KM-001 Cream for the treatment of adult patients with PPPK1 and PC

• Research type

  Research Study

• Full title

  Phase 1b, open label study to evaluate the safety, tolerability, and efficacy of a 1% topical formulation of KM-001 for the treatment of type I Punctate Palmoplantar Keratoderma or Pachyonychia Congenita

• IRAS ID

  1006297

• Contact name

  Anke Mueller

• Contact email

  anke.mueller@bioskincro.com

• Sponsor organisation

  Kamari Pharma Ltd

• ISRCTN Number

  ISRCTN67285394

• Research summary

  Research Summary

  The planned trial intends to evaluate whether a newly developed drug is safe, tolerable, and efficacious for the treatment of type I Punctate Palmoplantar Keratoderma (PPPK1) or Pachyonychia Congenita (PC). Both conditions are rare diseases for which standard therapies are available, which can alleviate the symptoms but cannot cure the disease. The sponsor of the trial - Kamari Pharma Ltd. - is developing a new therapy to cure these diseases. The test product is KM-001 cream 1%., which has not yet been approved for treatment. In this trial, it is tested for the duration of 84 days. All participants are treated with the same test product.
  Patients diagnosed for PPPK1 and PC may participate in the trial which is conducted at the clinical research facility of the Royal London Hospital, Whitechapel, London.
  Overall, the trial will take up to 17 weeks with 8 on-site visits and 4 phone calls. Except for 2 visits the visits will take approximately 90 min with several examinations and assessments including but not limited to blood sampling, blood pressure and heart rate measurement, questionnaires for itch and pain assessment. At two visits, blood samples will be taken at different timepoints after application of the test drug to examine drug levels. These stays will take approximately 6.5 hours.
  Certain medications are not permitted prior to the start and during the trial, i.e., participants may need to discontinue any medications they are taking. Concomitant medications during the trial are allowed after consultation with the investigator if they do not affect the trial results or participants’ safety.
  Based on the research results so far, the sponsor and investigator hope that the treatment with KM-001 cream reduces symptoms, e.g., pain, itch, and the disease severity in treated lesions. However, this is to be proven in the trial

  Summary of Results

  "KM-001 is a topical cream containing TRPV3 channel inhibitor, developed by Kamari Pharma. The drug was assessed in two rare genetic skin disorders: pachyonychia congenita (PC) and punctate palmoplantar keratoderma type 1 (PPPK1). These conditions cause thick, painful calluses—mainly on the soles of the feet—that can greatly affect physical activity (such as walking) and quality of life.
  This UK-based study (KM001-B1B) was an early-stage clinical trial designed to evaluate the safety and initial effectiveness of KM-001 1% cream. A total of 17 adult patients were treated with the cream, applying it twice daily to the soles of the feet, for either 12 weeks (Cohort 1) or 16 weeks (Cohort 2).
  What were the results?
  • Safety: Overall, KM-001 was considered safe and well tolerated during both treatment periods (12 and 16 weeks).
  o No serious side effects related to KM-001 were reported.
  o All side effects were mild to moderate and were reported in 14 of the 17 patients.
  o Only 4 events in 3 patients (18%) were considered possibly related to the study cream, and included mild local skin effects: burning sensation, tingling, stabbing foot pain, and mild redness (erythema).
  o All side effects were localized to the application site and most resolved on their own by the end of the study
  o None of the patients stopped treatment due to side effects.
  o There were no systemic side effects, and no abnormalities were found in blood tests, heart tests (ECG), or vital signs.
  • Pharmacokinetics : Blood samples were collected to measure how much KM-001 entered the bloodstream. Results showed very low systemic absorption: most patients had no detectable levels of the KM-001 in their blood. Even those with measurable levels showed concentrations below levels associated with systemic exposure.
  • Effectiveness: The majority of patients experienced improvement by the end of treatment, based on both clinician and patient assessments, with an increase in “milder” disease classifications. This included improvements in skin appearance, reduction in pain, and better physical function.
  • Pain reduction: In PC patients, up to 50% reported a meaningful reduction in foot pain on week 12 or 16.
  • Improved daily living: Patients and doctors noted increases in the number of “good days” and reduced discomfort when walking.
  • Improvements were consistent across both treatment durations (12 and 16 weeks), with results appearing as early as 4 weeks and maintained through the study.
  Why is this important?
  Currently, there are no approved treatments that target the root cause of PC or PPPK1. The KM001-B1B study shows that KM-001 may offer meaningful relief with a good safety profile, even after a short course of treatment. These results support continued development of the cream in larger clinical studies."

• REC name

  Wales REC 1

• REC reference

  22/WA/0272

• Date of REC Opinion

  28 Oct 2022

• REC opinion

  Further Information Favourable Opinion