Efficacy and Safety of Itacitinib in Adults with Diffuse Systemic Sclerosis: A Phase II Randomized Controlled Trial

The primary objective of this study is to demonstrate a reduction in **skin fibrosis** in patients with diffuse systemic sclerosis (SSc) after 360 days of treatment with itacitinib, as assessed by the modified Rodnan skin score, compared to those receiving a placebo. This is clinically relevant as skin fibrosis is a significant manifestation of SSc, impacting patient morbidity and quality of life. A reduction in skin fibrosis could indicate a potential therapeutic benefit of itacitinib in managing this condition.

Secondary objectives include evaluating the safety profile of itacitinib in patients with SSc and comparing its efficacy against placebo in terms of disease activity, quality of life, and disability. These objectives are crucial for understanding the overall therapeutic value and risk-benefit profile of itacitinib in this patient population.

The clinical trial involves **patients with newly or active diffuse Systemic sclerosis (SSc)** at the time of screening. The study population includes both male and female adults aged 18 years and older. Participants are required to have a diagnosis of SSc as defined by the American College of Rheumatology/EULAR 2013 criteria, with a disease duration of less than 36 months or active disease as per the EUSTAR disease activity score. The trial includes individuals with a modified Rodnan skin score between 10 and 35 units at screening. Participants must be able to provide written informed consent and be affiliated with a social security scheme. Women of childbearing potential must have a negative pregnancy test and use reliable contraception throughout the study. The trial population is selected based on these criteria, and the sponsor has not provided the total number of participants. Lifestyle considerations such as stable doses of mycophenolate or methotrexate for at least two months prior to randomization are relevant for those receiving these treatments. The trial includes a vulnerable population, but specific details on lifestyle factors such as diet or physical activity are not provided.

The clinical trial is a **randomized**, controlled study designed to evaluate the safety and efficacy of **itacitinib** in adults with diffuse **systemic sclerosis** (SSc). The trial is structured as a **double-blind** study, ensuring that neither the participants nor the investigators are aware of the treatment assignments, which include either itacitinib or a placebo. The primary objective is to assess the reduction in skin fibrosis, as measured by the modified Rodnan skin score, over a treatment period of 360 days. The trial is expected to conclude by December 31, 2025, with recruitment having commenced on February 2, 2023.

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 SSc, and disease activity. Following randomization, participants will attend regular follow-up visits to monitor treatment effects, safety, and adherence to the study protocol. The primary endpoint is the change in the modified Rodnan skin score at 360 days, while secondary endpoints include the security profile, SSc disease activity, and quality of life assessments. The end-of-study visit will occur at the conclusion of the treatment period, where final evaluations will be conducted.

Participant involvement is expected to last for the entire 360-day treatment period, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent and meet the inclusion criteria, such as a stable dose of mycophenolate or methotrexate if applicable. The study aims to provide valuable insights into the potential benefits of itacitinib for patients with diffuse systemic sclerosis.

The clinical trial involves the administration of **Itacitinib**, an experimental medication, to evaluate its safety and efficacy in adults with systemic sclerosis. **Itacitinib** is provided in a **tablet** form and is administered orally. The maximum daily dose is 200 mg, with a total maximum dose of 72 grams over the course of the study. The treatment period extends up to 360 days. The active substance in the medication is **Itacitinib**, a chemical compound developed by Incyte Corporation. Participants' compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen.

In addition to the experimental treatment, a **placebo** is used as a comparator in this randomized, controlled trial. The placebo is designed to mimic the appearance of the **Itacitinib** tablet but does not contain the active substance. It is also administered orally, following the same dosing schedule as the experimental medication. The use of a placebo allows for the assessment of **Itacitinib**'s efficacy by comparing outcomes between the treatment and control groups. The trial aims to demonstrate a reduction in skin fibrosis, as measured by the modified Rodnan skin score, in patients receiving **Itacitinib** compared to those receiving the placebo.

Efficacy in this clinical trial will be assessed primarily through the change in the modified Rodnan skin score (mRSS) at 360 days. The mRSS is a validated tool used to evaluate the extent of skin fibrosis in patients with **systemic sclerosis** (SSc). This score will be measured at the end of the treatment period to determine the effectiveness of itacitinib compared to a placebo. Secondary endpoints include the assessment of the security profile, SSc disease activity, and quality of life and disability. These parameters will provide a comprehensive evaluation of the treatment's impact on patients' overall health and disease progression. The trial is designed to ensure that data collection and analysis are conducted systematically and objectively, adhering to established clinical trial protocols.