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

Phase 3

Completed

• Conditions: Uremic Pruritus
• Interventions: Drug: Difelikefalin Injection; Drug: Placebo Injection

• Registration Number: NCT05885737
• Lead Sponsor: Vifor Fresenius Medical Care Renal Pharma

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.

Study Timeline

• Study First Submitted: 2023-05-17
• Study Start: 2023-05-30
• Study First Submitted QC: 2023-06-01
• Study First Posted: 2023-06-02
• Primary Completion: 2024-09-25
• Study Completion: 2024-09-25
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 184

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
12-weeks double-blind period - Difelikefalin	Difelikefalin Injection	-
12-weeks double-blind period - Placebo	Placebo Injection	-
14-weeks optional open-label period following the double-blind period - Difelikefalin	Difelikefalin Injection	-

Primary Outcome Measures

Name	Time	Method
Change from baseline in the weekly mean of the daily 24-hour WI-NRS score at Week 4 of the double-blind period	Week 4	The degree of the most intense itching within a day will be assessed using Worst Itch Numeric Rating Scale (WI-NRS) scores.

Secondary Outcome Measures

Name	Time	Method
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 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.	End of double-blind period, week 12	The 5-D itch scale is a questionnaire where patients assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution).
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.	End of double-blind period, week 12	The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity.
Patient Global Impression of Change.	End of double-blind period, week 12	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

Trial Locations

Locations (35)

Investigator Site 36; 🇨🇳 Nantong, China

Investigator Site 40; 🇨🇳 Shanghai, China

Investigator Site 01; 🇨🇳 Beijing, China

Investigator Site 18; 🇨🇳 Shenyang, China

Investigator Site 16; 🇨🇳 Shenzhen, China

Investigator Site 08; 🇨🇳 Shihezi, China

Investigator Site 32; 🇨🇳 Shijiazhuang, China

Investigator Site 17; 🇨🇳 Wuhan, China

Investigator Site 13; 🇨🇳 Xiamen, China

Investigator Site 04; 🇨🇳 Ürümqi, China

Investigator Site 25; 🇨🇳 Baotou, China

Investigator Site 12; 🇨🇳 Jiaxing, China

Investigator Site 34; 🇨🇳 Mianyang, China

Investigator Site 41; 🇨🇳 Shijiazhuang, China

Investigator Site 21; 🇨🇳 Shenyang, China

Investigator Site 20; 🇨🇳 Taiyuan, China

Investigator Site 15; 🇨🇳 Xianyang, China

Investigator Site 31; 🇨🇳 Zhenjiang, China

Investigator Site 26; 🇨🇳 Changsha, China

Investigator Site 07; 🇨🇳 Beijing, China

Investigator Site 06; 🇨🇳 Guangzhou, China

Investigator Site 02; 🇨🇳 Lanzhou, China

Investigator Site 19; 🇨🇳 Nanjing, China

Investigator Site 24; 🇨🇳 Taiyuan, China

Investigator Site 39; 🇨🇳 Tianjin, China

Investigator Site 33; 🇨🇳 Wuxi, China

Investigator Site 38; 🇨🇳 Xinxiang, China

Investigator Site 22; 🇨🇳 Xining, China

Investigator Site 11; 🇨🇳 Yangzhou, China

Investigator Site 23; 🇨🇳 Zhengzhou, China

Investigator Site 30; 🇨🇳 Yibin, China

Investigator Site 29; 🇨🇳 Yinchuan, China

Investigator Site 35; 🇨🇳 Zhuzhou, China

Investigator Site 10; 🇨🇳 Nanjing, China

Investigator Site 03; 🇨🇳 Nanjing, China