The MC2-25 Cream in Subjects wITh CHronic KIdNEy Disease-aSsociated prurituS (ITCHINESS) Trial

Study Overview
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Brief Summary
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The purpose of this study is to access the efficacy and safety of MC2-25 cream and MC2-25 vehicle for treatment of chronic kidney disease associated pruritus (CKD)-aP).

Detailed Description
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In this trial, subjects who fulfil all inclusion and exclusion criteria are enrolled. Eligible subjects will be randomised in a 2:1 ratio to MC2-25 cream or MC2-25 vehicle, respectively. The subjects will apply the assigned investigational medicinal product (IMP) twice daily for 12 weeks.

Official Title
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A Parallel-group (2-Arm), Randomized, Double-blind, 12-week Trial to Evaluate the Efficacy and Safety of MC2-25 Cream and MC2-25 Vehicle in Subjects With Chronic Kidney Disease-associated Pruritus (CKD-aP)

Conditions
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Chronic Kidney Disease-associated Pruritus

Intervention / Treatment
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* Drug: MC2-25 cream
* Drug: MC2-25 vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or non-pregnant females of any race or ethnicity who are ≥ 18 years of age at the time of screening Has provided written informed consent Chronic (>3 months) kidney disease (CKD) stages G3-G5 (i.e., estimated glomerular filtration rate [eGFR] by CKD-EPI creatinine 2021 equation <60 mL/min/1.73 m2) Specifically for CKD subjects on haemodialysis (HD) or haemodiafiltration (HDF): Subjects must be established on HD or HDF 3 times per week continuously for at least 3 months prior to the start of screening and must not have plans to change from HD to HDF or vice versa during the trial Subjects who require an occasional additional HD or HDF treatment to manage fluid overload may be enrolled as long as it is anticipated that no more than 4 such treatments will be required in any given month At least moderate CKD-aP defined as WI-NRS ≥4 Female subjects must be of either: a. Non-childbearing potential or b. Childbearing potential Exclusion Criteria: Has a functioning kidney transplant or is scheduled to receive a kidney transplant during the trial (Note: subject can be on waiting list for kidney transplant) Subjects who receive peritoneal dialysis In the opinion of the investigator has pruritus attributed to a cause other than CKD or its complications Has localized itch restricted to the palms of the hands Has concurrent skin conditions (including but not limited to pruritic dermatoses, active skin infections, ulcerations) that may limit or prevent application of MC2-25 cream or MC2-25 vehicle or that may interfere with evaluation of the effects of MC2-25 cream or MC2-25 vehicle on the skin at the Screening or Baseline visits Subjects who will have skin biopsies performed must not have any known hypersensitivity to the local anaesthetic or diagnosed bleeding disorders Has a concurrent or recent (within 12 months prior to screening) medical condition that, in the opinion of the investigator, could pose undue risk to the subject, impede completion of the trial procedures, or would compromise the validity of the trial measurements Has a known current generalized infection (bacterial, viral, or fungal) Start of a new or change to existing systemic treatment for CKD-aP Use of emollients on CKD-aP areas within 10 days prior to the Baseline visit Use of any topical treatment on CKD-aP areas Use of any light therapy for CKD-aP Use of non-biologic systemic immunosuppressive treatment Use of biologic systemic treatment Subjects not currently on dialysis but who are likely to initiate routine dialysis during participation in the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel-group, Randomized, Double-blind
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MC2-25 cream<br>MC2-25 cream Twice daily applications for 12 weeks | Drug: MC2-25 cream<br>* Topical application<br>|
| Placebo Comparator: MC2-25 vehicle<br>MC2-25 vehicle Twice daily applications for 12 weeks | Drug: MC2-25 vehicle<br>* Topical application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in weekly mean Worst Itch Numeric Rating Score (WI-NRS) | Mean change in weekly WI-NRS score, calculated as the average of weekly means WI-NRS values from Baseline to Week 12 for MC2-25 cream compared to MC2-25 vehicle. | 12 weeks |