Indolent Systemic MastocytosisPhase 3NCT04333108
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment
A Phase 3 study testing Masitinib in people with Indolent Systemic Mastocytosis, run by AB Science at 17 sites in 8 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Indolent Systemic Mastocytosis
- What is being tested?
- Masitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 17 sitesin 8 countries
- Study dates
- 1 Jul 2020to Jun 2025
- Phase
- Phase 3
- 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 one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
- An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
- Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
- Patient with documented treatment failure of his/her symptom(s) (within the past 2 years) with at least two of the symptomatic treatments used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium, Antileukotriene.
- Patient with severe symptoms of mastocytosis over the 14-day run-in period including at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.
Who cannot join
- Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
- Previous treatment with any Tyrosine Kinase Inhibitor
- Treatment with any investigational agent within 8 weeks prior to screening.
Trial locations and contacts
17 sites in 8 countries.
17 sites in 8 countries
France8 sites, 8 recruiting
- Recruiting
Centre Hospitalier Universitaire d'Amiens
Amiens
- Recruiting
Hospital Jean-Minjoz
Besançon
- Recruiting
Grenoble University Hospital
Grenoble
- Recruiting
Hospital Claude Huriez
Lille
- Recruiting
Marseille University Hospital Timone
Marseille
- Recruiting
Centre de référence de Mastocytose (CEREMAST)
Paris
- Recruiting
Poitiers University Hospital
Poitiers
- Recruiting
Centre Hospitalier Universitaire
Toulouse
Poland2 sites, 2 recruiting
- Recruiting
Medical University of Gdańsk
Gdansk
- Recruiting
The University Hospital in Krakow (Szpital Uniwersytecki w Krakowie)
Krakow
Ukraine2 sites, 2 recruiting
- Recruiting
Dnipropetrovsk Clinical Association of Emergency Medical Care of Dnipropetrovsk Regional
Dnipro
- Recruiting
Private Enterprise Private Manufacturing Company Acinus
Poltava
Germany1 site, 1 recruiting
- Not yet recruiting
University Hospital Charité
Berlin
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus University Medical Center
Rotterdam
Romania1 site, 1 recruiting
- Recruiting
University Hospital in Bucharest (Spitalul Universitar de Urgență București)
Bucharest
Russia1 site, 1 recruiting
- Recruiting
Almazov National Medical Research Centre
Saint Petersburg
United Kingdom1 site, 1 recruiting
- Recruiting
Guy's and St Thomas' NHS Foundation Trust
London
About this study
Official title: Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment
The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.
Read the detailed description
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
- Conditions
- Indolent Systemic Mastocytosis
- Being tested
- Masitinib, Placebo, Best Supportive Care
- Keywords
- Mastocytosis with handicap, Mastocytosis, Mast cell, Mast cell infiltration, Skin, Bone marrow, Pruritus, Flushes, c-kit, c-kit mutation, Wild Type, Mutation Asp-816-Val(D816V), Indolent systemic mastocytosis, smoldering systemic mastocytosis
- Medical subject headings
- Mastocytosis, Systemic, Mastocytosis, Pruritus, Blushing, Piebaldism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MasitinibDrug
Also called AB1010
Masitinib 6 mg/kg/day
PlaceboOther
Matching placebo
Best Supportive CareOther
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.
| Study group | Role | What they receive |
|---|---|---|
| Masitinib & BSC | Experimental | Experimental Arm:
Masitinib (titration to 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), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. Receives: Drug: Masitinib; Other: Best Supportive Care |
| Placebo & BSC | Placebo comparator | Placebo Comparator:
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC) Receives: Other: Placebo; Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative response (3R75%)
Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).
Measured: 24 weeks
Secondary outcomes (3)
Cumulative response (4R75%)
Cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response is defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).
Measured: 24 weeks
Cumulative response (2R75%)
Cumulative response in at least one of two severe baseline symptoms of mast cell mediator release (pruritus or flushes). Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 10 possible responses depending on the number of severe baseline symptoms).
Measured: 24 weeks
Cumulative response
Cumulative response on each of the individual handicaps. Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period.
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 posted3 Apr 2020
- Study start1 Jul 2020
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Indolent Systemic MastocytosisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AB Science
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Cristina Bulai Livideanu, MD, MSc, Principal investigator, Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04333108
- Sponsor's protocol ID
- AB15003
- Other IDs
- 2016-001447-39, 2016
- Status last verified
- May 2023
- First submitted
- 1 Apr 2020
- Last updated
- 6 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmerini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010 Dec;85(12):921-5. doi: 10.1002/ajh.21894.
PubMed 21108325Lortholary 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 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment
- ClinicalTrials.gov ID
- NCT04333108
- Acronym / sponsor ID
- AB15003
- Conditions
- Indolent Systemic Mastocytosis
- Keywords
- Mastocytosis with handicap, Mastocytosis, Mast cell, Mast cell infiltration, Skin, Bone marrow, Pruritus, Flushes
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- AB ScienceIndustry (pharma, biotech, devices)
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 3 Apr 2020 (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.
The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.
Detailed description
Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Masitinib & BSC | Experimental | Drug: Masitinib, Other: Best Supportive CareExperimental Arm: Masitinib (titration to 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), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control. |
| Placebo & BSC | Placebo comparator | Other: Placebo, Other: Best Supportive CarePlacebo Comparator: Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patient with one of the following documented mastocytosis subtypes (variants): Smouldering Systemic Mastocytosis, Indolent Systemic Mastocytosis
- An excess of mast cells or a presence of abnormal mast cells in at least two organs (among skin, bone-marrow and GI Tract).
- Patient with documented systemic mastocytosis and evaluable disease based upon histological criteria
- Patient with documented treatment failure of his/her symptom(s) (within the past 2 years) with at least two of the symptomatic treatments used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Antidepressants, Cromoglycate Sodium, Antileukotriene.
- Patient with severe symptoms of mastocytosis over the 14-day run-in period including at least one among pruritus, flushes, and depression: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19.
Key exclusion criteria (3 listed)
- Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
- Previous treatment with any Tyrosine Kinase Inhibitor
- Treatment with any investigational agent within 8 weeks prior to screening.
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 |
|---|---|---|
| MasitinibAlso: AB1010Masitinib 6 mg/kg/day | Drug | Masitinib & BSC |
| PlaceboMatching placebo | Other | Placebo & BSC |
| Best Supportive CareOptimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids. | Other | Masitinib & BSC, Placebo & BSC |
Primary outcome
Cumulative response (3R75%)
Time frame: 24 weeks
Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).
3 secondary outcomes
Cumulative response (4R75%)
Time frame: 24 weeks
Cumulative response (2R75%)
Time frame: 24 weeks
Cumulative response
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 May 2023.
- Background: PubMed 21108325Paul C, Sans B, Suarez F, Casassus P, Barete S, Lanternier F, Grandpeix-Guyodo C, Dubreuil P, Palmerini F, Mansfield CD, Gineste P, Moussy A, Hermine O, Lortholary O. Masitinib for the treatment of systemic and cutaneous mastocytosis with handicap: a phase 2a study. Am J Hematol. 2010 Dec;85(12):921-5. doi: 10.1002/ajh.21894.
- 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
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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.
Cristina Bulai Livideanu, MD, MSc principal investigator
Centre Hospitalier Universitaire, Service de Dermatologie, Toulouse -France
17 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Masitinib in people with Indolent Systemic Mastocytosis, run by AB Science at 17 sites in 8 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 5 inclusion and 3 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 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in France, Poland, Ukraine, Germany, Netherlands and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Cumulative response (3R75%) (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 NCT04333108, which also lists 3 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 May 2023.