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.
Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
Participant must have failed to achieve adequate symptom control for 1 or more Baseline symptoms, as determined by the Investigator, with at least 2 of the following symptom-directed therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
Participants must have SDT for ISM symptom management stabilized for at least 14 days prior to starting screening procedures.
For participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisone or equivalent, and the dose must be stable for ≥ 14 days.
Participant has been diagnosed with any of the following WHO systemic mastocytosis (SM) sub-classifications: cutaneous mastocytosis only, SM with an associated hematologic neoplasm of non-MC lineage (SM-AHN), aggressive SM, mast cell leukemia, or mast cell sarcoma.
Participant has been diagnosed with another myeloproliferative disorder.
Participant has organ damage attributable to SM.
Participant has clinically significant, uncontrolled, cardiovascular disease
Parallel
Elenestinib
DrugElenestinib oral tablet
Placebo
DrugPlacebo oral tablet
10
Treatment groupsSee each treatment group below.
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Part 2: Mean change from baseline in ISM-SAF TSS
Part 3: Number of participants with Adverse Events (AEs)
Part 1: Change from baseline in serum tryptase
Part 1: Change from baseline in KIT D816V allele fraction in blood
Part 1: Change from baseline in Bone Marrow (BM) mast cells
Part 1: Mean change from baseline in ISM-SAF individual symptom scores
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