A 24-week with possible extension, prospective, multicenter, randomized, double blind, placebo-controlled, 2-parallel group with a randomization 1:1, phase III study to compare efficacy and safety of oral masitinib to placebo in treatment of patients with Smouldering or Indolent Severe Systemic mastocytosis with handicap, unresponsive to optimal symptomatic treatment

This trial is for adults aged 18 and older who have been diagnosed with indolent or smouldering systemic mastocytosis. These are forms of the condition that develop slowly but can still cause very troublesome daily symptoms.

To be considered, participants must have severe, disabling symptoms—such as intense fatigue, frequent flushing, severe itching, or persistent digestive problems—that have not improved enough with standard symptom-relieving medications.

The trial team will check each person's general health to make sure taking part is safe. People who have certain other serious health conditions, significant liver or kidney issues, or who are pregnant or breastfeeding may not be able to join.

Taking part lasts for at least 24 weeks, with the possibility of staying on the study longer if it helps. Participants take their assigned study tablets once or twice a day by mouth. Half of the people taking part will receive masitinib and half will receive an inactive dummy pill (placebo). Neither you nor your study doctor will know which treatment you are taking, which helps keep the results unbiased.

You will need to attend regular clinic visits at the hospital. During these visits, the research team will carry out standard health checks, including blood tests, physical examinations, and skin evaluations. You will also be asked to complete questionnaires about your symptoms, everyday activities, and overall quality of life. Travel expenses are often supported by the study team.