A multicenter, double-blind, randomized, placebo-controlled, parallel-group, twelve-week treatment proof-of-concept trial to explore the efficacy and safety of IDOR-1117-2520 in adults with moderate to severe chronic plaque psoriasis with or without psoriatic arthritis.

The primary objective of this study is to explore the efficacy of IDOR-1117-2520 compared to placebo on Psoriasis Area and Severity Index (PASI) score in participants with moderate to severe chronic plaque psoriasis. The PASI score represents a validated clinical tool for quantifying disease severity and extent, making it a clinically relevant endpoint for assessing therapeutic response in psoriatic disease.

The secondary objectives include:

• To compare the effect of IDOR-1117-2520 to placebo on static physician's global assessment (sPGA) score in participants with moderate to severe chronic plaque psoriasis.

• To evaluate the safety and tolerability of IDOR-1117-2520 during 12 weeks of treatment in participants with moderate to severe chronic plaque psoriasis.

This clinical trial enrolled a total of **12 participants** diagnosed with **moderate to severe chronic plaque psoriasis**. The study population included both **male and female subjects** comprising **adults** and **elderly individuals**. Participants were selected based on having stable chronic plaque psoriasis for at least 6 months prior to screening, with or without **psoriatic arthritis**. Key selection criteria required a **Psoriasis Area and Severity Index (PASI) score** of 12 or higher, a **static physician's global assessment (sPGA) score** of 3 or higher, and at least 10% affected body surface area at both screening and randomization. Eligible participants were required to be candidates for **systemic therapy**, including **phototherapy**, as determined by the investigator. Female participants of childbearing potential were required to have negative pregnancy tests and utilize highly effective contraceptive methods throughout the trial period and for 30 days following discontinuation of the trial intervention, with monthly pregnancy testing conducted during the study. The trial included a **vulnerable population**.

This is a multicenter, double-blind, randomized, placebo-controlled, parallel-group clinical trial designed to explore the efficacy and safety of IDOR-1117-2520 in adults with moderate to severe chronic plaque psoriasis with or without psoriatic arthritis. The trial is classified as a Phase 2 study. The investigational medicinal product IDOR-1117-2520 is administered as a gastro-resistant tablet via the oral route, with the active substance IDOR-1117-2520C of chemical origin. A matching placebo is used as the control intervention. The maximum treatment period is 12 weeks.

The primary objective is to explore the efficacy of IDOR-1117-2520 compared to placebo on Psoriasis Area and Severity Index (PASI) score in participants with moderate to severe chronic plaque psoriasis. The primary endpoint is the change from baseline to Week 12 in PASI score. Secondary endpoints include achievement of static physician's global assessment (sPGA) score clear (0), almost clear (1) and at least 2 points improvement from baseline to each time point up to Week 12, as well as change from baseline and ratio to baseline at each time point up to Week 16 in sPGA score. Safety assessments include monitoring of adverse events (AEs) leading to premature discontinuation of trial intervention, treatment-emergent AEs and serious adverse events (SAEs), changes in vital signs, body weight, clinical laboratory variables, and 12-lead electrocardiogram (ECG), as well as treatment-emergent marked abnormalities for these parameters.

Principal inclusion criteria require participants to have stable moderate to severe chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before screening, confirmed by clinical diagnosis. At both screening and randomization, participants must have a PASI score of at least 12, an sPGA score of at least 3, and affected body surface area of at least 10 percent. Participants must be candidates for systemic therapy, including phototherapy, for psoriasis treatment as judged by the investigator. Participants of childbearing potential must have a negative pregnancy test at screening and randomization, agree to use a highly effective method of contraception from screening up to 30 days after permanent trial intervention discontinuation, be sexually inactive, or have a vasectomized partner, and agree to undertake monthly urine pregnancy tests during the trial and up to at least 30 days after discontinuation of trial intervention.

The estimated recruitment start date is November 28, 2025, with an estimated trial end date of November 30, 2026. The overall duration of participant involvement in the trial is approximately 16 weeks, including the 12-week treatment period followed by follow-up assessments. Conditions that may lead to early termination from the study include adverse events requiring premature discontinuation of trial intervention or other safety concerns as determined by the investigator.

The experimental medication **IDOR-1117-2520** is administered as a **gastro-resistant tablet** formulation. The active substance contained in this investigational medicinal product is **IDOR-1117-2520C**, which is of chemical origin. The route of administration is **oral**. The maximum treatment period for this investigational product is **12 weeks**. The sponsor product code assigned to this medication is IDOR-1117-2520, and it is manufactured by Idorsia Pharmaceuticals Ltd.

A **matching placebo** is utilized as the comparator treatment in this trial. The placebo is designed to match the appearance of the experimental medication IDOR-1117-2520 to maintain blinding throughout the study. The placebo does not contain any active pharmaceutical ingredients. Participants randomized to the placebo arm receive this inactive comparator for the same duration as those receiving the experimental treatment, ensuring consistency in the study design and enabling valid comparison of efficacy and safety outcomes between treatment groups.

Efficacy will be assessed using the Psoriasis Area and Severity Index (PASI) score as the primary efficacy parameter. The primary endpoint is the change from baseline to Week 12 in PASI score. Secondary efficacy endpoints include the achievement of static physician's global assessment (sPGA) score of clear (0) or almost clear (1) with at least 2 points improvement from baseline at each time point up to Week 12. Additionally, the change from baseline and ratio to baseline at each time point up to Week 16 in sPGA score will be evaluated. Eligibility for the trial requires participants to have a PASI score of 12 or greater, sPGA score of 3 or greater, and affected body surface area of 10% or greater at both screening and randomization. Assessments will be conducted at multiple time points throughout the twelve-week treatment period and extended to Week 16 for certain parameters.