Study Designed to Evaluate Safety and Efficacy of 1% Topical Formulation of KM-001 on Type 1 Punctate Palmoplantar Keratoderma or Pachyonychia Congenita Diseases

• Status: Recruiting
• Trial end date: 2024-12-30
• Target enrollment: 0
• Participant gender: All

Summary

In this phase 1 open label study for patients with type I punctate palmoplantar keratoderma or pachyonychia congenital, 2 arms will be recruited to be treated twice daily, with 1% topical KM-001.

Arm 1: up to 10 eligible patients will be treated for 12 weeks. Arm 2: up to 8 eligible patients will be treated for 16 weeks.

Treatment safety and efficacy will be assessed in the clinic visits (for arm 1 up to day 91, for arm 2 up to day 126). In between safety will also be assessed by phone visits.

At the in-clinic visits, treatment efficacy (lesion clearance - IGA, CGI-S, PGI-C, PGI-S and VAS pain) will also be assessed.

PK blood samples will be collected for arm 1: on Days 0, 7, 84 (EoT visit). One week after the end of treatment (EoT) visit, patients will return to the clinic for final safety, efficacy and PK evaluations. For arm 2, PK blood samples will be collected on days 0, 7, 84, 112 (EoT visit). Two weeks after the end of treatment (EoT) visit, patients will return to the clinic for final safety, efficacy and PK evaluations.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Kamari Pharma Ltd

Criteria

Inclusion Criteria:

1. Read, understood and signed an informed consent form (ICF) before any investigational procedure(s) are performed.

2. Male or female and aged 18 - 75 years at the time of screening

3. Clinical diagnosis of:

punctate keratoderma type I disease with confirmed heterozygous mutation in AAGAB gene OR pachyonychia congenita with confirmed heterozygous mutation in either KRT16, KRT17, KRT6A, KRT6B or KRT6C mutations.

4. The target treatment region is 0.5%-4% body surface area (BSA) including target lesions

5. CGI-S score of ≥2 (as assessed by the PI at screening).

6. Female patients of childbearing potential must agree to use a highly effective and approved method of contraception throughout the study and for 4 weeks after the last study drug administration. Male patients: female partners of male patients must use a reliable method of contraception during this study, and for 12 weeks after the last dose of study medications.

7. Female patients must refrain from donating eggs throughout the study and for 4 weeks after the last study drug administration. Male patients must refrain from sperm donation throughout the study and for 12 weeks after the last study drug administration.

8. Female patients of non-childbearing potential must meet one of the following criteria:

• Absence of menstrual bleeding for 1 year prior to screening without any other medical reason.

• Documented hysterectomy or bilateral oophorectomy at least 3 months before the study.

9. Patient is willing and able to comply with all time commitments and procedural requirements of the clinical study protocol.

Exclusion Criteria:

1. Known hypersensitivity or any suspected cross-allergy to the active pharmaceutical ingredient and/or excipients.

2. Regular alcohol consumption for males >21 units per week and for females >14 units per week (1 unit = 8gr of alcohol; e.g., 200 mL of 5% beer, 25 mL of 40% spirits or 125 mL of 8% wine).

3. Any medical or active psychological condition or any clinically relevant laboratory abnormalities, such as, but not limited, to elevated ALT or AST (>3 × upper limit of normal [ULN]) in combination with elevated bilirubin (>2 × ULN), at screening/ baseline that may put the patient at significant risk according to the investigator's judgment, if he/she participates in the clinical study, or may interfere with study assessments (e.g., poor venous access or needle-phobia).

4. Planned or expected major surgical procedure during the clinical study.

5. Patient is unwilling to refrain from using prohibited medications during the clinical study.

6. Currently participating or participated in any other clinical study of a drug or device, within the past 4 months before screening, or is in an exclusion period (if verifiable) from a previous study.

Note: patients who have participated in Cohort 1 of this study may be enrolled to Cohort 2 after a minimum of 4 weeks from last KM-001 dose.

7. Cutaneous infection or another active underlying skin condition, regardless of location.

8. Cutaneous infection of the area to be applied with KM-001, requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics or antifungals, or any topical treatments during and/or up-to 2 weeks before screening.

9. Pregnant or breastfeeding.

10. Failure to convince the investigator of fitness to participate in the study for any other reason.

11. Having received any of the prohibited treatments in Table 4 (Section 5.8) within the specified timeframe before baseline.