A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 534
- 试验地点
- 110
- 主要终点
- Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All Participants:
- •Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to
- •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.
- •Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
- •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.
- •Participant has confirmed diagnosis of ISM, confirmed by Central Pathology Review
排除标准
- •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.
研究组 & 干预措施
(Part 2) Placebo + SDT
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.
干预措施: Placebo (Drug)
(Part 1) Placebo + SDT
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.
干预措施: Placebo (Drug)
(Part 1) Elenestinib Dose 1 + SDT
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.
干预措施: Elenestinib (Drug)
(Part S) Elenestinib Dose 1 + SDT
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.
干预措施: Elenestinib (Drug)
(Part 3) Elenestinib + SDT
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.
干预措施: Elenestinib (Drug)
(Part 2) Elenestinib Dose 1 + SDT
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.
干预措施: Elenestinib (Drug)
(Part 1) Elenestinib Dose 3 + SDT
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.
干预措施: Elenestinib (Drug)
(Part 1) Elenestinib Dose 2 + SDT
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.
干预措施: Elenestinib (Drug)
(Part K) Elenestinib Dose 1 + SDT
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.
干预措施: Elenestinib (Drug)
(PK groups) Elenestinib + SDT
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.
干预措施: Elenestinib (Drug)
结局指标
主要结局
Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 12 weeks
Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
时间窗: Baseline, Week 13
Part 2: Mean change from baseline in ISM-SAF TSS
时间窗: Baseline, Week 49
Part 3: Number of participants with Adverse Events (AEs)
时间窗: Up to 5 years
Part 3: Change from baseline in ISM-SAF TSS
时间窗: Baseline up to 5 years
次要结局
- Part 1: Change from baseline in serum tryptase(Baseline, Week 13)
- Part 1: Change from baseline in KIT D816V allele fraction in blood(Baseline, Week 13)
- Part 1: Change from baseline in Bone Marrow (BM) mast cells(Baseline, Week 13)
- Part 1: Mean change from baseline in ISM-SAF individual symptom scores(Baseline, Week 13)
- Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS(Baseline up to Week 13)
- Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores(Baseline up to Week 13)
- Part 2: Proportion of participants achieving normalized tryptase(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)(Baseline up to Week 49)
- Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms(Baseline up to Week 49)
- Part 2: Mean percent change from baseline in Bone Mineral Density (BMD)(Baseline, Week 49)
- Part 2: Mean change from baseline in the annualized rate of anaphylaxis events(Baseline, Weeks 25 to 48)
- Part 2: Mean change from baseline in Quality of Life (QoL) scores(Baseline, Week 49)
- Part 2: Mean change from baseline in ISM-SAF domain scores(Baseline, Week 49)
- Part 2: Number of participants with AEs(Up to Week 49)
- Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS(Baseline, Weeks 24 and 48)
- Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores(Baseline, Weeks 24 and 48)
- Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS(Baseline, Weeks 24 and 48)
- Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores(Baseline, Weeks 24 and 48)
- Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms(Baseline up to 5 years)
- Part 3: Change from baseline in ISM-SAF domain scores(Baseline, up to 5 years)
- Part 3: Proportion of participants achieving a normalized tryptase(Baseline up to 5 years)
- Part 3: Change from baseline in BMD(Baseline up to 5 years)
- Part 3: Change from baseline in the annualized rate of anaphylaxis events(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in serum tryptase(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells(Baseline up to 5 years)
- Parts 2 and 3: Proportion of participants achieving controlled disease(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(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score(Baseline up to 5 years)
- Parts 2 and 3: Change from baseline in QoL scores(Baseline up to 5 years)
- Part S: Number of participants with AEs(Baseline up to 5 years)
- Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR)(Baseline up to 5 years)
- Part S: Mean change from baseline in ISM-SAF(Baseline, Week 25)
- Part K: Number of participants with AEs(Baseline up to 5 years)
- Part K: Change from baseline in serum tryptase(Baseline up to 5 years)
- Part K: Change from baseline in KIT D816V allele fraction in blood(Baseline up to 5 years)
- Part K: Mean change from baseline in ISM-SAF TSS(Baseline up to 5 years)
- Part K: Change from baseline in QoL scores(Baseline up to 5 years)