Back to resultsMasitinib for the Treatment of Severe Mast Cell Activation Syndrome
Primary Purpose
Mast Cell Activation Syndrome
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Masitinib 4.5 mg/kg/day
Placebo
Best supportive care
Masitinib 6.0 mg/kg/day
Sponsored by
About this trial
This is an interventional treatment trial for Mast Cell Activation Syndrome
Eligibility Criteria
Inclusion Criteria include:
- Patient with mast cell activation syndrome (MCAS).
- 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.
- Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period.
Exclusion Criteria include:
- Previous treatment with any Tyrosine Kinase Inhibitor.
- Any change in the symptomatic treatment of MCAS, including systemic corticosteroids, or administration of any new treatment for MCAS within 4 weeks prior to screening.
- Patient with systemic indolent mastocytosis.
- Female patients who are pregnant or are breastfeeding.
Sites / Locations
- St Charles Clinical ResearchRecruiting
- Centre Hospitalier Universitaire Amiens-PicardieRecruiting
- Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)Recruiting
- CHU ToulouseRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Masitinib (4.5) & BSC
Masitinib (6.0) & BSC
Placebo & BSC
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Confirmed response at 50%
Confirmed response at 50%, defined as an improvement with respect to the baseline values of 50% for Pruritus, Flushes and Depression (HAMD-17 score) which should be confirmed from the previous visit.
Handicaps at baseline defined as: pruritus score ≥ 9; number of flushes per week ≥ 8; HAMD-17 score ≥ 19.
Secondary Outcome Measures
Cumulative response
Cumulative (every patient visit) response at 75% on 3 handicaps (pruritus, flush, depression) from week 8 to week 24. Analysis will be performed using Generalized Estimating Equations (GEE) model with stratification.
Confirmed response (75%)
Confirmed response at 75%, defined as an an improvement with respect to the baseline values of 75% for Pruritus, Flushes and Depression (Hamilton Depression Rating Scale) which should be confirmed from the previous visit. The Hamilton Depression Rating Scale (HAMD-17) has 17 items and is scored between 0 and 4 points. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52.
Patient-Reported Outcome for Symptom Severity (PROSS)
Changes in MCAS symptom severity will also be assessed using the Patient-Reported Outcome for Symptom Severity (PROSS) questionnaire. Total and individual symptom scores will be determined at baseline and at every visit until Week 24.The PROSS questionnaire has 11 items and is scored between 0 and 10 points. A score of 0 is an absence of the symptom and a score of 10 is very severe; the maximum score being 110.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05449444
Brief Title
Masitinib for the Treatment of Severe Mast Cell Activation Syndrome
Official Title
A 24-week, Multicenter, Randomized, Double Blind, Placebo-controlled, Dose-range Finding Phase II Study to Compare Efficacy and Safety of Oral Masitinib to Placebo in Treatment of Patients With Severe Mast Cell Activation Syndrome (MCAS) With Handicap Unresponsive to Optimal Symptomatic Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AB Science
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To evaluate the efficacy and safety of two dosing schemes of oral masitinib versus matching placebo in the treatment of patients suffering from severe MCAS with handicap unresponsive to optimal symptomatic treatment.
Detailed Description
Multicenter, double-blind, placebo-controlled trial comparing two different dosing schemes over a 24-week treatment period.
Dosing scheme #1: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for the remainder of the treatment period, versus placebo with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS).
Dosing scheme #2: Oral masitinib treatment at 3 mg/kg/day for 4 weeks, then a switch to 4.5 mg/kg/day for 4 weeks, then a second switch to 6 mg/kg/day for the remainder of the treatment period versus placebo treatment with a matching titration scheme. Randomization 2: 1 (Masitinib MCAS: Placebo MCAS)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mast Cell Activation Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
Masking
ParticipantInvestigator
Masking Description
Eligible patients will be randomized by means of a computerized central randomization system called IWRS (interactive web response system).
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Masitinib (4.5) & BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
Masitinib (6.0) & BSC
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo & BSC
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Masitinib 4.5 mg/kg/day
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib 4.5 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Matching placebo
Intervention Type
Other
Intervention Name(s)
Best supportive care
Other Intervention Name(s)
BSC
Intervention Description
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, sodium cromoglicate, antidepressants, antileukotrienes, proton pump inhibitors, and corticosteroids.
Intervention Type
Drug
Intervention Name(s)
Masitinib 6.0 mg/kg/day
Other Intervention Name(s)
AB1010
Intervention Description
Masitinib 6.0 mg/kg/day
Primary Outcome Measure Information:
Title
Confirmed response at 50%
Description
Confirmed response at 50%, defined as an improvement with respect to the baseline values of 50% for Pruritus, Flushes and Depression (HAMD-17 score) which should be confirmed from the previous visit.
Handicaps at baseline defined as: pruritus score ≥ 9; number of flushes per week ≥ 8; HAMD-17 score ≥ 19.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Cumulative response
Description
Cumulative (every patient visit) response at 75% on 3 handicaps (pruritus, flush, depression) from week 8 to week 24. Analysis will be performed using Generalized Estimating Equations (GEE) model with stratification.
Time Frame
week 8 to week 24
Title
Confirmed response (75%)
Description
Confirmed response at 75%, defined as an an improvement with respect to the baseline values of 75% for Pruritus, Flushes and Depression (Hamilton Depression Rating Scale) which should be confirmed from the previous visit. The Hamilton Depression Rating Scale (HAMD-17) has 17 items and is scored between 0 and 4 points. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score being 52.
Time Frame
24 weeks
Title
Patient-Reported Outcome for Symptom Severity (PROSS)
Description
Changes in MCAS symptom severity will also be assessed using the Patient-Reported Outcome for Symptom Severity (PROSS) questionnaire. Total and individual symptom scores will be determined at baseline and at every visit until Week 24.The PROSS questionnaire has 11 items and is scored between 0 and 10 points. A score of 0 is an absence of the symptom and a score of 10 is very severe; the maximum score being 110.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria include:
Patient with mast cell activation syndrome (MCAS).
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.
Patients must be on a stable dose of Anti-H1 for a minimum of 4 weeks before screening and should remain at a stable dose throughout the study period.
Exclusion Criteria include:
Previous treatment with any Tyrosine Kinase Inhibitor.
Any change in the symptomatic treatment of MCAS, including systemic corticosteroids, or administration of any new treatment for MCAS within 4 weeks prior to screening.
Patient with systemic indolent mastocytosis.
Female patients who are pregnant or are breastfeeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Study Coordinator
Phone
+33(0)147200014
Email
clinical@ab-science.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien Rossignol, MD
Organizational Affiliation
Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Charles Clinical Research
City
Weldon Spring
State/Province
Missouri
ZIP/Postal Code
63304
Country
United States
Individual Site Status
Recruiting
Facility Name
Centre Hospitalier Universitaire Amiens-Picardie
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Name
Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Toulouse
City
Toulouse
Country
France
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
No Masitinib is under clinical investigation and has not yet been approved in any sought-after indication by any health authority worldwide. As such, there is no plan for data-sharing at this point in time.
Citations:
PubMed Identifier
28069279
Citation
Lortholary O, Chandesris MO, Bulai Livideanu C, Paul C, Guillet G, Jassem E, Niedoszytko M, Barete S, Verstovsek S, Grattan C, Damaj G, Canioni D, Fraitag S, Lhermitte L, Georgin Lavialle S, Frenzel L, Afrin LB, Hanssens K, Agopian J, Gaillard R, Kinet JP, Auclair C, Mansfield C, Moussy A, Dubreuil P, Hermine O. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017 Feb 11;389(10069):612-620. doi: 10.1016/S0140-6736(16)31403-9. Epub 2017 Jan 7.
Results Reference
background
PubMed Identifier
36048877
Citation
Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1.
Results Reference
derived
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Masitinib for the Treatment of Severe Mast Cell Activation Syndrome
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