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) 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
Name: Placebo
Description: 0 - 120 points (higher value represents worse symptom outcomes)
Measure: Part 2: Proportion of responders, defined as ≥30% reduction in ISM Symptom Assessment Form (ISM-SAF) total symptom score (TSS) Time: 6 monthsDescription: 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 Cycle 12 (28-day cycles)Description: 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 Cycle 12 (28-day cycles)Description: 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 Cycle 12 (28-day cycles)Description: 1 - 7 (higher value represents worse symptom outcomes)
Measure: Change in Patients' Global Impression of Change (PGIC) Time: Each study visit through Part 3 Cycle 12 (28-day cycles)Description: 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 Cycle 12 (28-day cycles)Description: CTCAE version 5.0
Measure: Safety of avapritinib as assessed by number of adverse events Time: Up to 5 yearsDescription: h•ng/mL
Measure: Part 1 and Part 2 only: Area Under Curve (0 to Tau) for avapritinib Time: Every cycle (28 days) up to Cycle 4 (Part 1) and Cycle 7 (Part 2)Allocation: Randomized
Parallel Assignment
There is one SNP
Part 2: Proportion of patients with a ≥50% reduction in peripheral blood V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele fraction or undetectable for patients with detectable mutation at Baseline. --- D816V ---
Change in V-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog aspartate 816 valine (KIT D816V) allele burden in blood. --- D816V ---