Chronic Kidney Disease-associated Pruritus
Conditions
Brief summary
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
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.
Interventions
DRUGMC2-25 cream
Topical application
DRUGMC2-25 vehicle
Topical application
Sponsors
MC2 Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Parallel-group, Randomized, Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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): 1. 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 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Weekly Mean Worst Itch Numeric Rating Score (WI-NRS) | 12 weeks | Mean change in 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. Weekly mean WI-NRS is calculated as the average of all and at least 4 non-missing WI-NRS values recorded in the subjects' diaries for the 7 days prior to and including the scheduled in clinic visits (8 days in total expected). The WI-NRS was scored on a 11-point numeric rating scale ranging from 0 to 10, where 0=no itch and 10=worst imaginable itch. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MC2-25 Cream MC2-25 cream Twice daily applications for 12 weeks
MC2-25 cream: Topical application | 73 |
| MC2-25 Vehicle MC2-25 vehicle Twice daily applications for 12 weeks
MC2-25 vehicle: Topical application | 38 |
| Total | 111 |
Baseline characteristics
| Characteristic | MC2-25 Cream | Total | MC2-25 Vehicle |
|---|---|---|---|
| Age, Continuous | 62.0 Years STANDARD_DEVIATION 15.13 | 63.7 Years STANDARD_DEVIATION 14.81 | 66.9 Years STANDARD_DEVIATION 13.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 73 Participants | 111 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 16 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 7 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 55 Participants | 86 Participants | 31 Participants |
| Region of Enrollment Germany | 10 participants | 16 participants | 6 participants |
| Region of Enrollment Hungary | 22 participants | 31 participants | 9 participants |
| Region of Enrollment Poland | 0 participants | 1 participants | 1 participants |
| Region of Enrollment United Kingdom | 41 participants | 63 participants | 22 participants |
| Sex: Female, Male Female | 37 Participants | 53 Participants | 16 Participants |
| Sex: Female, Male Male | 36 Participants | 58 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 73 | 1 / 37 |
| other Total, other adverse events | 4 / 73 | 2 / 37 |
| serious Total, serious adverse events | 11 / 73 | 6 / 37 |
Outcome results
Primary
Mean Change in Weekly Mean Worst Itch Numeric Rating Score (WI-NRS)
Mean change in 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. Weekly mean WI-NRS is calculated as the average of all and at least 4 non-missing WI-NRS values recorded in the subjects' diaries for the 7 days prior to and including the scheduled in clinic visits (8 days in total expected). The WI-NRS was scored on a 11-point numeric rating scale ranging from 0 to 10, where 0=no itch and 10=worst imaginable itch.
Time frame: 12 weeks
Population: The number (59/34) of participants in the full analysis set is the number of subjects with at least a baseline weekly mean WI-NRS score
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MC2-25 Cream | Mean Change in Weekly Mean Worst Itch Numeric Rating Score (WI-NRS) | -3.70 score on a scale | Standard Deviation 2.961 |
| MC2-25 Vehicle | Mean Change in Weekly Mean Worst Itch Numeric Rating Score (WI-NRS) | -3.87 score on a scale | Standard Deviation 2.203 |