copper endpoints (exchangeable copper, speciation profiling, and 24-hour urinary copper) - Collect PK data on WTX101 in this patient population based on the measurement of plasma total Mo - Evaluate the durability, and establish long-term safety and efficacy of WTX101 in a 36 month Extension Phase |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Willing and able to give informed consent for participation in the study. Male or female patients, aged 18 years or older as of signing the ICF. Able to understand and willing to comply with study procedures, restrictions and requirements, as judged by the Investigator. Newly established diagnosis of Wilson Disease by Leipzig-Score >/=4 (Ferenci et al 2003) documented by testing as outlined in 2012 EASL WD Clinical Practice Guidelines. NCC levels above or within the normal reference range (0.8-2.3 µM). Willing to undergo 48 hour washout from current Wilson Disease treatment. |
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E.4 | Principal exclusion criteria |
Treatment for greater than 24 months for Wilson Disease with chelation therapy (i.e. penicillamine, trientine hydrochloride) or zinc therapy. Decompensated hepatic cirrhosis. Model for End-Stage Liver Disease (MELD) score > 11. Modified Nazer score > 6 (Dhawan et al. Liver Transplant 2005). GI bleed within past 6 months. ALT > 5x upper limit of normal (ULN). Marked neurological disease requiring either nasogastric (NG) feeding or intensive in-patient medical care. Severe anaemia with a haemoglobin < 9 g/dL. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Non-ceruloplasmin-bound copper (NCC) levels adjusted for molybdenum (Mo) plasma concentration |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Change in NCC levels adjusted for Mo plasma concentration - Time to normalisation of NCC adjusted for Mo plasma concentration - Change in exchangeable copper during 24 weeks of treatment - Change in speciation profiling (Mo, Cu and protein complex profiling with SEC) during 24 weeks of treatment - Change in 24-hour urinary copper during 24 weeks of treatment - Changes in hepatic measures (ALT, AST, INR and bilirubin) - Changes in neurological status using the UWDRS (neurological subscore; parts I, II and III) and additionally: - Number of patients that deteriorate = increase ≥ 4 (part III of neurological sub-score) or increase ≥ 1 (part II of neurological sub-score). - Number of patients that improve = decrease ≥ 4 (part III of neurological sub-score) or decrease ≥ 1 (part II of neurological sub-score). - Changes in psychiatric status using M.I.N.I. Tracking - Changes in the global effects of WTX101 on clinical symptoms assessed by the Investigators on the CGI scale items 1 (severity of illness) and 2 (global improvement) - Absolute changes in QOL / PRO measures EQ5D, MAQ-8, TSQM - Pharmacokinetic (PK) data based on measurement of plasma total molybdenum (Mo) - Durability and long term efficacy of WTX101 in a 36 month Extension Phase. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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) | 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 | 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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 |
Austria |
Germany |
Poland |
United Kingdom |
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |