A Phase 2/3 interventional study of Elenestinib and Placebo in Indolent Systemic Mastocytosis and Smoldering Systemic Mastocytosis, sponsored by Blueprint Medicines Corporation. Recruiting at 88 sites in 25 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by Blueprint Medicines Corporation (part of Sanofi) · Phase 2/3, Interventional, and Treatment
This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + symptom directed therapy (SDT) with placebo + SDT in participants with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by SDT. Parts 1 and 2 will enroll participants with ISM. Participants enrolled in Part 2 will roll over onto Part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier Part. Part K will enroll participants with ISM who have previously received an approved selective KIT inhibitor. The study also includes pharmacokinetic (PK) groups that will enroll participants with ISM.
56 studies on the registry are indexed under Mastocytosis, Systemic; 16 are open to participants now.
This study's planned enrollment of 534 is above the median of 36 across 34 interventional studies indexed under Mastocytosis, Systemic.
Browse Mastocytosis, Systemic studies →Blueprint Medicines Corporation is the lead sponsor of 32 studies on the registry; 6 are open to participants now.
Of its 14 completed or terminated interventional studies of FDA-regulated products, 3 (21%) have results posted.
First submitted before Blueprint Medicines Corporation became part of Sanofi.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
All Participants:
-Participant must have an Performance Status (ECOG PS) of 0 to 2.
Part 1 and PK groups:
Part K:
-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
Part S:
-Participant has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM and central review of B- and C-findings by WHO diagnostic criteria.
Part 2:
-Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
Key Exclusion Criteria:
Other protocol-defined criteria apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.
Drug: Elenestinib
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.
Drug: Elenestinib
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily until completion of Part 1.
Drug: Elenestinib
Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily until completion of Part 1.
Drug: Placebo
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for approximately 48 weeks.
Drug: Elenestinib
Participants will receive SDT and matching placebo. SDT will be determined on a per participant basis. Placebo will be administered orally, once daily for approximately 48 weeks.
Drug: Placebo
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.
Drug: Elenestinib
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.
Drug: Elenestinib
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.
Drug: Elenestinib
Participants will receive SDT and elenestinib. SDT will be determined on a per participant basis. Elenestinib will be administered orally, once daily for up to approximately 5 years.
Drug: Elenestinib
Elenestinib oral tablet
Also known as: BLU-263
Placebo oral tablet
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to 12 weeks
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Time frame: Baseline, Week 13
Part 2: Mean change from baseline in ISM-SAF TSS
Time frame: Baseline, Week 49
Part 3: Number of participants with Adverse Events (AEs)
Time frame: Up to 5 years
Part 3: Change from baseline in ISM-SAF TSS
Time frame: Baseline up to 5 years
Part 1: Change from baseline in serum tryptase
Time frame: Baseline, Week 13
Part 1: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline, Week 13
Part 1: Change from baseline in Bone Marrow (BM) mast cells
Time frame: Baseline, Week 13
Part 1: Mean change from baseline in ISM-SAF individual symptom scores
Time frame: Baseline, Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS
Time frame: Baseline up to Week 13
Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores
Time frame: Baseline up to Week 13
Part 2: Proportion of participants achieving normalized tryptase
Time frame: Baseline up to Week 49
Part 2: Proportion of participants who achieve an undetectable level or at least a 50% reduction in KIT D816V Variant Allele Frequency (VAF)
Time frame: Baseline up to Week 49
Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Time frame: Baseline up to Week 49
Part 2: Mean percent change from baseline in Bone Mineral Density (BMD)
Time frame: Baseline, Week 49
Part 2: Mean change from baseline in the annualized rate of anaphylaxis events
Time frame: Baseline, Weeks 25 to 48
Part 2: Mean change from baseline in Quality of Life (QoL) scores
Time frame: Baseline, Week 49
Part 2: Mean change from baseline in ISM-SAF domain scores
Time frame: Baseline, Week 49
Part 2: Number of participants with AEs
Time frame: Up to Week 49
Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS
Time frame: Baseline, Weeks 24 and 48
Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores
Time frame: Baseline, Weeks 24 and 48
Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms
Time frame: Baseline up to 5 years
Part 3: Change from baseline in ISM-SAF domain scores
Time frame: Baseline, up to 5 years
Part 3: Proportion of participants achieving a normalized tryptase
Time frame: Baseline up to 5 years
Part 3: Change from baseline in BMD
Time frame: Baseline up to 5 years
Part 3: Change from baseline in the annualized rate of anaphylaxis events
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in serum tryptase
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells
Time frame: Baseline up to 5 years
Parts 2 and 3: Proportion of participants achieving controlled disease
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in skin lesions as assessed by the fractional body surface area of the most affected skin area
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score
Time frame: Baseline up to 5 years
Parts 2 and 3: Change from baseline in QoL scores
Time frame: Baseline up to 5 years
Part S: Number of participants with AEs
Time frame: Baseline up to 5 years
Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR)
Time frame: Baseline up to 5 years
Part S: Mean change from baseline in ISM-SAF
Time frame: Baseline, Week 25
Part K: Number of participants with AEs
Time frame: Baseline up to 5 years
Part K: Change from baseline in serum tryptase
Time frame: Baseline up to 5 years
Part K: Change from baseline in KIT D816V allele fraction in blood
Time frame: Baseline up to 5 years
Part K: Mean change from baseline in ISM-SAF TSS
Time frame: Baseline up to 5 years
Part K: Change from baseline in QoL scores
Time frame: Baseline up to 5 years
Plan to share: No
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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