Study to Evaluate the Efficacy and Safety of ALXN1840 in pPtients with Wilson Disease.

• Register: EUCTR
• Last refreshed on: 9 November 2020
• Main ID: EUCTR2017-004135-36-NL
• Date of registration: 16/10/2019
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc
• Public title: Study to Evaluate the Efficacy and Safety of ALXN1840 in pPtients with Wilson Disease.
• Scientific title: A Phase 3, Randomized, Rater-Blinded, Multi-Center Study To Evaluate The Efficacy And Safety Of ALXN1840 Administered For 48 Weeks Versus Standard Of Care In Patients With Wilson Disease Aged 12 Years And Older With An Extension Period Of Up To 60 Months
• Date of first enrolment: 30/03/2020
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004135-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Rater Blinded If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Penicillamine, Trientine dihydrochloride and Zinc Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, Colombia, Croatia, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Russian Federation, Serbia, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

• Name: European Clinical Trial Information
• Affiliation: Alexion Europe SAS

Key inclusion & exclusion criteria

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.
-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 must be willing to follow guidance for highly effective contraception;

please see the study protocol for details
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

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 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


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 Name: ALXN1840
Pharmaceutical Form: Tablet
INN or Proposed INN: Not applied
CAS Number: 649749-10-0
Current Sponsor code: ALXN1840
Other descriptive name: BIS-CHOLINE TETRATHIOMOLYBDATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Pharmaceutical Form: Tablet
INN or Proposed INN: PENICILLAMINE
CAS Number: 52-67-5

Pharmaceutical Form: Capsule
INN or Proposed INN: TRIENTINE DIHYDROCHLORIDE
CAS Number: 38260-01-4
Concentration unit: g gram(s)
Concentration type: range
Concentration number: 1.2-2.4-(4-8 capsules)

Pharmaceutical Form: Capsule
INN or Proposed INN: ZINC ACETATE DIHYDRATE
CAS Number: 5970-45-6
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 150-3 times daily

Primary Outcome(s)

Main Objective: 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).

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.

Secondary Objective: 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

Timepoint(s) of evaluation of this end point: 48 weeks

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: 48 weeks

Secondary ID(s)

WTX101-301

2017-004135-36-GB

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc