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

Uremic Pruritus Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05885737
• Other study ID #: KOR-CHINA-301
• Secondary ID: JXHL2101166
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 30, 2023
• Est. completion date: July 2025

Study information

• Verified date: April 2024
• Source: Vifor Fresenius Medical Care Renal Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 260
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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)

Related Conditions & MeSH terms

• Pruritus
• Uremic Pruritus

Intervention

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 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Vifor Fresenius Medical Care Renal Pharma	Tigermed Consulting Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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