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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: ALXN1840 (Drug)
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.
干预措施: SoC Therapy (Drug)
结局指标
主要结局
Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
时间窗: Baseline to Week 48
dNCC is the directly quantified copper not bound to ceruloplasmin, obtained by inductively coupled plasma mass spectrometry after immunocapture and removal of ceruloplasmin. Baseline was defined as last non-missing value on or before first study drug administration. Least square (LS) mean and standard error (SE) was calculated using analysis of covariance (ANCOVA).
次要结局
- Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48(Baseline, Week 48)
- Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48(Baseline, Week 48)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Baseline up to Week 48)
- Change From Baseline in UWDRS Part III Total Score at Week 48(Baseline, Week 48)
- Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48(Baseline, Week 48)
- cNCC/cNCCcorrected Responder at Week 48(Week 48)
- Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48(Baseline, Week 48)
- Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48(Baseline, Week 48)
- Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48(Baseline, Week 48)
- Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48(Baseline, Week 48)
- Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48(Week 48)