Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PC

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 - 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).
• •1. A female patient is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for at least 12 months without an alternative medical cause prior to screening (28).
• •2. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 28 days prior to screening, bilateral tubal occlusion, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), vasectomised/permanently sterile by bilateral orchidectomy partner (given that the partner is the sole sexual partner and has received medical assessment of the surgical success), or sexual abstinence (refraining from heterosexual intercourse during the entire trial/treatment period of risk associated with the IMPs) (28). This period of contraception should be extended for at least 4 weeks after last application of IMP.
• •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:
• •1. Absence of menstrual bleeding for 1 year prior to screening without any other medical reason.
• •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.