Evaluation of Dupilumab and Fexofenadine Hydrochloride in Indolent Systemic Mastocytosis with Cutaneous Involvement

The primary objective of this study is to compare the effects of treatment with **dupilumab**, a monoclonal antibody, and **fexofenadine**, a standard antihistamine, in patients with indolent systemic mastocytosis with skin involvement. This comparison is clinically relevant as it aims to evaluate the efficacy of dupilumab, which could potentially offer a novel therapeutic approach for managing symptoms associated with this condition.

Secondary objectives include:

• Assessing the frequency of inflammatory symptoms caused by mast cells, primarily focusing on anaphylaxis and skin redness per week.
• Evaluating the extent of skin lesions and the severity of skin itching.
• Testing serum tryptase concentration and examining for possible liver and spleen enlargement.
• Improving the quality of life assessment for patients.
• Determining the frequency of depressive symptoms.
• Assessing fatigue symptoms using the Fatigue Impact Scale.

The clinical trial involves participants diagnosed with **systemic mastocytosis** with a slow course and skin involvement. The study population includes both male and female subjects, aged between 18 and 65 years. Participants are selected based on specific criteria, including a moderate additional risk of disease impairing quality of life, as assessed by various scales and questionnaires. The trial does not specify the total number of participants, as the sponsor has not provided this information. The study population is characterized by a vulnerability due to the nature of the disease, and lifestyle factors such as diet and physical activity are not explicitly mentioned. Key inclusion criteria focus on the extent and impact of skin lesions, intensity of itching, and quality of life indices. The trial aims to compare the effects of treatment with dupilumab and fexofenadine, a standard antihistamine treatment.

The clinical trial is designed to evaluate the efficacy of **dupilumab** in the treatment of indolent systemic mastocytosis with skin involvement. This study is a randomized, double-blind, controlled trial comparing the effects of dupilumab with fexofenadine, a standard antihistamine treatment. The trial is expected to commence on January 1, 2025, and conclude by July 31, 2029, with a total duration of approximately 4.5 years. Participants will be involved in the study for a maximum treatment period of 16 weeks.

The trial will include several study visits, beginning with an inclusion (screening) visit to assess eligibility based on the principal inclusion criteria, such as a diagnosis of systemic mastocytosis with skin involvement and specific quality of life impairments. Follow-up visits will be scheduled to monitor the primary endpoints, which include reducing symptoms caused by mast cell mediators, decreasing the extent of skin lesions, and improving quality of life. Secondary endpoints will assess the quality of life in mastocytosis and the incidence of life-threatening anaphylactic reactions. The end-of-study visit will evaluate the overall outcomes and any adverse events experienced by participants.

Participants are expected to adhere to the study protocol for the entire duration unless conditions arise that necessitate early termination, such as significant adverse reactions or non-compliance with study procedures. The trial aims to provide comprehensive data on the therapeutic benefits of dupilumab in this patient population, contributing to the understanding and management of systemic mastocytosis with skin involvement.

The clinical trial involves the use of **Dupixent** (dupilumab), a **solution for injection** in a pre-filled syringe, as the experimental medication. Dupixent is administered subcutaneously with a dosage of 300 mg. The maximum daily dose is 600 mg, and the total dose over the treatment period can reach up to 2700 mg. The treatment period is set for a maximum of 16 weeks. Dupilumab is a protein-based therapeutic agent, specifically classified under the ATC code D11AH05. The administration of Dupixent is monitored to ensure participant compliance throughout the trial.

The study also includes a **comparator treatment** with Telfexo, which contains **fexofenadine hydrochloride** as the active substance. Telfexo is provided in the form of a **film-coated tablet** with a dosage of 180 mg. The maximum daily dose is 180 mg, and the total dose over the treatment period can reach up to 20160 mg. This medication is administered orally and serves as a standard second-generation antihistamine treatment. The treatment period for Telfexo is also set for a maximum of 16 weeks.

A **placebo** is utilized in the trial, specifically PL2, which is a placebo for Telfexo 180 mg. The placebo is used to maintain the blinding of the study and to provide a control for evaluating the efficacy of the experimental and comparator treatments. The pharmaceutical form and administration details of the placebo are not specified.

Additionally, **Injectio Natrii Chlorati Isotonica Polpharma** is used as a solvent for preparing parenteral medications. This solution contains **sodium chloride** at a concentration of 9 mg/ml and is classified under the ATC code V07AB. The maximum daily dose is 4 ml, with a total dose of up to 18 ml over the treatment period. This solution is administered via injection and is used to ensure the proper preparation and administration of the study medications.

The clinical trial aims to assess the efficacy of **dupilumab** in the treatment of indolent systemic mastocytosis with skin involvement. Efficacy will be evaluated using several primary endpoints, including the reduction in the incidence of symptoms caused by the release of mast cell mediators, such as anaphylaxis and flushing, measured weekly. Additionally, the trial will assess the reduction in the extent of skin lesions using the Body Surface Area (BSA) assessed according to the Wallace 9 principles, reduction in itch severity using the Visual Analog Scale (VAS), improvement in quality of life using the Mastocytosis Quality of Life (MC-QoL) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30), and reduction in symptoms of depression and fatigue using the Hamilton Rating Scale for Depression and the Fatigue Impact Scale, respectively.

Secondary endpoints include the Quality of Life in Mastocytosis (QLMS) Questionnaire, the incidence of life-threatening anaphylactic reactions, and decreased concentrations of tryptase, IL4, and IL13 in peripheral blood serum. The trial will compare the effects of treatment with **dupilumab** against fexofenadine, a standard antihistamine treatment. The efficacy parameters will be collected and analyzed at specified intervals throughout the trial duration, which is estimated to conclude by July 31, 2029. The trial is categorized as a therapeutic confirmatory clinical trial, indicating its focus on confirming the therapeutic benefits of the investigational drug.