Type I Punctate Palmoplantar Keratoderma (PPPK1) or Pachyonychia Congenita (PC) Skin and Connective Tissue Diseases
Conditions
Interventions
Current interventions as of 30/10/2025:
2 cohorts of patients in an open-label study: Twice daily topical applications of 2gr KM-001 1% cream on the plantar surfaces for 84 consecutive days with a 1
Sponsors
Kamari Pharma Ltd.
Eligibility
Sex/Gender
All
Age
16 Years to 75 Years
Inclusion criteria
Inclusion criteria: Current key inclusion criteria as of 30/10/2025: 1. Read, understood, and signed an informed consent form (ICF) before any investigational procedure(s) are performed. 2. Male and female and aged 16 – 75 years (inclusive) at the time of screening. 3. Clinical diagnosis of: • Punctate palmoplantar keratoderma type I disease with confirmed heterozygous mutation in AAGAB gene. OR • PC with confirmed heterozygous mutation in either KRT16, KRT17, KRT6A, KRT6B or KRT6C mutations. 4. The target treatment region is 0.5% to 4% BSA including target lesion. 5. CGI-S score (as assessed by the CI at the screening visit) of =2. 6. Female patients of childbearing potential1 must use a highly effective birth control method2 (failure rate ?1% per year when used consistently and correctly) (28) throughout the trial and for at least 4 weeks after last application of IMP. In addition to the hormonal contraception, female patients must agree to use a supplemental barrier method during intercourse with a male partner (i.e., male condom) throughout the trial and for at least 4 weeks after last application of IMP. Female patients must be having regular menstrual periods (interval of 21 to 35 days, duration of 2 to 7 days for several months) at the baseline visit (as reported by the patient); exception: patients using hormonal contraceptives that preclude regular menstrual periods, menopausal or hysterectomised patients. A male patient with a pregnant or non-pregnant female partner of childbearing potential1 must use adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice; as a minimum, the male patient must agree to use condom during treatment and until the end of relevant systemic exposure in the male patient (7 days post-treatment). 7. Female patients must refrain from donating eggs throughout the trial and for 4 weeks after the last IMP administration. Male patients must refrain from sperm donation throughout the trial and for 7 days after the last IMP administration. 8. Female patients of non-childbearing potential must meet 1 of the following criteria: 8.1. Absence of menstrual bleeding for 1 year prior to screening without any other medical reason. 8.2. Documented hysterectomy or bilateral oophorectomy at least 3 months before the trial. 9. Patient is willing and able to comply with all the time commitments and procedural requirements of the protocol. _____ Previous key inclusion criteria: 1. Read, understood, and signed an informed consent form (ICF) before any investigational procedure(s) are performed. 2. Male and female and aged 18 – 65 years (inclusive) at the time of screening. 3. Clinical diagnosis of: • Punctate palmoplantar keratoderma type I disease with confirmed heterozygous mutation in AAGAB gene. OR • PC with confirmed heterozygous mutation in either KRT16, KRT17, KRT6A, KRT6B or KRT6C mutations. 4. The target treatment region is 0.5% to 4% BSA including target lesion. 5. CGI-S score (as assessed by the CI at the screening visit) of =2. 6. Female patients of childbearing potential1 must use a highly effective birth control method2 (failure rate ?1% per year when used consistently and correctly) (28) throughout the trial and for at least 4 weeks after last application of IMP. In addition to the hormonal contraception, female patients must agree to use a supplemental barrier method during intercourse with a male partner (i.e., male condom) throughout the trial and for at least 4 weeks
Exclusion criteria
Exclusion criteria: 1. History of drug or alcohol abuse in the past 2 years. 2. Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine). 3. Positive hepatitis B surface antigen [HbsAg], hepatitis B core antibody [HbcAb], hepatitis C antibody, or human immunodeficiency virus (HIV) antibody serology results at the screening visit. 4. Known hypersensitivity or any suspected cross-allergy to the API and/or excipients. 5. Any medical or active psychological condition or any clinically relevant laboratory abnormalities, such as, but not limited, to elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (>3 × upper limit of normal [ULN]) in combination with elevated bilirubin (>2 × ULN), at the screening/baseline visit. 6. Planned or expected major surgical procedure during the clinical trial. 7. Patient is unwilling to refrain from using prohibited medications during the clinical trial. 8. Currently participating or participated in any other clinical trial of an IMP or device, within the past 4 months before the screening visit. 9. Cutaneous infection or another underlying condition of the skin which may impact the assessments or trial participation. 10. Cutaneous infection of the area to be treated with IMP within 2 weeks before the screening visit or any infection of treatment area requiring treatment with oral, parenteral antibiotics, antivirals, antiparasitics or antifungals or any topical within 2 weeks before the screening visit. 11. Pregnant or breastfeeding patient. 12. Failure to satisfy the investigator of fitness to participate for any other reason. 13. Having received any of the prohibited treatments within the specified timeframe before the baseline visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 05/11/2025: 1. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) measured by patient diary report, directed safety questioning, physical examination, and review of clinical laboratory abnormalities at each on-site and phone visit from Day 0 through End of Study. Events coded with MedDRA and graded per CTCAE, with causality assessed by the investigator. 2. Clinical laboratory parameters (chemistry, hematology, serology, and standard urinalysis) measured using blood and urine samples at Screening, Baseline, Day 7, Day 84, Day 112, Day 140 (Cohort 2 only), and Early Termination (ET, if applicable). 3. Vital signs (body temperature, pulse, blood pressure) measured using calibrated clinical devices at all in-clinic visits. 4. Electrocardiogram (ECG) parameters (e.g., QTcF, PR, QRS, heart rate) measured using 12-lead ECG at Screening, Baseline, Day 84, Day 112, Day 140 (Cohort 2 only), and Early Termination (ET, if applicable). _____ Previous primary outcome measures: 1. Incidence rate of TEAEs and SAEs grouped by body system up to the patient´s end of trial (Day 112 [Visit 12]) or early termination [ET] visit]). 2. Mean changes from baseline (Day 1) in clinical laboratory parameters to Day 84 (end of treatment [EoT]) and from Day 84 (EoT) to Day 112. 3. Mean changes from baseline (Day 1) in vital signs (body temperature, pulse, blood pressure) to Day 84 (EoT) and from Day 84 (EoT) to Day 112. 4. Mean changes from baseline (Day 1) in ECG parameters to Day 84 (EoT) and from Day 84 (EoT) to Day 112. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 05/11/2025: 1. Percent of responders on end of treatment (EoT) (Day 84 for cohort 1, Day 112 for cohort 2) compared to baseline (Day 0); a responder is defined to have an improvement in at least 1 parameter of the following parameters: 1.1. Patient Global Impression of Severity (PGI-S) (at least 1 unit improvement). Measured at each on-site visit from Day 0 through End of Study and Early Termination (ET, if applicable). 1.2. Clinical Global Impression of Severity (CGI-S) (at least 1 unit improvement). Measured at each on-site visit and Early Termination (ET, if applicable). 1.3. Peak Pruritus Numerical Rating Scale (PP-NRS) score (reduction of at least 4 points compared to baseline, i.e., change from baseline <= 4). Measured from Day 0 through End of Study and Early Termination (ET, if applicable). 1.4. Patient Global Impression of Change (PGI-C) (response at EoT: very much improved or much improved or minimally improved). Measured at each on-site visit from Day 0 through End of Study and Early Termination (ET, if applicable). 1.5. Visual Analogue Scale (VAS) pain score (A reduction of at least 10 points).Measured at each on-site visit from Day 0 through End of Study and Early Termination (ET, if applicable). _____ Previous secondary outcome measures: 1. Percent responders in CGI-S scale (0= “none” to 4= “very severe”) on Day 84 [Visit 10, EoT] compared to baseline (Day 1); a responder is defined to have an improvement of at least 2 points in disease severity on Day 84 [Visit 10, EoT] compared to baseline (Day 1). 2. Mean change from baseline (Day 1 [Visit 2] to Day 84 [Visit 10, EoT]) in PGI-S. 3. Mean change from baseline (Day 1 [Visit 2] to Day 84 [Visit 10, EoT]) in PGI-C. | — |
Countries
England, United Kingdom
Outcome results
None listed