A Study to Test How Well Alanyl Glutamine Cream Works and How Safe It Is for Adults with Itching Caused by Chronic Kidney Disease

Trial ID: 2022-500044-38-00
Protocol: MC2-25-C1 /ITCHINESS
Sponsor: Mc2 Therapeutics Limited

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Diseases & Conditions

Chronic kidney disease-associated pruritus

Objectives

The primary objective of this study is to evaluate the **clinical efficacy** of MC2-25 cream compared to the MC2-25 vehicle in adults with **Chronic Kidney Disease-associated Pruritus (CKD-aP)**. This is clinically relevant as CKD-aP is a common and distressing symptom in patients with chronic kidney disease, significantly affecting their quality of life. Understanding the efficacy of MC2-25 cream could provide a new therapeutic option for managing this condition.

The secondary objectives are to explore the **safety** of MC2-25 cream compared to the MC2-25 vehicle in adults with CKD-aP and to investigate the subclinical effects of MC2-25 cream in this population. These objectives are important for ensuring the comprehensive assessment of the treatment's risk-benefit profile and understanding its broader impact on the condition.

Participants

The clinical trial involves a total of **60 participants** who are adults with **Chronic Kidney Disease associated Pruritus** (CKD-aP). The study population includes both male and female subjects, aged 18 years and older, encompassing a diverse range of races and ethnicities. Participants are required to have chronic kidney disease stages G3-G5, with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m². The trial specifically includes individuals undergoing haemodialysis or haemodiafiltration, who have been on a stable treatment regimen for at least three months prior to screening. Participants must exhibit at least moderate CKD-aP, as defined by a WI-NRS score of 4 or greater. Female participants of childbearing potential are required to use highly effective contraception methods during the trial. The selection process ensures that participants are capable of understanding the trial and willing to comply with its requirements, having provided written informed consent. The trial does not exclude vulnerable populations, allowing for a comprehensive assessment of the treatment's efficacy across a representative sample of the affected population.

Plans and Procedures

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of MC2-25 cream compared to a placebo in subjects with **chronic kidney disease-associated pruritus** (CKD-aP). The trial will span a duration of 12 weeks, during which participants will be randomly assigned to receive either the active treatment or the placebo. The primary objective is to assess the clinical efficacy of MC2-25 cream in reducing pruritus symptoms, as measured by the weekly mean WI-NRS score from baseline to week 12. Secondary endpoints include the percentage of subjects achieving significant improvements in their pruritus scores.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, CKD stage, and pruritus severity. Following successful screening, participants will be enrolled and randomized into one of the two study arms. Throughout the trial, follow-up visits will be conducted to monitor safety, adherence, and efficacy outcomes. The end-of-study visit will occur at the conclusion of the 12-week treatment period, where final assessments will be made.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with study protocols, adverse events, or withdrawal of consent. Participants are required to adhere to the study regimen and attend all scheduled visits to ensure the integrity of the trial data. The trial is conducted in accordance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants.

Treatment

The clinical trial involves the use of **MC2-25 cream**, an experimental medication formulated as a cream for **cutaneous use**. The active substance in MC2-25 cream is **alanyl glutamine**. The maximum daily dose is 50 grams, with a total maximum dose of 4200 grams over a treatment period of 12 weeks. The cream is applied topically, and the administration schedule is designed to ensure consistent dosing throughout the trial duration. Participant compliance will be monitored through regular assessments and documentation of application adherence.

The study also includes a **placebo** treatment, which is identical to the MC2-25 cream in all aspects except for the absence of the active substance, alanyl glutamine. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered in the same manner as the MC2-25 cream, with the same dosing schedule and compliance monitoring procedures.

Efficacy

The efficacy of MC2-25 cream in treating **chronic kidney disease-associated pruritus (CKD-aP)** will be assessed through a randomized, double-blind, 12-week clinical trial. The primary endpoint for evaluating efficacy is the mean change in the weekly mean Worst Itch Numeric Rating Scale (WI-NRS) recorded in the subject's diary from Baseline to Week 12, comparing MC2-25 cream to the MC2-25 vehicle. Secondary endpoints include the percentage of subjects achieving a ≥4-point improvement, a ≥3-point improvement, and a complete response in the weekly mean WI-NRS from Baseline to Week 12.

Data collection will involve patient-reported outcomes using the WI-NRS, a validated scale for measuring itch severity. Subjects will record their itch severity daily in a diary, and these scores will be averaged weekly. The analysis will focus on comparing the changes in these scores between the treatment and placebo groups over the 12-week period. The trial aims to provide robust data on the efficacy of MC2-25 cream in reducing pruritus symptoms in patients with CKD-aP.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Adult males or non-pregnant females of any race or ethnicity who are equal/older 18 years of age at the time of screening
Able to understand the trial and willing to comply with trial requirements
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): a.) Subjects must be established on HD or HDF 3 times per week continuously for at least 3 months prior to the start of screening (Note: at least the 2 last weeks of the 3-month period must have been in-center dialysis) and must not have plans to change from HD to HDF or vice versa during the trial. b.)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 equal/greater 4 (i.e., the average of all and at least 4 non-missing scores reported by the subject in the diary for 7 days prior to and including the Baseline day, 8 days in total)
Female subjects must be of either: • Non-childbearing potential, i.e., postmenopausal* or confirmed sterile (e.g., hysterectomy, bilateral salpingectomy or bilateral oophorectomy). (*Note: a postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient) or, • Childbearing potential with a negative highly sensitive urine pregnancy test at the Baseline visit or (in the case of anuria) a negative serum pregnancy test at the Baseline visit that is no more than 3 days old.
Female subjects of childbearing potential must agree to use a highly effective method of contraception (i.e., a method with a failure rate of less than 1% per year when used consistently and correctly) while receiving double-blind treatment.

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Exclusion Criteria

In the opinion of the investigator, the subject is unlikely to comply with the clinical trial protocol.
Has a functioning kidney transplant or is scheduled to receive a kidney transplant during the trial
Subjects who receive peritoneal dialysis
In the opinion of the investigator has pruritus attributed to a cause other than CKD or its complications, including but not limited to dermatological disease (e.g., atopic dermatitis, psoriasis) or liver disease (cholestatic pruritus)
Has localized itch restricted to the palms of the hands
Only has pruritus during haemodialysis sessions
Has concurrent skin conditions 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. Note: subjects with suspected uremic platelet dysfunction, without other bleeding diatheses, can be enrolled if the investigator agrees.
Known history of allergic reaction to any ingredients in MC2-25 cream or MC2-25 vehicle
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)
Is pregnant, breast feeding, or planning a pregnancy
Start of a new or change to existing systemic treatment for CKD-aP within 21 days prior to the Baseline visit
Use of emollients on CKD-aP areas within 10 days prior to the Baseline visit
Use of any topical treatment on CKD-aP areas, including but not limited to antihistamines, or corticosteroids within 21 days prior to the Baseline visit
Use of any light therapy for CKD-aP within 35 days prior to the Baseline visit
Start of a new or change to existing non-biologic systemic immunosuppressive treatment, including but not limited to corticosteroids, cyclosporin, and tacrolimus 21 days prior to the Baseline visit.
Start of a new or change to existing biologic systemic treatment, including but not limited to etanercept, adalimumab, alefacept, infliximab, and ustekinumab within 3 months or 5 half-lives (whichever is longer) prior to the Baseline visit
Subjects who consent to having skin biopsies performed who are using anticoagulation treatment and are judged by the investigator to have an unacceptable risk of excessive bleeding in association with the skin biopsy
Subjects not currently on dialysis but who are likely to initiate routine dialysis during participation in the trial
Received another investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening or is planning to participate in another clinical trial while enrolled in this trial
Previously randomized in this trial