Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus

A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase 3, Clinical Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus

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.

Study Overview

• Status: Completed
• Conditions: Uremic Pruritus
• Intervention / Treatment: Drug: Difelikefalin Injection; Drug: Placebo Injection

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.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China
    • Investigator Site 25
  • Beijing, China
    • Investigator Site 01
  • Beijing, China
    • Investigator Site 07
  • Changsha, China
    • Investigator Site 26
  • Guangzhou, China
    • Investigator Site 06
  • Jiaxing, China
    • Investigator Site 12
  • Lanzhou, China
    • Investigator Site 02
  • Mianyang, China
    • Investigator Site 34
  • Nanjing, China
    • Investigator Site 03
  • Nanjing, China
    • Investigator Site 10
  • Nanjing, China
    • Investigator Site 19
  • Nantong, China
    • Investigator Site 36
  • Shanghai, China
    • Investigator Site 40
  • Shenyang, China
    • Investigator Site 18
  • Shenyang, China
    • Investigator Site 21
  • Shenzhen, China
    • Investigator Site 16
  • Shihezi, China
    • Investigator Site 08
  • Shijiazhuang, China
    • Investigator Site 32
  • Shijiazhuang, China
    • Investigator Site 41
  • Taiyuan, China
    • Investigator Site 20
  • Taiyuan, China
    • Investigator Site 24
  • Tianjin, China
    • Investigator Site 39
  • Wuhan, China
    • Investigator Site 17
  • Wuxi, China
    • Investigator Site 33
  • Xiamen, China
    • Investigator Site 13
  • Xianyang, China
    • Investigator Site 15
  • Xining, China
    • Investigator Site 22
  • Xinxiang, China
    • Investigator Site 38
  • Yangzhou, China
    • Investigator Site 11
  • Yibin, China
    • Investigator Site 30
  • Yinchuan, China
    • Investigator Site 29
  • Zhengzhou, China
    • Investigator Site 23
  • Zhenjiang, China
    • Investigator Site 31
  • Zhuzhou, China
    • Investigator Site 35
  • Ürümqi, China
    • Investigator Site 04

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12-weeks double-blind period - Difelikefalin	Drug: Difelikefalin Injection; Participants receive Difelikefalin three times a week (0.5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.
Placebo Comparator: 12-weeks double-blind period - Placebo	Drug: Placebo Injection; Participants receive Placebo three times a week (0.5 micrograms/kg dry body weight). Placebo is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.
Experimental: 14-weeks optional open-label period following the double-blind period - Difelikefalin	Drug: Difelikefalin Injection; Participants receive Difelikefalin three times a week (0.5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Weekly Mean of the Daily 24-hour WI-NRS Score at Week 4 of the DB Period	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.	From Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a 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. Missing weekly mean WI-NRS data were imputed using missing at random (MAR) multiple imputation (MI) approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data. The percentage of participants were estimated using a logistic regression model with terms for treatment group, baseline WI-NRS score, use of anti-itch medication during the week prior to randomisation, and the presence of specific medical conditions at baseline.	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	On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a 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. Missing weekly mean WI-NRS data were imputed using MAR-MI approach, assuming that participants who do not have weekly mean WI-NRS score at a timepoint would have similar weekly mean WI-NRS scores as other participants in their respective treatment arm who have complete data.	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	On a daily basis, participants recorded the intensity of the worst itching they experienced over the past 24 hours using a 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 was calculated for the analysis. The weekly mean of the daily values of the daily 24-hour WI-NRS was calculated for the analysis. 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.	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)	The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects.	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)	The 5-D itch scale is a questionnaire where participants assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). The scores of each of the 5 domains are achieved separately and then summed together to obtain a total 5-D score. 5-D itch scale scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus) where a higher score indicates a more severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the 5-D itch scale total score was estimated using the MMRM method. The MMRM model included use of prior anti-itch medication (yes/no), presence of specific medical conditions at baseline (yes/no), treatment sequence, visit, and treatment sequence-by-visit-interaction as fixed categorical effects and baseline 5-D Itch score (total score) as fixed continuous effects.	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)	The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the 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 skindex-10 scale score (total score) as fixed continuous effects.	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)	The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. Participants are asked the question "During the past week, how often have you been bothered by" and respond by filling in 1 of 7 circles numbered from 0 (labelled with the anchor phrase "never bothered") to 6 (labelled as "always bothered") for each of the 10 questions. The total score is the sum of the numeric value of each answered question. Here, a higher score indicated a severe outcome. The LS means of change from baseline in itch-related QoL as assessed by the Skindex-10 scale total score was estimated using the 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 skindex-10 scale score (total score) as fixed continuous effects.	From Baseline to OLE Period - Weeks 4, 8, 12, and 14
Patient Global Impression of Change	The Patient Global Impression of Change is a global participant reported outcome measure that assesses the change in itch (no change, improvement or worsening) overall relative to the start of the study. The scale has only 1 item, and the participant was asked to mark the category that best describes the change in itch ranging from "Very Much Improved" to "Very Much Worse". Number of participants within all individual categories are reported here.	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)

Collaborators and Investigators

• Sponsor: Vifor Fresenius Medical Care Renal Pharma
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Study Director: Milica Enoiu, PhD, Vifor Pharma Group

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2023
• Primary Completion (Actual): September 25, 2024
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Difelikefalin; Uremic Pruritus; CKD-aP; Chronic kidney disease-associated pruritus
• Additional Relevant MeSH Terms: Skin Manifestations; Skin Diseases; Pruritus; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; difelikefalin
• Other Study ID Numbers: KOR-CHINA-301; CTR20220844 (Other Identifier: China CTR Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country-specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No