KM-023 in healthy adults and people with Olmsted syndrome

A Combined Single and Multiple Ascending Dose Phase 1a/1b, Double-blind, Placebo-Controlled, and Food-effect Study to Evaluate the Safety and Pharmacokinetics of Oral KM-023 in Healthy Participants. Followed by a 3-month Open Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Oral KM-023 in Olmsted Syndrome Patients

This early-phase test gives the experimental drug KM-023 first to healthy adults and then to people with Olmsted syndrome to check safety, how the body and skin handle the drug, and whether it helps symptoms.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Kamari Pharma Ltd (Research network)
• Locations: 1 site (Rennes)
• Trial ID: NCT07090889 on ClinicalTrials.gov

What this trial studies

This phase 1, randomized, placebo-controlled trial begins with single- and multiple-dose cohorts in healthy volunteers in France to characterize safety, tolerability, systemic pharmacokinetics, and skin penetration of KM-023. After completion of the healthy cohorts, the trial will enroll people with Olmsted syndrome in France and the United Kingdom to collect additional safety data and preliminary evidence of symptom benefit. Participants receive KM-023 or placebo, with healthy volunteers hospitalized briefly around dosing and patient cohorts followed through planned dosing regimens. The protocol includes contraception and medication restrictions and measures drug levels in blood and different skin layers alongside clinical assessments.

Who should consider this trial

Good fit: Adults with a confirmed diagnosis of Olmsted syndrome who meet the study's health, contraception, and medication restrictions and can attend visits in France or the United Kingdom are the intended patient participants.

Not a fit: People who are pregnant, have significant liver or kidney disease, are current smokers, or cannot comply with clinic visits or medication restrictions are unlikely to be eligible or to receive benefit.

Why it matters

Potential benefit: If successful, KM-023 could offer a targeted treatment that reduces painful skin thickening and fissures in people with Olmsted syndrome.

How similar studies have performed: This is an early-stage, partly first-in-human effort and similar targeted treatments for Olmsted syndrome are limited, so clinical success has not been widely demonstrated.

Eligibility criteria

Inclusion Criteria:

Part A

* Healthy female and male participants.
* Female participants of non-childbearing potential, childbearing potential and males capable of fathering a child must meet the contraception requirements.
* Non-smoking and no use of any tobacco or nicotine products (by declaration) for a period of at least 1 month prior to screening visit.
* Not using prescription medication 14 days prior to admission; and 7 days prior to admission for over the counter (OTC) medication/vitamins/supplements.
* Must not be taking any medication that could potentially impair hepatic or renal function at the time of screening.
* No history of alcohol or other drugs of abuse.
* Body Mass Index (BMI) of 18.0 to 32.0 kg/m2 (inclusive); and a total body weight \>50.0 kg (110 lbs) and \<100.0 kg (220 lbs) at screening and Day -1.
* No vaccines given within 14 days of dosing.
* Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research.

Part B

* Read, understood, and signed an ICF before any investigational procedure(s) are performed.
* Clinical diagnosis of OS, with confirmed TRPV3 or PERP mutation, and visible palmoplantar keratoderma.
* Stable medical condition over the previous 1 month.
* Willingness and ability to comply with the treatment and follow-up visits.
* Willingness to refrain from current treatments, in compliance with the list of prohibited medications.
* No contraindications to study medication as determined by the Investigator.
* Female participants of non-childbearing potential, childbearing potential and males capable of fathering a child must meet the contraception requirements.
* Negative serum pregnancy test at screening, and negative urinary pregnancy test at Day -1.

Exclusion Criteria:

Part A

* Participants who are staff members at the investigational site directly involved in conducting the study.
* Evidence or history of clinically relevant hepatic, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease.
* History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within 6 months of screening.
* Screening supine BP ≥145 mm Hg (systolic) or ≥90 mm Hg (diastolic)
* Participants with any abnormalities in clinical laboratory tests, and serology results, at screening, considered by the study physician as clinically significant.
* Pregnant or breastfeeding female participants.
* Participants who donated blood or received blood or plasma derivatives in the 30 days preceding study drug administration.
* Dosed in another clinical trial within at least 10 tissue half-lives prior to dosing or 4 months.
* Known relevant allergy to any drug or excipients in the formulation
* Participants with any acute medical situation (e.g., acute infection) within 48h of screening or start of dosing, which is considered of significance by the Investigator.
* Major surgery within the last 3 months or any planned surgery during the trial.
* Unwilling or unable to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures and the restrictions described in the protocol.
* Any other condition or previous therapy that, in the opinion of the Investigator or their designee, would render the participant unsuitable for this study, including an inability to fully comply with the study protocol requirements or a likelihood of noncompliance with study procedures.

Part B

* The presence of other significant dermatological conditions that could interfere with the evaluation of the study treatment's safety and efficacy.
* Active or uncontrolled infections (e.g., sepsis, tuberculosis, hepatitis B or hepatitis C at the screening visit, human immunodeficiency virus\[HIV\]) that could complicate participation in the study.
* Any medical or active psychological condition or any clinically relevant laboratory abnormalities, such as, but not limited, to elevated ALT or AST (\> 3 × ULN) in combination with elevated bilirubin (\> 2 × ULN), at the screening/baseline visit.
* Diabetic foot ulcers.
* Patient is unwilling to refrain from using prohibited medications during the clinical trial.
* Currently participating or participated in any other clinical trial of an IMP or device, within the past 4 months before the screening visit.
* Cutaneous infection or another underlying condition of the skin which may impact the assessments or trial participants.
* 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.
* Pregnant or breastfeeding patient.
* Having received any of the prohibited treatments in Table 2 within the specified timeframe before inclusion.
* Known relevant allergy to any drug or excipients in the formulation.
* Major surgery within the last 3 months, or minor surgery (requiring local anesthetic) during last 1 month, or any planned surgery during the trial.
* Unwilling or unable to comply with all scheduled visits, treatment plan, laboratory tests and other study procedures and the restrictions described in the protocol.
* Any other condition or previous therapy that, in the opinion of the Investigator or their designee, would render the patient unsuitable for this study, including an inability to fully comply with the study protocol requirements or a likelihood of noncompliance with study procedures.

Where this trial is running

Rennes

• Biotrial — Rennes, France (Recruiting)

Conditions Olmsted Syndrome