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

Summary

The trial is conducted in order to assess the safety of KM-023 and to observe what effects, both beneficial and adverse, it has on the body, and the way the body absorbs and eliminates KM-023, first in healthy participants, then in Olmsted Syndrome patients. In addition, the study will examine the presence of KM-023 in the different layers of the skin. Finally, the efficacy of KM-023 will be investigated in Olmsted Syndrome patients. The first part of this trial will be conducted with healthy participants in France, then after its completion, the second part of the trial will be conducted with Olmsted Syndrome patients in France and the United Kingdom. The first part of the trial is itself divided in two parts: first, a series of single doses will be given to groups of healthy participants, then other groups of healthy participants will be given repeated doses of KM-023 twice daily for 5 days. The participants will be hospitalized approximately 2 days for the investigation of single doses, and approximately 8 days for the investigation of the multiple doses. Some participants will receive the KM-023, and other will receive a placebo, which is a non-active product. Four (4) different dose levels will be given in the trial part studying single administration, and 3 different dose levels in the trial part studying repeated administrations. The trial will start with the lowest doses, and the dose levels will be gradually increased after the safety and tolerability of the previous dose level has been assessed by a group of experts (including physicians). In order to assess the safety, a series of examinations will be conducted, including taking blood samples. Blood samples will also be collected a regular timepoints in order to evaluate the changes in concentration of KM-023 in blood over time. One group of participants will receive a single dose of KM-023 twice: once after fasting, and once with a meal, to check any effect of food on the concentration of KM-023 in blood. In the second part of the trial, Olmsted Syndrome patients will take KM-023 twice daily, for a duration of 12 weeks. There will be a first hospitalization day, during which the patients will receive the study drug, and will be taught how to self-administer KM-023 at home during the ambulatory periods. Safety and efficacy tests will be performed, and the concentration of KM-023 in blood will be monitored. Patients will then go back home with their treatment, to be taken every day. After the first hospitalization day, there will be five visits (two of them will be 1-day hospitalization periods), to monitor the safety and tolerability, the efficacy, and the concentration of KM-023 in blood. Between the hospitalization visits, the clinical teams will call the patients at home on a regular basis to check the safety and tolerability. The duration of participation, including the selection period and the follow-up period, is a maximum 36 days when only one dose is given, 51 days when the dose is given on two occasions to assess the effect of food, 40 days when treatment is given twice daily for 5 days, and 18 weeks in the case of Olmsted Syndrome patients.