A phase 2B, multicenter, randomized, double-blind, placebo-controlled, dose-finding, efficacy and safety study of HRO350 in subjects with mild-to-moderate psoriasis (the ‘HeROPA’ study)

The primary objective of this study is to evaluate the **clinical efficacy** of two oral doses of HRO350 (1050 mg and 2100 mg daily) compared to placebo in patients with mild-to-moderate **psoriasis**. This evaluation aims to determine the recommended dose for phase 3, which is crucial for optimizing therapeutic outcomes and minimizing adverse effects in subsequent trials.

The secondary objective is to assess the long-term safety of two oral doses of HRO350 (1 g and 2 g daily) in subjects with mild-to-moderate psoriasis. This objective is important for understanding the safety profile of the treatment over an extended period, ensuring patient safety and informing clinical practice.

The clinical trial involves a total of **144 participants** diagnosed with **psoriasis**, specifically targeting individuals with mild-to-moderate chronic, active plaque psoriasis. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific criteria, including a Psoriasis Area and Severity Index (PASI) score between 3 and 10, and a Body Surface Area (BSA) of 3 or more at screening and baseline. The trial does not include a vulnerable population. Participants are required to have maintained their condition without systemic treatment for at least six months prior to screening. Additionally, those of childbearing potential must adhere to highly effective birth control methods during the study and for 30 days post-treatment. The trial aims to evaluate the clinical efficacy of two oral doses of HRO350 compared to a placebo, to determine the recommended dose for phase 3.

The clinical trial is a **phase 2B**, multicenter, randomized, double-blind, placebo-controlled, dose-finding study designed to evaluate the efficacy and safety of HRO350 in subjects with mild-to-moderate **psoriasis**. The primary objective is to assess the clinical efficacy of two oral doses of HRO350 (1050 mg and 2100 mg daily) compared to placebo, with the aim of selecting the recommended dose for phase 3. The trial is expected to run from March 2023 to April 2025, with an estimated duration of 52 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of chronic plaque psoriasis, and specific **Psoriasis Area and Severity Index (PASI)** scores. Following successful screening, participants will be randomized to receive either HRO350 or placebo. Study visits will occur at regular intervals to monitor efficacy and safety endpoints, including PASI50, Static Physician’s Global Assessment (sPGA), and Body Surface Area (BSA). Safety assessments will include adverse events, biochemical and hematological lab tests, and discontinuation rates.

The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, require rescue medication, or fail to adhere to the study protocol. The trial's design ensures that all data collected will contribute to determining the optimal dosing strategy for future studies.

The clinical trial involves the use of **BETAMETHASONE VALERATE**, a topical **ointment** formulated for the treatment of mild-to-moderate psoriasis. The active substance, betamethasone valerate, is a chemical compound applied topically. The maximum daily dose is 10 grams, with a total maximum dose of 100 grams over a treatment period of up to 4 weeks. The ointment is not a pediatric formulation and is used as an auxiliary treatment in the trial.

The experimental medication **HRO350** contains the active substance **PEHERO**, which is a mixture of phospholipid esters derived from herring roe oil. This medication is provided in the form of soft capsules for **oral use**. The trial evaluates two oral doses: 1050 mg and 2100 mg daily, with a maximum daily dose of 2 grams and a total maximum dose of 728 grams over a 52-week treatment period. The primary objective is to assess the clinical efficacy of HRO350 in subjects with mild-to-moderate psoriasis, aiming to determine the recommended dose for phase 3 trials.

The study also includes a **placebo** control, consisting of inert refined sunflower oil provided in 1000 mg fill-weight oblong soft capsules. Each capsule contains 998 mg of refined sunflower oil, along with 2 mg of dl-alpha-tocopherol as an antioxidant, red iron oxide for colorization, and liquid peach flavor for aromatization. The placebo is used to ensure the double-blind nature of the trial, allowing for a comparison of the efficacy and safety of HRO350 against a non-active treatment.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of patients achieving **PASI50**, which is defined as a 50% or greater reduction in the Psoriasis Area and Severity Index (PASI) score from baseline to week 26. This endpoint is crucial for determining the effectiveness of the treatment in reducing the severity of psoriasis symptoms.

Secondary endpoints include a variety of measures to provide a comprehensive evaluation of treatment efficacy. These include the Static Physician's Global Assessment (sPGA), Body Surface Area (BSA) affected by psoriasis, the product of sPGA and BSA, and the Scalp PGA (ScPGA) Scale. Additionally, the use of rescue medication, Dermatology Life Quality Index (DLQI), SF-36 health survey, Psoriasis Symptom Inventory (PSI), and Treatment Satisfaction Score (TSS) will be assessed. Safety endpoints will also be monitored, including adverse events, biochemical and hematological laboratory tests, and discontinuation rates.

The trial is designed to evaluate the clinical efficacy of two oral doses of HRO350 (1050 mg and 2100 mg daily) compared to placebo in patients with mild-to-moderate psoriasis. The study aims to select the recommended dose for phase 3 based on these efficacy assessments. The schedule for measuring and collecting these parameters will be aligned with the trial's timeline, with key assessments occurring at baseline, week 26, and other specified timepoints throughout the study duration.