This is a Phase 2, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of avapritinib + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) and smoldering systemic mastocytosis (SSM) whose symptoms are not adequately controlled by BSC. The study will be conducted in 3 parts. All patients will receive treatment with avapritinib during Part 3 including those rolling over from the placebo group.
Name: Avapritinib
Description: Avapritinib tabletType: Drug(Part 1) Avapritinib Dose 1 + BSC (Part 1) Avapritinib Dose 2 + BSC (Part 1) Avapritinib Dose 3 + BSC (Part 2) Avapritinib RP2D + BSC (Part 3) Avapritinib RP2D + BSC
Name: Placebo
Description: Placebo tabletType: Drug(Part 1) Placebo + BSC (Part 2) Placebo + BSC
Description: 0 - 120 points (higher value represents worse symptom outcomes)
Measure: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) in patients with ISM and SSM (Part 2) Time: 12 weeksDescription: 0 - 120 points (higher value represents worse symptom outcomes)
Measure: Mean change in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) in patients with ISM and SSM (long term, Part 3) Time: Up to 5 yearsDescription: CTCAE version 5.0
Measure: Safety of avapritinib as assessed by number of adverse events (long term, Part 3) Time: Up to 5 yearsDescription: 0 - 100 points (higher value represents worse symptom outcomes)
Measure: Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) Time: Each study visit through Part 3 Week 52Description: 0 - 10 points (higher value represents worse symptom outcomes)
Measure: Change in Patient's Global Impression of Symptom Severity (PGIS) Time: Each study visit through Part 3 Week 52Description: 0 - 100 points (higher value represents better symptom outcomes)
Measure: Change in 12-item Short Form Health Survey (SF-12) Time: Each study visit through Part 3 Week 52Description: 1 - 7 (higher value represents worse symptom outcomes)
Measure: Change in Patients' Global Impression of Change (PGIC) Time: Each study visit through Part 3 Week 52Description: 0 - 100 (higher value represents better symptom outcomes)
Measure: Change in EuroQuol 5 Dimensions 5 Levels (EQ 5D-5L) Time: Each study visit through Part 3 Week 52Description: CTCAE version 5.0
Measure: Safety of avapritinib as assessed by number of adverse events Time: Up to 5 yearsDescription: h•ng/mL
Measure: Area Under Curve (0 to Tau) for avapritinib (Parts 1 and 2 only) Time: Every cycle (28 days) up to cycle 4Allocation: Randomized
Parallel Assignment
There is one SNP
Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood. --- D816V ---