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)

Trial ID: 2022-500044-38-01
Protocol: MC2-25-C1 /ITCHINESS
Sponsor: Mc2 Therapeutics Limited

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendor

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 impacting their quality of life. The study aims to determine if the active treatment provides a meaningful reduction in pruritus symptoms compared to the vehicle.

The secondary objectives include exploring the **safety** of MC2-25 cream compared to the MC2-25 vehicle in the same patient population. Additionally, the study seeks to investigate the subclinical effects of MC2-25 cream in adults with CKD-aP. These objectives are crucial for understanding the overall benefit-risk profile of the treatment and its potential impact on underlying disease mechanisms.

Participants

The clinical trial involves a total of **60 participants** who are adults diagnosed 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 were selected based on their ability to understand the trial and willingness to comply with its requirements, as well as having provided written informed consent. The trial specifically targets individuals with chronic kidney disease stages G3-G5, with some participants undergoing haemodialysis or haemodiafiltration. Lifestyle considerations such as diet and physical activity are not specified, but participants must have at least moderate CKD-aP, 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 trial does not exclude vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across a broad demographic.

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 WI-NRS scores.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age, CKD stage, and pruritus severity. Eligible participants will provide written informed consent and undergo baseline assessments. Follow-up visits will occur at regular intervals to monitor safety, adherence, and efficacy outcomes. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the overall impact of the treatment.

The expected length of participant involvement is approximately 12 weeks, with conditions for early termination including non-compliance with trial requirements, adverse events, or withdrawal of consent. Participants must meet inclusion criteria, such as being adults with CKD stages G3-G5 and moderate CKD-aP, and must agree to use effective contraception if of childbearing potential. The trial is not a low-intervention study and is categorized as a Phase II clinical trial.

Treatment

The clinical trial involves the evaluation of **MC2-25 cream**, an experimental medication formulated as a cream for **cutaneous use**. The active substance in this formulation is **alanyl glutamine**, a protein-derived compound. The cream is administered topically with a maximum daily dose of 50 grams and a total maximum dose of 4200 grams over a 12-week treatment period. The product is manufactured by MC2 Therapeutics Ltd and is identified by the sponsor product code MC2-25. The trial aims to assess the efficacy and safety of this cream in subjects with chronic kidney disease-associated pruritus (CKD-aP).

In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is identical to the test product in all aspects except for the absence of the active substance, alanyl glutamine. The placebo is also administered topically in the same pharmaceutical form as the MC2-25 cream. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias in the assessment of the treatment's efficacy and safety.

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. These efficacy parameters will be collected and analyzed using patient-reported outcomes documented in diaries over the course of the trial. The trial aims to explore the clinical efficacy of the MC2-25 cream in adults with CKD-aP, with the primary objective of determining its effectiveness compared to the vehicle cream.

Inclusion and Exclusion Criteria

check_circle

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.

cancel

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 an uncontrolled Human Immunodeficiency Virus (HIV) or a known active generalized infection (bacterial, viral, or fungal) that, in the opinion of the investigator, may interfere with the assessment of safety or efficacy in this trial
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 of 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 of 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