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

NCT ID: NCT03403205

Last Updated: 2024-06-17

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-22

Study Completion Date

2023-06-30

Brief Summary

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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.

Detailed Description

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The study consists of 2 cohorts. Cohort 1: Participants who have received SoC therapy for \> 28 days and Cohort 2: Participants who are treatment-naïve or who have received SoC therapy for ≤ 28 days.

All enrolled participants were randomized by cohort in a 2:1 ratio to treatment with ALXN1840 or SoC (either as continued therapy in Cohort 1 or as continued or initial therapy in Cohort 2).

Conditions

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Wilson Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.

Study Groups

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ALXN1840

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.

Group Type EXPERIMENTAL

ALXN1840

Intervention Type DRUG

ALXN1840 administered orally in 15 mg tablets

Standard of Care (SoC) Medication

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.

Group Type ACTIVE_COMPARATOR

SoC Therapy

Intervention Type 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.

Interventions

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ALXN1840

ALXN1840 administered orally in 15 mg tablets

Intervention Type DRUG

SoC Therapy

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.

Intervention Type DRUG

Other Intervention Names

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Formerly named WTX101 Tiomolibdic acid Tiomolibdate choline Bis-choline tetrathiomolybdate

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eugene S. Swenson, M.D., Ph.D.

Role: STUDY_DIRECTOR

Alexion Pharmaceuticals, Inc.

Locations

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Los Angeles, California, United States

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New Haven, Connecticut, United States

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Chicago, Illinois, United States

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Ann Arbor, Michigan, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Adelaide, , Australia

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Concord, , Australia

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Parkville, , Australia

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Parkville, , Australia

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Graz, , Austria

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Innsbruck, , Austria

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Vienna, , Austria

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Toronto, Ontario, Canada

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Prague, , Czechia

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Århus N, , Denmark

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Bron, , France

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Paris, , France

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Hamburg, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Hong Kong, , Hong Kong

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Budapest, , Hungary

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Jerusalem, , Israel

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Ramat Gan, , Israel

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Chiba, , Japan

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Kumamoto, , Japan

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Kurume-shi, , Japan

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Matsuyama, , Japan

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Meguro-ku, , Japan

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Sapporo, , Japan

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Takatsuki-shi, , Japan

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Yokohama, , Japan

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Grafton, , New Zealand

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Warsaw, , Poland

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Warsaw, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Saint Petersburg, , Russia

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Belgrade, , Serbia

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Singapore, , Singapore

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Daegu, , South Korea

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Barcelona, , Spain

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Málaga, , Spain

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Sabadell, , Spain

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Taipei, , Taiwan

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Taoyuan, , Taiwan

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Edgbaston, , United Kingdom

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Guildford, , United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Austria Canada Czechia Denmark France Germany Hong Kong Hungary Israel Japan New Zealand Poland Russia Serbia Singapore South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-004135-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WTX101-301

Identifier Type: -

Identifier Source: org_study_id

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