A Phase 3 clinical study to Evaluate the Efficacy and Safety of ALXN1840 in adult and adolescent patients who suffer from Wilson Disease.

• Register: EUCTR
• Last refreshed on: 10 May 2021
• Main ID: EUCTR2017-004135-36-DE
• Date of registration: 22/12/2017
• Prospective Registration: Yes
• Primary sponsor: Alexion Pharmaceuticals, Inc
• Public title: A Phase 3 clinical study to Evaluate the Efficacy and Safety of ALXN1840 in adult and adolescent patients who suffer from 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: 16/03/2018
• Target sample size: 180
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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: no; 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, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Japan, Korea, Democratic People's 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 (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
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 170
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 > 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


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)

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

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

Secondary Objective: 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

Main Objective: 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

Secondary Outcome(s)

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

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

Secondary ID(s)

WTX101-301

2017-004135-36-GB

Source(s) of Monetary Support

Alexion Pharmaceuticals, Inc

Ethics review

Status: Approved
Approval date: 16/03/2018
Contact: