What is the mechanism of action of this treatment?

Common treatments for Mast Cell Activation Syndrome (MCAS) often target the stabilization and inhibition of mast cells to prevent the release of inflammatory mediators. Masitinib, a Tyrosine Kinase Inhibitor, works by inhibiting the activity of mast cells, thereby reducing symptoms such as inflammation, allergic reactions, and gastrointestinal issues. Other treatments include antihistamines, which block histamine receptors to alleviate allergic symptoms, and leukotriene inhibitors, which prevent the action of leukotrienes involved in inflammatory responses. These mechanisms are crucial for MCAS patients as they help manage chronic symptoms and improve quality of life by reducing the frequency and severity of mast cell activation episodes.

What side effects are associated with this type of intervention?

Common treatments for Mast Cell Activation Syndrome (MCAS) include tyrosine kinase inhibitors like masitinib, antihistamines, and corticosteroids. Tyrosine kinase inhibitors, such as masitinib, can cause side effects including gastrointestinal issues (nausea, vomiting, diarrhea), skin reactions (rash, itching), and hematologic abnormalities (anemia, neutropenia). Antihistamines may lead to drowsiness, dry mouth, and dizziness, while corticosteroids can cause weight gain, hypertension, and increased risk of infections. It is important to discuss these potential side effects with a healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Mast Cell Activation Syndrome (MCAS) that are directly comparable to Masitinib, a tyrosine kinase inhibitor. However, treatments for conditions involving mast cell activity often include antihistamines, mast cell stabilizers like cromolyn sodium, and leukotriene inhibitors. These treatments aim to manage symptoms by reducing mast cell degranulation and the release of mediators.

What other types of research exist?

Promising novel alternatives to Masitinib for treating Mast Cell Activation Syndrome (MCAS) in 2024 may include therapies targeting interleukins such as Ustekinumab (targets IL-12 and IL-23) and other immune-modulating treatments like Vedolizumab (targets alpha4beta7 integrin). These therapies are used in related immune-mediated conditions and may offer potential benefits for MCAS patients.

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Tyrosine Kinase Inhibitor

Masitinib for Severe Mast Cell Activation Syndrome

Phase 2

Recruiting

Led By Julien Rossignol, MD

Research Sponsored by AB Science

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patient with severe symptoms over the 14-day run-in period defined as at least one of the following: Pruritus score ≥ 9; Number of flushes per week ≥ 8; Hamilton rating scale for depression (HAMD-17) score ≥ 19.

Patient with documented treatment failures of his/her handicap(s) (within last two years) with at least two of the symptomatic treatments used at optimized dose.

Must not have

Patient with systemic indolent mastocytosis.

Previous treatment with any Tyrosine Kinase Inhibitor.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 8 to week 24

Summary

This trial tests if masitinib, a pill, can help people with severe MCAS who haven't improved with other treatments. It works by calming down cells that cause allergic reactions and inflammation.

Who is the study for?

This trial is for patients with severe Mast Cell Activation Syndrome (MCAS) who haven't responded to other treatments. They must have had significant symptoms like intense itching, frequent flushes, or depression during a two-week period and failed at least two optimized dose treatments in the past two years. Participants should be on a stable anti-histamine regimen and not pregnant or breastfeeding.

What is being tested?

The trial tests how effective and safe different doses of oral masitinib are compared to a placebo in treating severe MCAS unresponsive to optimal symptomatic treatment. Patients will receive either masitinib at 4.5 mg/kg/day, masitinib at 6.0 mg/kg/day, placebo, or best supportive care.

What are the potential side effects?

Masitinib may cause side effects such as nausea, vomiting, diarrhea, rash, fatigue and edema. It can also affect blood counts leading to anemia or increase the risk of infections due to weakened immune responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have severe itching, frequent hot flashes, or significant depression.

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I've tried at least two treatments for my condition without success in the last two years.

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I have been diagnosed with mast cell activation syndrome.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a slow-growing form of mastocytosis affecting my whole body.

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I have been treated with a Tyrosine Kinase Inhibitor before.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 8 to week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 8 to week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 8 to week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Confirmed response at 50%

Secondary study objectives

Confirmed response (75%)

Cumulative response

Patient-Reported Outcome for Symptom Severity (PROSS)

Side effects data

From 2009 Phase 3 trial • 463 Patients • NCT00113763

66%

ERYTHEMA

58%

PRURITUS

57%

DERMATITIS ACNEIFORM

28%

ANOREXIA

26%

FATIGUE

25%

PARONYCHIA

24%

ABDOMINAL PAIN

22%

RASH

22%

NAUSEA

21%

DIARRHOEA

20%

SKIN FISSURES

19%

CONSTIPATION

18%

EXFOLIATIVE RASH

18%

VOMITING

16%

PYREXIA

16%

DYSPNOEA

15%

COUGH

14%

ACNE

13%

COLORECTAL CANCER METASTATIC

12%

OEDEMA PERIPHERAL

12%

ASTHENIA

10%

BACK PAIN

10%

NAIL DISORDER

10%

DRY SKIN

SKIN EXFOLIATION

ABDOMINAL PAIN UPPER

INSOMNIA

COLORECTAL CANCER

STOMATITIS

SKIN ULCER

GENERAL PHYSICAL HEALTH DETERIORATION

GROWTH OF EYELASHES

MUCOSAL INFLAMMATION

JAUNDICE

ANXIETY

HEPATOMEGALY

WEIGHT DECREASED

INTESTINAL OBSTRUCTION

ANAEMIA

ASCITES

HEPATIC FAILURE

DEHYDRATION

COMA

GASTROINTESTINAL OBSTRUCTION

RECTAL HAEMORRHAGE

HYPERBILIRUBINAEMIA

CACHEXIA

METASTASES TO LIVER

METASTASES TO LUNG

HEMIPARESIS

EPILEPSY

DEPRESSED LEVEL OF CONSCIOUSNESS

HEPATIC ENCEPHALOPATHY

PULMONARY EMBOLISM

DEEP VEIN THROMBOSIS

JUGULAR VEIN THROMBOSIS

100%

80%

60%

40%

20%

Study treatment Arm

Panitumumab Plus BSC

BSC Alone

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Masitinib (6.0) & BSCExperimental Treatment2 Interventions

Masitinib 6.0 mg/kg/day administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for4 weeks of treatment, then a second dose escalation to 6 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control.

Group II: Masitinib (4.5) & BSCExperimental Treatment2 Interventions

Masitinib 4.5 mg/kg/day administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive masitinib (3.0 mg/kg/day) for 4 weeks, given orally twice daily, with a dose escalation to 4.5 mg/kg/day for the remainder of the treatment period. Each ascending dose titration is subjected to a safety control.

Group III: Placebo & BSCPlacebo Group2 Interventions

Placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC). Participants receive a matched dose placebo, given orally twice daily.

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Mast Cell Activation Syndrome (MCAS) often target the stabilization and inhibition of mast cells to prevent the release of inflammatory mediators. Masitinib, a Tyrosine Kinase Inhibitor, works by inhibiting the activity of mast cells, thereby reducing symptoms such as inflammation, allergic reactions, and gastrointestinal issues. Other treatments include antihistamines, which block histamine receptors to alleviate allergic symptoms, and leukotriene inhibitors, which prevent the action of leukotrienes involved in inflammatory responses. These mechanisms are crucial for MCAS patients as they help manage chronic symptoms and improve quality of life by reducing the frequency and severity of mast cell activation episodes.

Efficacy and Safety of Masitinib in Progressive Forms of Multiple Sclerosis: A Randomized, Phase 3, Clinical Trial.Ruxolitinib improves symptoms and quality of life in a patient with systemic mastocytosis.Risk of mucocutaneous toxicities in patients with solid tumors treated with lapatinib: a systematic review and meta-analysis.