Clinical trial NCT05885737: Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus
Official title: A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase 3, Clinical Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uremic Pruritus
Keywords: Uremic Pruritus
Chronic kidney disease-associated pruritus
CKD-aP
Difelikefalin
Lead sponsor: Vifor Fresenius Medical Care Renal Pharma
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2023-06-02
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Is surgically sterile; or
  2. Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or
  3. 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.

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Change from baseline in the weekly mean of the daily 24-hour WI-NRS score at Week 4 of the double-blind period
timeFrame: Week 4
Secondary outcomes:
measure: Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 4 of double-blind period
measure: Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 8 of double-blind period
measure: Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 12 of double-blind period
measure: Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 4 of double-blind period
measure: Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 8 of double-blind period
measure: Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS
timeFrame: Week 12 of double-blind period
measure: Change from baseline in itch-related Quality of Life (QoL) at the end of Week 12 of the double-blind period, as assessed by the 5-D itch scale total score.
timeFrame: End of double-blind period, week 12
measure: Change from baseline in itch-related QoL at the end of Week 12 of the double-blind period, as assessed by the Skindex-10 scale total score.
timeFrame: End of double-blind period, week 12
measure: Patient Global Impression of Change.
timeFrame: End of double-blind period, week 12
Other outcomes:
Locations:
city: Baotou
country: China
facility: Investigator Site 25
city: Beijing
country: China
facility: Investigator Site 01
city: Beijing
country: China
facility: Investigator Site 07
city: Changsha
country: China
facility: Investigator Site 26
city: Guangzhou
country: China
facility: Investigator Site 06
city: Jiaxing
country: China
facility: Investigator Site 12
city: Lanzhou
country: China
facility: Investigator Site 02
city: Mianyang
country: China
facility: Investigator Site 34
city: Nanjing
country: China
facility: Investigator Site 03
city: Nanjing
country: China
facility: Investigator Site 10
city: Nanjing
country: China
facility: Investigator Site 19
city: Nantong
country: China
facility: Investigator Site 36
city: Shanghai
country: China
facility: Investigator Site 40
city: Shenyang
country: China
facility: Investigator Site 18
city: Shenyang
country: China
facility: Investigator Site 21
city: Shenzhen
country: China
facility: Investigator Site 16
city: Shihezi
country: China
facility: Investigator Site 08
city: Shijiazhuang
country: China
facility: Investigator Site 32
city: Shijiazhuang
country: China
facility: Investigator Site 41
city: Taiyuan
country: China
facility: Investigator Site 20
city: Taiyuan
country: China
facility: Investigator Site 24
city: Tianjin
country: China
facility: Investigator Site 39
city: Wuhan
country: China
facility: Investigator Site 17
city: Wuxi
country: China
facility: Investigator Site 33
city: Xiamen
country: China
facility: Investigator Site 13
city: Xianyang
country: China
facility: Investigator Site 15
city: Xining
country: China
facility: Investigator Site 22
city: Xinxiang
country: China
facility: Investigator Site 38
city: Yangzhou
country: China
facility: Investigator Site 11
city: Yibin
country: China
facility: Investigator Site 30
city: Yinchuan
country: China
facility: Investigator Site 29
city: Zhengzhou
country: China
facility: Investigator Site 23
city: Zhenjiang
country: China
facility: Investigator Site 31
city: Zhuzhou
country: China
facility: Investigator Site 35
city: Ürümqi
country: China
facility: Investigator Site 04
Study officials:
affiliation: Vifor Pharma Group
name: Milica Enoiu, PhD
role: STUDY_DIRECTOR
References: