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: Active, not recruiting
• 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 Contact: Name: KOR-CHINA-301 Clinical Study Team; Phone Number: +41 58 851 80 00; Email: clinicaltrials@cslbehring.com

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 double-blind period	The degree of the most intense itching within a day will be assessed using Worst Itch Numeric Rating Scale (WI-NRS) scores.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 4 of double-blind period
Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 8 of double-blind period
Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 12 of double-blind period
Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 4 of double-blind period
Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 8 of double-blind period
Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS		Week 12 of double-blind period
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.	The 5-D itch scale is a questionnaire where patients assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution).	End of double-blind period, week 12
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.	The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity.	End of double-blind period, week 12
Patient Global Impression of Change.	The Patient Global Impression of Change is a questionnaire that assesses the change in itch compared to the itch at the start of the study	End of double-blind period, week 12

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 30, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

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 (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Difelikefalin; Uremic Pruritus; CKD-aP; Chronic kidney disease-associated pruritus
• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus
• Other Study ID Numbers: KOR-CHINA-301; JXHL2101166 (Other Identifier: Center for Drug Evaluation (CDE), China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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