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 control in WD subjects aged 12 and older |
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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 disability status;
-Evaluate the effects of ALXN1840 on neurological status;
-Evaluate the global effects of ALXN1840 on global clinical symptoms;
-Evaluate the effects of ALXN1840 on hepatic status;
-Evaluate the efficacy of ALXN1840 administered for 48 weeks, compared to SoC, on copper control in WD patients aged 12 years and older;
-Evaluate the effects of ALXN1840 on the cNCC responder rate
Please see the study protocol for more 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 (18 years and older in Germany);
- Willing and able to give written informed consent and comply with the study visit schedule. For patients < 18 years of age (or below the age of adulthood under Japanese local law for patients in Japan), patient's legal guardian must be willing and able to give written informed consent;
- 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 copper, zinc, or molybdenum throughout the study duration;
- Willing to avoid intake of foods and drinks with high contents of copper throughout the study duration;
- Female patients of childbearing potential must be willing to follow guidance for highly effective contraception
Please see the study protocol for details |
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E.4 | Principal exclusion criteria |
- Decompensated hepatic cirrhosis;
- MELD score > 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 > 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 (chronic kidney disease stage 5 [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) |
Daily mean area under the effect-time curve (AUEC) of directly measured non-ceruloplasmin-bound copper (dNCC) from 0 to 48 weeks |
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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. Incidence of
• Adverse events/serious adverse events (AE/SAEs)
• Clinical laboratory test data
• Neurological and physical examination findings
• 12-lead electrocardiogram (ECG) data
• Vital signs
b. Change from baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II total score;
c. Change from baseline in UWDRS Part III total score and individual item/subscales (arising from a chair, gait, handwriting, and speech);
d. Clinical Global Impression-Improvement Scale (CGI-I)
e. Change from baseline in Clinical Global Impression-Severity Scale (CGI-S)
f. Change from baseline in Model for End-Stage Liver Disease (MELD) score;
g. Absolute change from baseline (Day 1) to 48 weeks in calculated NCC (cNCC) in plasma and percentage change from baseline in cNCC in plasma. For ALXN1840-treated patients, the cNCC in plasma will be corrected for the amount of copper bound to the ALXN1840 tripartite complex (TPC) (cNCCcorrected);
h. cNCC 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 | 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 | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 |
Brazil |
Canada |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Singapore |
Taiwan |
United States |
Russian Federation |
Turkey |
Serbia |
Austria |
Belgium |
Czechia |
Denmark |
France |
Germany |
Hungary |
Netherlands |
Poland |
Portugal |
Spain |
Sweden |
United Kingdom |
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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 |