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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mc2 Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2022-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MC2 Therapeutics Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is to explore the clinical efficacy of MC2-25 cream compared to MC2-25 vehicle in adults with chronic kidney disease-associated pruritus (CKD-aP).

Secondary objectives 1

1. The secondary objectives are to explore the safety of MC2-25 cream compared to MC2-25 vehicle in adults with CKD-aP and other objectives are to explore the subclinical effects of MC2-25 cream in adults with CKD-aP.

Conditions and MedDRA coding

Chronic Kidney Disease associated Pruritus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Adult males or non-pregnant females of any race or ethnicity who are equal/older 18 years of age at the time of screening
2. Able to understand the trial and willing to comply with trial requirements
3. Has provided written informed consent
4. 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)
5. 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.
6. 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)
7. 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.
8. 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.

Exclusion criteria 22

1. In the opinion of the investigator, the subject is unlikely to comply with the clinical trial protocol.
2. Has a functioning kidney transplant or is scheduled to receive a kidney transplant during the trial
3. Subjects who receive peritoneal dialysis
4. 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)
5. Has localized itch restricted to the palms of the hands
6. Only has pruritus during haemodialysis sessions
7. 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
8. 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.
9. Known history of allergic reaction to any ingredients in MC2-25 cream or MC2-25 vehicle
10. 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.
11. Has a known current generalized infection (bacterial, viral, or fungal)
12. Is pregnant, breast feeding, or planning a pregnancy
13. Start of a new or change to existing systemic treatment for CKD-aP within 21 days prior to the Baseline visit
14. Use of emollients on CKD-aP areas within 10 days prior to the Baseline visit
15. 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
16. Use of any light therapy for CKD-aP within 35 days prior to the Baseline visit
17. 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.
18. 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
19. 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
20. Subjects not currently on dialysis but who are likely to initiate routine dialysis during participation in the trial
21. 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
22. Previously randomized in this trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in weakly mean WI-NRS recorded in the subject’s diary from Baseline to Week 12 for MC2-25 cream compared to MC2-25 vehicle.

Secondary endpoints 3

1. Percentage of subjects obtaining a ≥4-point improvement in weekly mean WI-NRS recorded in the subject’s diary from Baseline to Week 12 for MC2-25 cream compared to MC2-25 vehicle.
2. Percentage of subjects obtaining a ≥3-point improvement in weekly mean WI-NRS recorded in the subject’s diary from Baseline to Week 12 for MC2-25 cream compared to MC2-25 vehicle.
3. Percentage of subjects obtaining a complete response in weekly mean WI-NRS recorded in the subject’s diary from Baseline to Week 12 for MC2-25 cream compared to MC2-25 vehicle.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mc2 Therapeutics Limited

Sponsor organisation

Mc2 Therapeutics Limited

Address

1a Guildford Business Park

City

Guildford

Postcode

GU2 8XG

Country

United Kingdom

Scientific contact point

Organisation

Mc2 Therapeutics Limited

Contact name

Rikke Pordel Vind

Public contact point

Organisation

Mc2 Therapeutics Limited

Contact name

Rikke Pordel Vind

Third parties 1

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications