Phase II Study of Itacitinib in Non-Severe Hemophagocytic Lymphohistiocytosis in Adults

The primary objective of this Phase II prospective trial is to evaluate the **overall response rate (RR)**, defined as achieving a complete response (CR) or a partial response (PR) at day 15 of treatment with **Itacitinib** in adult patients with non-severe Hemophagocytic Lymphohistiocytosis (HLH). This objective is clinically relevant as it aims to assess the efficacy of Itacitinib in improving clinical and biological symptoms in patients with primitive, refractory, or relapsed non-severe HLH. The trial focuses on determining the potential of Itacitinib as a therapeutic option for this patient population.

The clinical trial involves **adult patients** diagnosed with non-severe hemophagocytic lymphohistiocytosis (HLH). The study population includes both male and female participants aged 18 years and older. Participants are required to have either front-line or recurrent sporadic HLH without associated pathologies that may benefit from specific treatment, and they must not exhibit severity criteria or organ failure. The trial does not involve a vulnerable population. The sponsor has not provided the total number of participants. Key lifestyle considerations include the requirement for women of childbearing potential to have a negative pregnancy test and to use reliable contraception throughout the study. Participants must be willing to provide written informed consent and comply with the study protocol. The selection criteria emphasize specific clinical features such as cytological evidence of hemophagocytosis, fever, and splenomegaly, along with laboratory findings like cytopenia, hypertriglyceridemia, and elevated ferritin levels. Participants must also meet an HScore of 169 or higher and be affiliated with a social security category.

The clinical trial is designed to evaluate the efficacy of **Itacitinib** in treating non-severe Hemophagocytic Lymphohistiocytosis (HLH) in adult patients. This is a Phase II, prospective, randomized, double-blind, controlled trial. The trial aims to assess the overall response rate, defined as achieving a complete or partial response at day 15 of treatment, based on clinical and biological symptoms. The trial is expected to run from May 2022 to August 2026, with participant involvement lasting up to six months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, absence of severe organ failure, and cytological features of hemophagocytosis. Major criteria include fever and splenomegaly, while minor criteria involve adenopathies and specific blood count thresholds. A negative pregnancy test is required for women of childbearing potential, who must also use reliable contraception throughout the study.

Following the screening, participants will be randomized to receive either the investigational product or a control. The study includes regular follow-up visits to monitor safety, efficacy, and adherence to the protocol. The end-of-study visit will evaluate the primary endpoint, which is the overall response rate at day 15. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the protocol, or withdraw consent. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent before enrollment.

The clinical trial involves the administration of **Itacitinib**, an experimental medication, for the treatment of non-severe Hemophagocytic Lymphohistiocytosis (HLH). **Itacitinib** is provided in the form of a **tablet** and is intended for **oral use**. The maximum daily dose of **Itacitinib** is 400 mg, with a total maximum dose of 72 grams over the course of the treatment. The treatment period is set to a maximum of 6 months. The active substance, **Itacitinib**, is of chemical origin and is manufactured by Incyte Corporation. The medication is not formulated for pediatric use and is not classified as an orphan drug.

In this study, **Itacitinib** is the primary investigational product, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial aims to evaluate the overall response rate, defined as achieving a complete or partial response by day 15 of treatment, based on clinical and biological symptoms in adults with primitive, refractory, or relapsed non-severe HLH. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

Efficacy in the clinical trial titled "HLH-JAK - Treatment of non-severe Hemophagocytosis Lymphohistiocytosis with ITACITINIB" will be assessed primarily through the **overall response rate (RR)**. This is defined as achieving either a Complete Response (CR) or a Partial Response (PR) at day 15 of ITACITINIB treatment. The assessment will focus on clinical and biological symptoms in patients with primitive, refractory, or relapsed non-severe adult Hemophagocytosis Lymphohistiocytosis (HLH). The primary endpoint is the achievement of CR or PR, which will be evaluated at the specified timepoint of day 15. The trial will utilize clinical evaluations and biological markers to determine the response rate, ensuring a comprehensive assessment of the treatment's efficacy.