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Efficacy and Safety of ALXN1840 (Formerly Named WTX101) Administered for 48 Weeks Versus Standard of Care in Patients With Wilson Disease With an Extension Period of up to 60 Months

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ClinicalTrials.gov Identifier: NCT03403205
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : September 30, 2019
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 September 30, 2019
Actual Study Start Date  ICMJE February 15, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
Evaluate the efficacy of ALXN1840 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 ]
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 Complete list of historical versions of study NCT03403205 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Safety and tolerability of individualized dosing of ALXN1840 by descriptive statistics [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
  • Effects of ALXN1840 on hepatic status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
  • Effects of ALXN1840 on disability status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
  • Effects of ALXN1840 on neurological status [ Time Frame: Change from 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: Change from baseline (Day 1) to 48 weeks ]
  • Effects of ALXN1840 on NCC responder rate [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
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 (Formerly Named WTX101) Administered for 48 Weeks Versus Standard of Care in Patients With Wilson Disease With an Extension Period of up to 60 Months
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 With an Extension Period of Up To 60 Months
Brief Summary The purpose of this study is to evaluate the efficacy of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in WD patients aged 12 and older.
Detailed Description Not Provided
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 Name: Formerly named WTX101
  • Drug: SoC Therapy
    Depending on the site/region,subjects 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 15-60 mg
    Intervention: Drug: ALXN1840
  • Active Comparator: Standard of Care (SoC) Medication
    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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
180
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2018)
102
Estimated Study Completion Date  ICMJE February 2026
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

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

Exclusion:

  • Decompensated hepatic cirrhosis
  • MELD score > 13
  • Modified Nazer score > 7
  • Clinically significant GI bleed within past 3 months
  • Alanine aminotransferase > 2 X upper limit of normal (ULN) for patients treated for > 28 days with WD therapy (Cohort 1)
  • Alanine aminotransferase > 5 X ULN for treatment naïve patients or patients who have been treated for < or = to 28 days (Cohort 2)
  • Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care
  • Hemoglobin < 9 g/dL
  • 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
  • Patients with end-stage renal disease on dialysis (CKD 5) or creatinine clearance < 30 mL/min
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: Alexion Pharmaceuticals, Inc. +1-855-752-2356 clinicaltrials@alexion.com
Listed Location Countries  ICMJE Australia,   Austria,   Czechia,   France,   Germany,   Hungary,   Israel,   Japan,   Poland,   Serbia,   Spain,   United Kingdom,   United States
Removed Location Countries 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 Not Provided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Eugene Swenson, MD, PhD Alexion Pharmaceuticals
PRS Account Alexion Pharmaceuticals
Verification Date September 2019

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