Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease

NCT03403205 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: WTX101-3012017-004135-36
• Study Type: interventional
• Target: 214
• Locations: 21 countries
• Sites: 53

Brief Summary

The study will evaluate the efficacy and safety of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson Disease (WD) participants aged 12 and older in the Primary Evaluation Period. In addition, efficacy and safety will be evaluated during an optional 60-month Extension Period.

Conditions

Wilson Disease

Keywords

Wilson Disease; ALXN1840; Copper

Outcome Measures

Primary Outcomes (1)

• Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)

  dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).

  Baseline to Week 48

Secondary Outcomes (11)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Baseline up to Week 48

• Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48

  Baseline, Week 48

• Change From Baseline in UWDRS Part III Total Score at Week 48

  Baseline, Week 48

• Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48

  Baseline, Week 48

• Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48

  Baseline, Week 48

Study Arms (2)

ALXN1840

EXPERIMENTAL

ALXN1840 was administered orally for 48 weeks at doses ranging from 15 milligrams (mg) every other day (QOD) up to a titrated dose of 60 mg daily. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.

Drug: ALXN1840

Standard of Care (SoC) Medication

ACTIVE COMPARATOR

SoC medication was administered for 48 weeks. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.

Drug: SoC Therapy

Interventions

ALXN1840 DRUG

ALXN1840 administered orally in 15 mg tablets

Also known as: Formerly named WTX101, Tiomolibdic acid, Tiomolibdate choline, Bis-choline tetrathiomolybdate

ALXN1840

SoC Therapy DRUG

Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.

Standard of Care (SoC) Medication

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Established diagnosis of WD by Leipzig-Score ≥ 4
• Female participants of childbearing potential, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception starting at least 6 weeks before the Day 1 visit and continuing through 28 days after the last dose of either ALXN1840 or SoC
• Male participants, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception beginning at Day 1 visit and continuing through 90 days after last dose of either ALXN1840 or SoC

You may not qualify if:

• Decompensated hepatic cirrhosis
• MELD score \> 13
• Modified Nazer score \> 7
• Clinically significant gastrointestinal bleed within past 3 months
• Alanine aminotransferase \> 2 X upper limit of normal (ULN) for participants treated for \> 28 days with WD therapy (Cohort 1)
• Alanine aminotransferase \> 5 X ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days (Cohort 2)
• Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care
• Hemoglobin \< 9 grams/deciliter
• History of seizure activity within 6 months prior to informed consent
• Pregnant (or women who are planning to become pregnant) or breastfeeding women
• Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus or seropositivity for human immunodeficiency virus (HIV)
• Previous treatment with tetrathiomolybdate
• Participants with end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance \< 30 milliliter/minute

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (56)

Research Site

Los Angeles, California, 90095, United States

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New Haven, Connecticut, 06510, United States

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Chicago, Illinois, 60611, United States

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Ann Arbor, Michigan, 48109, United States

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Houston, Texas, 77030, United States

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Seattle, Washington, 98105, United States

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Adelaide, 5000, Australia

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Concord, 2139, Australia

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Parkville, 3050, Australia

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Parkville, VIC 3052, Australia

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Graz, 8036, Austria

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Innsbruck, 6020, Austria

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Vienna, 1090, Austria

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Toronto, Ontario, M5G 2C4, Canada

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Prague, 128 08, Czechia

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Århus N, 8200, Denmark

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Bron, 69667, France

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Paris, 75010, France

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Hamburg, 20099, Germany

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Heidelberg, 69120, DE, Germany

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Leipzig, 04103, Germany

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Hong Kong, 852, Hong Kong

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Budapest, 1083, Hungary

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Jerusalem, 9112001, Israel

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Ramat Gan, 5265601, Israel

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Chiba, 266-0007, Japan

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Kumamoto, 860-8556, Japan

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Kurume-shi, 830-0011, Japan

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Matsuyama, 790-0024, Japan

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Meguro-ku, 153-8515, Japan

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Sapporo, 063-0005, Japan

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Takatsuki-shi, 569-8686, Japan

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Yokohama, 230-8765, Japan

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Grafton, 1010, New Zealand

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Warsaw, 02-957, Poland

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Warsaw, 04-730, Poland

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Moscow, 115446, Russia

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Moscow, 117292, Russia

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Moscow, 119021, Russia

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Nizhny Novgorod, 603005, Russia

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Saint Petersburg, 194017, Russia

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Belgrade, 11000, Serbia

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Singapore, 169608, Singapore

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Daegu, 41944, South Korea

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Barcelona, 08036, Spain

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Málaga, 29011, Spain

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Sabadell, 08208, Spain

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Taipei, 10002, Taiwan

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Taoyuan, 333, Taiwan

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Ankara, 06230, Turkey (Türkiye)

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Istanbul, 34010, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Edgbaston, B15 2WB, United Kingdom

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Guildford, GU2 7WG, United Kingdom

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London, SE5 9RS, United Kingdom

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Related Links

• Related Info

MeSH Terms

Conditions

Hepatolenticular Degeneration

Interventions

tetrathiomolybdate

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

Results Point of Contact

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

clinicaltrials@alexion.com

+1 855-752-2356

Study Officials

• Eugene S. Swenson, M.D., Ph.D.

  Alexion Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2017
• First Posted: January 18, 2018
• Study Start: February 22, 2018
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: June 17, 2024
• Results First Posted: October 10, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

RU (5); SG (1); NZ (1); DK (1); FR (2); AU (4); US (6); HK (1); JP (8); CA (1); PL (2); SE (1); KR (1); DE (3); IL (2); GB (3); TU (4); TW (2); HU (1); ES (3); CZ (1)