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

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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

Tracking Information
First Submitted Date  ICMJE December 19, 2017
First Posted Date  ICMJE January 18, 2018
Last Update Posted Date May 9, 2022
Actual Study Start Date  ICMJE February 15, 2018
Actual Primary Completion Date February 24, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2021)
Daily Mean Area Under The Effect-time Curve (AUEC) Of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) [ Time Frame: Baseline to 48 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
Evaluate the efficacy of WTX101 using standard of care as comparator and copper as the control assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper levels [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
Evaluate the efficacy of WTX101 administered for 48 weeks, compared to standard of care, on copper control in Wilson Disease subjects aged 18 and older. Copper control will be assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper levels. For WTX101-treated subjects, the non-ceruloplasmin-bound copper level will be corrected for the amount of copper bound to the WTX101 tripartite complex.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2022)
  • Change From Baseline In cNCC In Plasma. [ Time Frame: Baseline, 48 weeks ]
  • 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 ]
  • Effects of ALXN1840 on hepatic status [ Time Frame: Baseline (Day 1) to 48 weeks ]
  • Effects of ALXN1840 on disability status [ Time Frame: Baseline (Day 1) to 48 weeks ]
  • 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 ]
  • 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 ]
  • Effects of ALXN1840 on NCC responder rate [ Time Frame: Baseline (Day 1) to 48 weeks ]
  • 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 ]
  • 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 ]
  • Clinical Global Impression-Improvement Scale (CGI-I) [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
  • 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 ]
  • 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 ]
  • Change From Baseline In Calculated NCC (cNCC) In Plasma [ Time Frame: Baseline (Day 1), 48 weeks ]
  • cNCC Responder Rate [ Time Frame: Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2018)
  • Safety and tolerability of individualized dosing of WTX101 by descriptive statistics via the Safety Analysis Set dataset [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Safety and tolerability will be determined over the course of the study period by descriptive statistics via the Safety Analysis Set dataset. This dataset includes all subjects who received at least 1 dose of randomized treatment. Subjects will be summarized according to the treatment actually received.
  • Effects of WTX101 on hepatic status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on hepatic status assessed by the Model for End-Stage Liver Disease (MELD) score. The MELD uses the subject's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. It is calculated according to the following formula: MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43.
  • Effects of WTX101 on disability status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on disability status assessed by the Unified WD Rating Scale (UWDRS) Part II which consists of a historical review of daily activity items and is reported by the subject or family.
  • Effects of WTX101 on neurological status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on neurological status assessed by the Unified WD Rating Scale (UWDRS) Part III which consists of a neurological examination performed by a blinded neurologist.
  • Global effects of WTX101 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: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the global effects of WTX101 on clinical symptoms performed by the Investigator using a composite assessment which include the Clinical Global Impression-Improvement Scale (a 7-point scale that assess how much the subject's illness has improved or worsened relative to a baseline and rated from 1 to 7) and the Clinical Global Impression-Severity Scale (a 7-point scale that assess severity of a subject's illness relative to a baseline and rated from 1 to 7).
  • Effects of WTX101 on NCC responder rate [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on the NCC responder rate
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of ALXN1840 (Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
Official Title  ICMJE 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
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.
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Wilson Disease
Intervention  ICMJE
  • Drug: ALXN1840
    ALXN1840 administered orally in 15 mg tablets
    Other Names:
    • Formerly named WTX101
    • Tiomolibdic acid
    • Tiomolibdate choline
  • 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.
Study Arms  ICMJE
  • 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.

    Intervention: Drug: ALXN1840
  • 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.
    Intervention: Drug: SoC Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 6, 2020)
215
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2018)
102
Estimated Study Completion Date  ICMJE February 28, 2026
Actual Primary Completion Date February 24, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   Czechia,   Denmark,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Japan,   Korea, Republic of,   New Zealand,   Poland,   Russian Federation,   Serbia,   Singapore,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Belgium,   Italy
 
Administrative Information
NCT Number  ICMJE NCT03403205
Other Study ID Numbers  ICMJE WTX101-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Current Responsible Party Alexion Pharmaceuticals
Original Responsible Party Wilson Therapeutics AB
Current Study Sponsor  ICMJE Alexion Pharmaceuticals
Original Study Sponsor  ICMJE Wilson Therapeutics AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP