A Phase III Clinical Study of MR13A9 in Hemodialysis Patients With Pruritus.

A Phase III Clinical Study of MR13A9 in Hemodialysis Patients With Pruritus

Double-blind, Placebo-controlled study to confirm the superiority of MR13A9 to placebo, and followed by extension, open-label treatment to confirm long-term safety of MA13A9 in hemodialysis patients with pruritus.

Study Overview

• Status: Completed
• Conditions: Uremic Pruritus
• Intervention / Treatment: Drug: MR13A9; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Multiple Locations, Japan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with Chronic Kidney Disease (CKD) has been on hemodialysis 3 times per week
• Patient receiving treatment for itch
• Patient has a baseline NRS score > 4

Exclusion Criteria:

• Patient has pruritus cause other than CKD or its complications
• Patients has hepatic cirrhosis
• Patient has a known history of allergic reaction to opiates

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MR13A9/MR13A9; Patients are administered MR13A9 for 6 weeks (double-blind period), followed by MR13A9 for 52 weeks (open-label period).	Drug: MR13A9; Intravenous administration
Placebo Comparator: Placebo/MR13A9; Patients are administered Placebo for 6 weeks (double-blind period), followed by MR13A9 for 52 weeks (open-label period).	Drug: MR13A9; Intravenous administration; Drug: Placebo; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Mean NRS Score at Week 4	The change from baseline in the mean NRS score at each time point was calculated using an MMRM with the change from baseline in the mean NRS score at each time point as an objective variable, group, time point, and group-by-time point interaction as fixed effects, mean NRS score at baseline and presence or absence of prior treatment with nalfurafine hydrochloride as dynamic allocation factors as a covariate, and subjects as a random effect for data up to Week 4 of the double-blind period in FAS. Looking back on the period between the time of awakening on the previous day of assessment and the time of awakening on the day of assessment (including sleeping hours) once daily, subjects will assess the NRS score for the most severe itching by themselves. The most severe itching within the day will be assessed in integer on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in mean itch NRS score	The most severe itching within the day will be recorded in integers on a scale ranging from 0 to 10, where 0 represents no itching and 10 represents worst itching imaginable.	Up to 58 weeks
Change from baseline in mean itch scores based on the Shiratori severity criteria	The symptoms during the day and the night will be recorded on a scale ranging from 0 to 4, where 0 represents no symptoms and 4 represents severe itching.	Up to 58 weeks
Percentage of subjects with 3-point improvement in mean itch NRS score	Percentage of subjects with 3-point improvement whose change from baseline in mean itch NRS score is ≤ -3	Up to 58 weeks
Percentage of subjects with 4-point improvement in mean itch NRS score	Percentage of subjects with 4-point improvement whose change from baseline in mean itch NRS score is ≤ -4	Up to 58 weeks
Change from baseline in Skindex-16 score	The frequency of bothered by itching will be recorded based on scale ranging from 0 to 6, where 0 represents never bothered and 6 represents always bothered.	Week 4, 10, 18, 26, 34, 46, 58
Change from baseline in 5-D itch scale score	Five components of condition of itching (duration, degree, direction, disability, distribution) will be recorded based on scale ranging from 5 to 25, with higher scores indicating worse itch-related QOL.	Week 4, 10, 18, 26, 34, 46, 58
Percentage of subjects with global symptoms in Patient Global Impression of Change (PGIC)	Subjects will record the overall symptom of itching from the screening period based on a 7-level scale consisting of very much improved, much improved, minimally improved, no change, minimally worsened, much worsened, and very much worsened.	Week 4, 10, 18, 26, 34, 46, 58

Collaborators and Investigators

• Sponsor: Kissei Pharmaceutical Co., Ltd.
• Investigators: Study Director: Yoshitaka Shimizu, Kissei Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Narita I, Tsubakihara Y, Takahashi N, Ebata T, Uchiyama T, Marumo M, Okamura S, Gejyo F; MR13A9-5 Trial Investigators. Difelikefalin for Hemodialysis Patients with Pruritus in Japan. NEJM Evid. 2023 Nov;2(11):EVIDoa2300094. doi: 10.1056/EVIDoa2300094. Epub 2023 Oct 17.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2021
• Primary Completion (Actual): January 25, 2022
• Study Completion (Actual): September 26, 2022

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: August 21, 2025
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Manifestations; Pruritus; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: MR13A9-5

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