Mast Cell Activation SyndromePhase 2NCT05449444
Masitinib for the Treatment of Severe Mast Cell Activation Syndrome
A Phase 2 study testing Masitinib 4.5 mg/kg/day and Masitinib 6.0 mg/kg/day in people with Mast Cell Activation Syndrome, run by AB Science at 4 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Mast Cell Activation Syndrome
- What is being tested?
- Masitinib 4.5 mg/kg/day and Masitinib 6.0 mg/kg/day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 1 Jul 2022to 31 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Universitaire Amiens-Picardie
Amiens
- Recruiting
Necker-Enfants Malades Hospital, Centre de référence des Mastocytoses (CEREMAST)
Paris
- Recruiting
CHU Toulouse
Toulouse
United States1 site, 1 recruiting
- Recruiting
St Charles Clinical Research
Weldon Spring, Missouri, 63304
About this study
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
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.
Read the 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)
- Conditions
- Mast Cell Activation Syndrome
- Being tested
- Masitinib 4.5 mg/kg/day, Placebo, Best supportive care, Masitinib 6.0 mg/kg/day
- Medical subject headings
- Mast Cell Activation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Masitinib 4.5 mg/kg/dayDrug
Also called AB1010
Masitinib 4.5 mg/kg/day
PlaceboDrug
Also called Placebo Oral Tablet
Matching placebo
Best supportive careOther
Also called BSC
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, sodium cromoglicate, antidepressants, antileukotrienes, proton pump inhibitors, and corticosteroids.
Masitinib 6.0 mg/kg/dayDrug
Also called AB1010
Masitinib 6.0 mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| Masitinib (4.5) & BSC | Experimental | 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. Receives: Drug: Masitinib 4.5 mg/kg/day; Other: Best supportive care |
| Masitinib (6.0) & BSC | Experimental | 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. Receives: Other: Best supportive care; Drug: Masitinib 6.0 mg/kg/day |
| Placebo & BSC | Placebo comparator | 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. Receives: Drug: Placebo; Other: Best supportive care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (3)
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.
Measured: week 8 to week 24
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.
Measured: 24 weeks
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2022
- Study start1 Jul 2022
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mast Cell Activation SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AB Science
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julien Rossignol, MD, Principal investigator, Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05449444
- Sponsor's protocol ID
- AB20006
- Other IDs
- 2021-005406-96
- Status last verified
- Feb 2023
- First submitted
- 2 Jul 2022
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Publications
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.
PubMed 28069279Latham 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.
PubMed 36048877
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05449444
- Acronym / sponsor ID
- AB20006
- Conditions
- Mast Cell Activation Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- AB ScienceIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2022 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 8 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Randomized, double-blind, placebo-controlled, parallel-group, multicenter comparative study with ascending dose titrations of masitinib and matching placebo
| Arm | Type | Receives |
|---|---|---|
| Masitinib (4.5) & BSC | Experimental | Drug: Masitinib 4.5 mg/kg/day, Other: Best supportive careMasitinib 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) & BSC | Experimental | Other: Best supportive care, Drug: Masitinib 6.0 mg/kg/dayMasitinib 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 & BSC | Placebo comparator | Drug: Placebo, Other: Best supportive carePlacebo 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Masitinib 4.5 mg/kg/dayAlso: AB1010Masitinib 4.5 mg/kg/day | Drug | Masitinib (4.5) & BSC |
| PlaceboAlso: Placebo Oral TabletMatching placebo | Drug | Placebo & BSC |
| Best supportive careAlso: BSCOptimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, sodium cromoglicate, antidepressants, antileukotrienes, proton pump inhibitors, and corticosteroids. | Other | Masitinib (4.5) & BSC, Masitinib (6.0) & BSC, Placebo & BSC |
| Masitinib 6.0 mg/kg/dayAlso: AB1010Masitinib 6.0 mg/kg/day | Drug | Masitinib (6.0) & BSC |
Primary outcome
Confirmed response at 50%
Time frame: 24 weeks
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.
3 secondary outcomes
Cumulative response
Time frame: week 8 to week 24
Confirmed response (75%)
Time frame: 24 weeks
Patient-Reported Outcome for Symptom Severity (PROSS)
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Background: PubMed 28069279Lortholary 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.
- Derived from this study: PubMed 36048877Latham 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.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien Rossignol, MD principal investigator
Reference Centre for Mastocytosis (CEREMAST), Necker Hospital, Paris, France
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Masitinib 4.5 mg/kg/day and Masitinib 6.0 mg/kg/day in people with Mast Cell Activation Syndrome, run by AB Science at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Clinical Study Coordinator (+33(0)147200014, clinical@ab-science.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed response at 50% (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05449444, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.