A Phase 2, Multi-centre, Open-label, Study to Evaluate the Efficacy and Safety of WTX101 Administered for 24 Weeks in Newly Diagnosed Wilson Disease Patients Aged 18 and Older With an Extension Phase of 36 Months
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Percentage Of Participants With Normalized Concentrations Of NCC
研究概览
简要总结
The main purpose of the study was to evaluate the efficacy of ALXN1840 (formerly WTX101) for 24 weeks on non-ceruloplasmin-bound copper (NCC) concentrations adjusted for molybdenum plasma concentration in participants newly diagnosed with Wilson Disease (WD) who were aged 18 and older and who had NCC concentrations within or above the reference range at the time of enrollment in the study. The study consisted of a 24-week Treatment Period, followed by a planned 36-month Extension Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator.
- •Newly established diagnosis of WD by Leipzig-Score ≥ 4 documented by testing as outlined in 2012 European Association for the Study of the Liver Wilson Disease Clinical Practice Guidelines.
- •NCC levels within or above the normal reference range (0.8 to 2.3 micromole).
- •Willing to undergo 48 hour washout from current WD treatment
排除标准
- •Treatment for greater than 24 months for WD with chelation therapy (for example, penicillamine, trientine hydrochloride) or zinc therapy.
- •Decompensated hepatic cirrhosis.
- •Model for End-Stage Liver Disease score >
- •Modified Nazer score >
- •Gastrointestinal bleed within past 6 months.
- •Alanine aminotransferase > 5 x upper limit of normal.
- •Marked neurological disease requiring either nasogastric feeding or intensive in-patient medical care.
- •Severe anemia with a hemoglobin < 9 grams/deciliter.
研究组 & 干预措施
ALXN1840
Treatment Period: ALXN1840 at individualized doses ranging from 15 to 60 milligram (mg) per day. Dose increases or dose reductions were dependent on the individual NCC concentrations adjusted for Mo plasma concentration. ALXN1840 may have been administered every other day, once daily, or twice daily, depending on individualized dosing regimen, for 24 weeks.
Extension Period: Participants continued the same ALXN1840 daily dose maintained at Week 24 of the Treatment Period and the same dosing regimen. During the Extension Period, no up-titration was made unless NCC concentrations adjusted for Mo plasma concentration did not remain stable within (or below) the reference range. ALXN1840 could have been received for up to 36 months in the Extension Period.
干预措施: ALXN1840 (Drug)
结局指标
主要结局
Percentage Of Participants With Normalized Concentrations Of NCC
时间窗: Week 24
Normalized concentrations of NCC was defined as who achieving or maintaining normalized levels of NCC (0.8 to 2.3 micromole \[μmol\]l/liter \[L\]\]) adjusted for Mo plasma concentration or reaching a reduction of at least 25% in NCC corrected for Mo if above the normal reference range at the time of enrollment. NCC was calculated by subtracting the amount of copper (Cu) bound to ceruloplasmin (CP) from the total plasma Cu concentration. Post-baseline NCC values were adjusted (corrected) to account for Cu bound in tripartite complexes with ALXN1840 and albumin. Descriptive statistics are reported.
次要结局
- Extension Period: Percentage Of Participants With Normalized Concentrations Of NCC(Up to last assessment (up to Week 176))
- Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) At Week 24(Baseline, Week 24)
- Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The European Quality Of Life 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) At Week 24(Baseline, Week 24)
- Change From Baseline In Neurological Status Using The Unified Wilson's Disease Rating Scale (UWDRS) (Neurological Subscore; Part I) At Week 24(Baseline, Week 24)
- Clinical Global Impression-Improvement Scale (CGI-I) At Week 24(Week 24)
- Change From Baseline In Hepatic Laboratory Measure Alanine Aminotransferase (ALT) At Week 24(Baseline, Week 24)
- Change From Baseline In Hepatic Laboratory Measure Aspartate Aminotransferase (AST) At Week 24(Baseline, Week 24)
- Change From Baseline In NCC Concentrations Adjusted For Mo Plasma Concentration At Week 24(Baseline, Week 24)
- Time To Normalization Of NCC Adjusted For Mo Plasma Concentration In Participants With Elevated Baseline NCC(Up to last assessment (up to Week 176))
- Change From Baseline In Neurological Status Using The UWDRS (Neurological Subscore; Parts II, III, And Total Score) At Week 24(Baseline, Week 24)
- Change From Baseline In Psychiatric Status Dimension Using Mini International Neuropsychiatric Interview (M.I.N.I.) Tracking Standardized Scores At Week 24(Baseline, Week 24)
- QoL/PRO Assessed By The 8-Item Medication Adherence Scale (MMAS-8) At Week 24(Week 24)
- Change From Baseline In Quality Of Life (QoL)/Patient Reported Outcome (PRO) Assessed By The EQ-5D Descriptive System UK Health Index Scores At Week 24(Baseline, Week 24)
- QoL/PRO Assessed By The Treatment Satisfaction Questionnaire For Medication (TSQM-9) At Week 24(Week 24)
- Change From Baseline In Hepatic Laboratory Measure Bilirubin At Week 24(Baseline, Week 24)
- Change From Baseline In Exchangeable Cu At Week 24(Baseline, Week 24)
- Change From Baseline In Hepatic Laboratory Measure International Normalized Ratio (INR) At Week 24(Baseline, Week 24)
- Change From Baseline In Speciation Profiling (Mo, Cu, And Protein Complex Profiling Using Size Exclusion Chromatography) At Week 24(Baseline, Week 24)
- Change From Baseline In 24-Hour Urinary Mo And Cu At Week 24(Baseline, Week 24)
- Pharmacokinetics (PK): Area Under The Curve From Time 0 to 24 (AUC0-24) Of Plasma Total Mo(0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24)
- PK: Maximum Concentration (Cmax) Of Plasma Total Mo(0, 1, 2, 3, 4, 5, 6, 8, and 12 (10 to 12) hours post-dose on Day 1, Week 12, and Week 24)
- Extension Period: Change From Baseline In NCC Levels Adjusted For Mo Plasma Concentration(Baseline, last assessment (up to Week 176))