A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase 3, Clinical Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 260
- 试验地点
- 35
- 主要终点
- Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period
研究概览
简要总结
This a multicentre study that consists of a 12-week double-blind period, and an optional 14-week open-label extension period and a 1-week follow-up period.
详细描述
Total study duration for a single subject is 31 to 32 weeks with a 4-week screening period, a 12-week double-blind period, a 14-week optional open-label extension period, and a 1-week follow-up period. For subjects not participating in the open-label extension period, the total study duration is 17 weeks.
Difelikefalin will be administered in the double-blind and open-label period 3 times a week at the end of each dialysis session. The total dose of the investigational product will be determined based on the subject's prescription dry body weight.
The primary objective of the study is:
To evaluate the efficacy of difelikefalin 0.5 μg/kg compared to placebo in reducing the intensity of itch in HD Chinese subjects with moderate-to-severe pruritus.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with chronic kidney disease (CKD) on HD 3 times weekly for ≥12 weeks prior to the informed consent procedure (including the date of informed consent) who can continue HD without changing its frequency or method.
- •If female, is not pregnant, or nursing.
- •If female:
- •Is surgically sterile; or
- •Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or
- •Has a negative serum pregnancy test within 7 days before first dose of investigational product and agrees to use acceptable contraceptive measures (e.g., hormonal contraceptives, barrier with spermicide, intrauterine device, vasectomised partner, or abstinence) from the time of informed consent until 7 days after the last dose of investigational product.
- •If male, agrees not to donate sperm after the first dose of investigational product administration until 7 days after the last dose of investigational product, and agrees to use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of investigational product.
- •Subjects with a prescription dry body weight between 40 and 100 kg, inclusive.
排除标准
- •Planned or anticipated to receive a kidney transplant during the study.
- •Has localised itch restricted to the palms of the hands.
- •Has pruritus only during the dialysis session
- •Subjects with severe hepatic impairment (Child-Pugh Class C) or concurrent hepatic cirrhosis.
- •Subject is receiving ongoing ultraviolet B treatment and anticipates receiving such treatment during the study.
- •Significant systolic or diastolic heart failure (e.g., New York Heart Association Class IV congestive heart failure)
- •Subjects with concurrent malignancy except excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ that has been excised or resected completely.
- •Known or suspected history of alcohol, narcotic, or other drug abuse, or substance dependence within 12 months prior to screening.
- •Severe mental illness or cognitive impairment (e.g., dementia) or other concurrent mental disorder that, in the opinion of the Investigator, would compromise the validity of study measurements.
- •Any other relevant acute or chronic medical or neuropsychiatric condition within 3 months prior to screening (e.g., diagnosis of encephalopathy, coma, delirium).
- •New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening.
- •New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening.
- •Subject is receiving prohibited medication (e.g., nalfurafine hydrochloride, opioid antagonists)
研究组 & 干预措施
12-weeks double-blind period - Difelikefalin
干预措施: Difelikefalin Injection (Drug)
12-weeks double-blind period - Placebo
干预措施: Placebo Injection (Drug)
14-weeks optional open-label period following the double-blind period - Difelikefalin
干预措施: Difelikefalin Injection (Drug)
结局指标
主要结局
Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period
时间窗: From Baseline to Week 4
On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a numerical rating scale (NRS) scale from 0 to 10, where 0 represents "no itching" and 10 was "worst itching imaginable". A higher score indicated a more severe outcome. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. The least square (LS) means of change from baseline to Week 4 in the weekly mean of the daily 24-hour WI-NRS score was estimated using the mixed model repeated measures (MMRM) method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment, visit, and treatment-by-visit-interaction as fixed categorical effects and baseline WI-NRS score as fixed continuous effects.
次要结局
- Percentage of Participants Achieving Greater Than or Equal to (>=) 3-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period(From Baseline, and at Weeks 4, 8, and 12)
- Percentage of Participants Achieving at Least 4-point Improvement From Baseline With Respect to the Weekly Mean of the Daily 24-hour WI-NRS in the DB Period(From Baseline, and at Weeks 4, 8, and 12)
- Change From Baseline in the Weekly Mean of the 24-hour WI-NRS Score at Each Week of the DB Period(From Baseline to Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12)
- Change From Baseline in Itch-related Quality-of-life (QoL) as Assessed by the 5-D Itch Scale Total Score (DB Period)(From Baseline to Weeks 4, 8, and 12)
- Change From Baseline in Itch-related QoL as Assessed by the 5-D Itch Scale Total Score (OLE Period)(From Baseline to OLE Period - Weeks 4, 8, 12, and 14)
- Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (DB Period)(From Baseline to Weeks 4, 8, and 12)
- Change From Baseline in Itch-related QoL as Assessed by the Skindex-10 Scale Total Score (OLE Period)(From Baseline to OLE Period - Weeks 4, 8, 12, and 14)
- Patient Global Impression of Change(At Week 12)
- Number of Participants With Adverse Events (AEs)(Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up))
- Number of Participants With Clinically Significant Abnormal 12-lead Electrocardiogram (ECG)(Up to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up))
- Number of Participants With Clinically Relevant Change From Baseline in Vital Signs and Laboratory Evaluations(From baseline to Week 27 (12 weeks in DB + 14 weeks in OLE +1 week of follow up))