Efficacy and Safety Study of WTX101 (ALXN1840) in Adult Wilson Disease Patients

NCT02273596 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: WTX101-201
• Study Type: interventional
• Target: 29
• Locations: 5 countries
• Sites: 9

Brief Summary

The main purpose of the study was to evaluate the efficacy of ALXN1840 (formerly WTX101) for 24 weeks on non-ceruloplasmin-bound copper (NCC) concentrations adjusted for molybdenum plasma concentration in participants newly diagnosed with Wilson Disease (WD) who were aged 18 and older and who had NCC concentrations within or above the reference range at the time of enrollment in the study. The study consisted of a 24-week Treatment Period, followed by a planned 36-month Extension Period.

Conditions

Wilson Disease

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants With Normalized Concentrations Of NCC

  Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole \[μmol\]l/liter \[L\]\]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.

  Week 24

Secondary Outcomes (22)

• Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24

  Baseline, Week 24

• Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC

  Up to last assessment (up to Week 176)

• Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24

  Baseline, Week 24

• Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24

  Baseline, Week 24

• Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24

  Baseline, Week 24

Study Arms (1)

ALXN1840

EXPERIMENTAL

Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligram (mg) per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks. Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range. ALXN1840 could have been received for up to 36 months in the Extension Period.

Drug: ALXN1840

Interventions

ALXN1840 DRUG

Individualized oral doses of ALXN1840.

Also known as: WTX101

ALXN1840

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator.
• Newly established diagnosis of WD by Leipzig-Score ≥ 4 documented by testing as outlined in 2012 European Association for the Study of the Liver Wilson Disease Clinical Practice Guidelines.
• NCC levels within or above the normal reference range (0.8 to 2.3 micromole).
• Willing to undergo 48 hour washout from current WD treatment

You may not qualify if:

• Treatment for greater than 24 months for WD with chelation therapy (for example, penicillamine, trientine hydrochloride) or zinc therapy.
• Decompensated hepatic cirrhosis.
• Model for End-Stage Liver Disease score \> 11.
• Modified Nazer score \> 6.
• Gastrointestinal bleed within past 6 months.
• Alanine aminotransferase \> 5 x upper limit of normal.
• Marked neurological disease requiring either nasogastric feeding or intensive in-patient medical care.
• Severe anemia with a hemoglobin \< 9 grams/deciliter.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (9)

Clinical Trial Site

Los Angeles, California, 90095, United States

Location

Clinical Trial Site

New Haven, Connecticut, 06519, United States

Location

Clinical Trial Site

Chicago, Illinois, 60611, United States

Location

Clinical Trial Site

Ann Arbor, Michigan, 48109, United States

Location

Clinical Trial Site

Vienna, 1090, Austria

Location

Clinical Trial Site

Heidelberg, 69120, Germany

Location

Clinical Trial Site

Warsaw, 02-957, Poland

Location

Clinical Trial Site

Guildford, Surrey, GU27XX, United Kingdom

Location

Clinical Trial Site

Birmingham, B15 2TH, United Kingdom

Location

Related Publications (1)

• Weiss KH, Askari FK, Czlonkowska A, Ferenci P, Bronstein JM, Bega D, Ala A, Nicholl D, Flint S, Olsson L, Plitz T, Bjartmar C, Schilsky ML. Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):869-876. doi: 10.1016/S2468-1253(17)30293-5. Epub 2017 Oct 5.

  PMID: 28988934 RESULT

MeSH Terms

Conditions

Hepatolenticular Degeneration

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Due to low chromatographic resolution of data, quantitative analysis for speciation profiling, as had been planned in the protocol, was not feasible.

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Study Officials

• Eugene Swenson, MD, PhD

  Alexion Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: October 24, 2014
• Study Start: November 24, 2014
• Primary Completion: October 27, 2016
• Study Completion: November 7, 2018
• Last Updated: September 29, 2021
• Results First Posted: September 29, 2021

Record last verified: 2021-09

Locations

US (4); PL (1); GB (2); DE (1); AU (1)