A clinical trial in adult Wilson Disease Patients to evaluate efficacy and safety of WTX101 following administration for 24 weeks and an extension phase of 36 months.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2014-001703-41-DE
• Date of registration: 05/06/2014
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, INC.
• Public title: A clinical trial in adult Wilson Disease Patients to evaluate efficacy and safety of WTX101 following administration for 24 weeks and an extension phase of 36 months.
• Scientific title: A Phase 2, Multi-centre, Open-label, Study to Evaluate the Efficacy and Safety of WTX101 Administered for 24 Weeks in Newly Diagnosed Wilson Disease Patients Aged 18 and Older with an Extension Phase of 36 Months
• Date of first enrolment: 18/08/2014
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001703-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Germany, Poland, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Pharmaceuticals, Inc.

• Name: European Clinical Trial Information
• Affiliation: Alexion Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

Wilson Disease
MedDRA version: 20.0 Level: LLT Classification code 10047988 Term: Wilson's disease System Organ Class: 100000004850

Intervention(s)

Product Code: WTX101
Pharmaceutical Form: Tablet
INN or Proposed INN: none
CAS Number: 64-9749-10-0
Current Sponsor code: WTX101
Other descriptive name: bis-choline TETRATHIOMOLYBDATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

Main Objective: 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.

Primary end point(s): Non-ceruloplasmin-bound copper (NCC) levels adjusted for molybdenum (Mo) plasma concentration

Secondary Objective: - 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

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: 24 weeks, variable

Secondary ID(s)

WTX101-201

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date:
Contact: