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 ALXN1840 administered for 48 weeks, compared to standard of care (SoC), on copper (Cu) control in WD subjects aged 12 and older. Copper control will be assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper (NCC) levels. For WTX101-treated subjects, the NCC level will be corrected for the amount of Cu bound to the WTX101 tripartite complex (TPC) (NCCcorrected). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to:
-Establish the safety and tolerability of individualized dosing of ALXN1840;
-Evaluate the effects of ALXN1840 on hepatic status;
-Evaluate the effects of ALXN1840 on disability status;
-Evaluate the effects of ALXN1840 on neurological status;
-Evaluate the global effects of ALXN1840 on clinical symptoms;
-Evaluate the effects of ALXN1840 on the NCC responder rate;
please see the study protocol for details |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Established diagnosis of WD by Leipzig-Score > 4 documented by testing as outlined in the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines;
-12 years of age or older at time of informed consent/assent;
- Willing and able to give written informed consent and comply with the study visit schedule. For patients < 18 years of age; patient's legal guardian must be willing and able to give written informed consent and the patient must be willing to give written informed assent (if applicable as determined by the central or local Institutional Review Board [IRB]/ Institutional (or Independent) Ethics Committee [IEC]). If allowable per local regulations, a patients’ Legally Acceptable Representative may provide informed consent if a patient is unable to do so.
-Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator.;
-Willing to withhold treatment with SoC for >48 hours immediately prior to first study assessment on Day 1;
-Adequate venous access to allow collection of required blood samples;
- Willing to avoid use of vitamins and/or minerals containing Cu, Zn, or molybdenum (Mo) throughout the study duration;
-Willing to avoid intake of foods and drinks with high contents of Cu throughout the study duration;
-Female patients of childbearing potential, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception starting at least 6 weeks before the Day 1 visit and continuing through 28 days after the last dose of study drug (either ALXN1840 or SoC). Male patients, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception beginning at the Day 1 visit and continuing through 90 days after the last dose of study drug (either ALXN1840 or SoC).
please see the study protocol for details |
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E.4 | Principal exclusion criteria |
- Decompensated hepatic cirrhosis;
- MELD score greater than 13;
- Participation in a clinical study of an experimental or unapproved/unlicensed therapy at the same time or within the 4 weeks prior to this Screening Visit;
- Pregnant (or women who are planning to become pregnant) or lactating women;
- Major systemic disease or other illness that would, in the opinion of the Investigator, compromise subject safety or interfere with the collection or interpretation of study results;
- Modified Nazer score >7
- Hemoglobine < 9 g/dL
- Alanine aminotransferase >2 × ULN for subjects treated for >28 days with WD therapy (Cohort 1);
- Alanine aminotransferase Alanine aminotransferase > 5 × ULN for treatment naïve subjects or subjects who have been treated for ≤ 28 days (Cohort 2);
- Patients with end-stage renal disease on dialysis (CKD 5) or creatinine clearance < 30 mL/min
please see study protocol for more details |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy assessment will be control of free Cu, measured as the percent change from baseline (Day 1) to 48 weeks in NCC levels. For ALXN1840-treated subjects, the NCC level will be corrected for the amount of Cu bound to the ALXN1840 TPC. |
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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) |
The secondary endpoints include the following:
a. Change from baseline in hepatic status at 48 weeks assessed by MELD score;
b. Change from baseline to 48 weeks in UWDRS Part II score;
c. Change from baseline to 48 weeks in UWDRS Part III score;
d. Change from baseline to 48 weeks in the CGI-I and CGI-S; and
e. NCC responder rate at 48 weeks. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Penicillamine, Trientine dihydrochloride and Zinc |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Austria |
Belgium |
Brazil |
Canada |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Hong Kong |
Hungary |
Israel |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Poland |
Portugal |
Russian Federation |
Serbia |
Singapore |
Spain |
Sweden |
Taiwan |
Turkey |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |