(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

Phase 3RecruitingNCT04910685

Blueprint Medicines Corporation534 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

534

Conditions

Indolent Systemic Mastocytosis Smoldering Systemic Mastocytosis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: All Participants: -Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2. Part 1 and PK groups: * 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. 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 biopsy 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: * 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 * Participant has a QT interval corrected using Fridericia's formula (QTcF) \> \> 470 milliseconds (msec) (for females) or \> 450 msec (for males). * Participant has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. * Time since any cytoreductive therapy including masitinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy \< 28 days or 5 half-lives of the drug (whichever is longer), before beginning the screening period. * Participant has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy \< 14 days before beginning the screening period. Other protocol-defined criteria apply.

Locations (54)

University of Alabama at Birmingham

Birmingham, Alabama, United States

RECRUITING

Stanford Cancer Institute

Palo Alto, California, United States

RECRUITING

UCHealth Blood Disorders and Cell Therapies Center - Anschutz Medical Campus

Aurora, Colorado, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis

Overview

Conditions

Interventions

Eligibility

Locations (54)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts