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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03403205
Recruitment Status : Active, not recruiting
First Posted : January 18, 2018
Last Update Posted : May 9, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Wilson Disease Drug: ALXN1840 Drug: SoC Therapy Phase 3

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 215 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 15, 2018
Actual Primary Completion Date : February 24, 2021
Estimated Study Completion Date : February 28, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Wilson Disease

Arm Intervention/treatment
Experimental: 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.

Drug: ALXN1840
ALXN1840 administered orally in 15 mg tablets
Other Names:
  • Formerly named WTX101
  • Tiomolibdic acid
  • Tiomolibdate choline

Active Comparator: 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.
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.




Primary Outcome Measures :
  1. Daily Mean Area Under The Effect-time Curve (AUEC) Of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) [ Time Frame: Baseline to 48 weeks ]

Secondary Outcome Measures :
  1. Change From Baseline In cNCC In Plasma. [ Time Frame: Baseline, 48 weeks ]
  2. Number Of Participants With Treatment-emergent Adverse Events [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  3. Effects of ALXN1840 on hepatic status [ Time Frame: Baseline (Day 1) to 48 weeks ]
  4. Effects of ALXN1840 on disability status [ Time Frame: Baseline (Day 1) to 48 weeks ]
  5. Effects of ALXN1840 on neurological status, as assessed by UWDRS Part III individual items/subscales (arising from a chair, gait, handwriting, and speech) [ Time Frame: Baseline (Day 1) to 48 weeks ]
  6. Global effects of ALXN1840 on clinical symptoms as assessed by the Investigator on the Clinical Global Impression-Improvement Scale (CGI-I) and the Clinical Global Impression-Severity Scale (CGI-S) [ Time Frame: Baseline (Day 1) to 48 weeks ]
  7. Effects of ALXN1840 on NCC responder rate [ Time Frame: Baseline (Day 1) to 48 weeks ]
  8. Change From Baseline In The Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  9. Change From Baseline In UWDRS Part III Total Score And Individual Items/Subscales (Arising From A Chair, Gait, Handwriting, And Speech) [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  10. Clinical Global Impression-Improvement Scale (CGI-I) [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  11. Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  12. Change From Baseline In Model For End-Stage Liver Disease (MELD) Score [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  13. Change From Baseline In Calculated NCC (cNCC) In Plasma [ Time Frame: Baseline (Day 1), 48 weeks ]
  14. cNCC Responder Rate [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Established diagnosis of WD by Leipzig-Score ≥ than 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

Key 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03403205


Locations
Show Show 54 study locations
Sponsors and Collaborators
Alexion Pharmaceuticals
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03403205    
Other Study ID Numbers: WTX101-301
First Posted: January 18, 2018    Key Record Dates
Last Update Posted: May 9, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Alexion Pharmaceuticals:
Wilson Disease
ALXN1840
Additional relevant MeSH terms:
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Hepatolenticular Degeneration
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
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors
Metabolic Diseases
Choline
Lipotropic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Agents
Lipid Regulating Agents
Nootropic Agents