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NCT Number: NCT04910685

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

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.

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Key information

Conditions

Indolent Systemic Mastocytosis Immune System Diseases Mast Cell Activation Disorders Mastocytosis Mastocytosis, Systemic Neoplasms Neoplasms by Histologic Type Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue Smoldering Systemic Mastocytosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

CHP Centro Hematologico Pavlovsky, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Elenestinib

Drug

Elenestinib oral tablet

Other names: BLU-263

Placebo

Drug

Placebo oral tablet

Primary outcomes

  1. Part 1: Number of participants with Treatment-emergent Adverse Events (TEAEs)

    Time frame: Up to 12 weeks

  2. Part 1: Mean change from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)

    Time frame: Baseline, Week 13

  3. Part 2: Mean change from baseline in ISM-SAF TSS

    Time frame: Baseline, Week 49

  4. Part 3: Number of participants with Adverse Events (AEs)

    Time frame: Up to 5 years

  5. Part 3: Change from baseline in ISM-SAF TSS

    Time frame: Baseline up to 5 years

Secondary outcomes

  1. Part 1: Change from baseline in serum tryptase

    Time frame: Baseline, Week 13

  2. Part 1: Change from baseline in KIT D816V allele fraction in blood

    Time frame: Baseline, Week 13

  3. Part 1: Change from baseline in Bone Marrow (BM) mast cells

    Time frame: Baseline, Week 13

  4. Part 1: Mean change from baseline in ISM-SAF individual symptom scores

    Time frame: Baseline, Week 13

  5. Part 1: Time to achieve 30% reduction from baseline in ISM-SAF TSS

    Time frame: Baseline up to Week 13

  6. Part 1: Time to achieve 30% reduction from baseline in ISM-SAF domain scores

    Time frame: Baseline up to Week 13

  7. Part 2: Proportion of participants achieving normalized tryptase

    Time frame: Baseline up to Week 49

  8. 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

  9. Part 2: Proportion of participants achieving symptom control as defined by achieving mild symptoms

    Time frame: Baseline up to Week 49

  10. Part 2: Mean percent change from baseline in Bone Mineral Density (BMD)

    Time frame: Baseline, Week 49

  11. Part 2: Mean change from baseline in the annualized rate of anaphylaxis events

    Time frame: Baseline, Weeks 25 to 48

  12. Part 2: Mean change from baseline in Quality of Life (QoL) scores

    Time frame: Baseline, Week 49

  13. Part 2: Mean change from baseline in ISM-SAF domain scores

    Time frame: Baseline, Week 49

  14. Part 2: Number of participants with AEs

    Time frame: Up to Week 49

  15. Part 2: Proportion of participants with a 50% reduction in ISM-SAF TSS

    Time frame: Baseline, Weeks 24 and 48

  16. Part 2: Proportion of participants with a 50% reduction in ISM-SAF domain scores

    Time frame: Baseline, Weeks 24 and 48

  17. Part 2: Proportion of participants with a 30% reduction in ISM-SAF TSS

    Time frame: Baseline, Weeks 24 and 48

  18. Part 2: Proportion of participants with a 30% reduction in ISM-SAF domain scores

    Time frame: Baseline, Weeks 24 and 48

  19. Part 3: Proportion of participants achieving symptom control as defined by achieving mild symptoms

    Time frame: Baseline up to 5 years

  20. Part 3: Change from baseline in ISM-SAF domain scores

    Time frame: Baseline, up to 5 years

  21. Part 3: Proportion of participants achieving a normalized tryptase

    Time frame: Baseline up to 5 years

  22. Part 3: Change from baseline in BMD

    Time frame: Baseline up to 5 years

  23. Part 3: Change from baseline in the annualized rate of anaphylaxis events

    Time frame: Baseline up to 5 years

  24. Parts 2 and 3: Change from baseline in serum tryptase

    Time frame: Baseline up to 5 years

  25. Parts 2 and 3: Change from baseline in KIT D816V allele fraction in blood

    Time frame: Baseline up to 5 years

  26. Parts 2 and 3: Change from baseline in Bone Marrow (BM) mast cells

    Time frame: Baseline up to 5 years

  27. Parts 2 and 3: Proportion of participants achieving controlled disease

    Time frame: Baseline up to 5 years

  28. 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

  29. Parts 2 and 3: Change from baseline in the number of concomitant medications identified as SDT

    Time frame: Baseline up to 5 years

  30. Parts 2 and 3: Change from baseline in ISM-SAF Individual Symptom Scores

    Time frame: Baseline up to 5 years

  31. Parts 2 and 3: Change from baseline in ISM-SAF Lead (most severe) Symptom Score

    Time frame: Baseline up to 5 years

  32. Parts 2 and 3: Change from baseline in QoL scores

    Time frame: Baseline up to 5 years

  33. Part S: Number of participants with AEs

    Time frame: Baseline up to 5 years

  34. Part S: Proportion of participants who achieve a Pure Pathologic Response (PPR)

    Time frame: Baseline up to 5 years

  35. Part S: Mean change from baseline in ISM-SAF

    Time frame: Baseline, Week 25

  36. Part K: Number of participants with AEs

    Time frame: Baseline up to 5 years

  37. Part K: Change from baseline in serum tryptase

    Time frame: Baseline up to 5 years

  38. Part K: Change from baseline in KIT D816V allele fraction in blood

    Time frame: Baseline up to 5 years

  39. Part K: Mean change from baseline in ISM-SAF TSS

    Time frame: Baseline up to 5 years

  40. Part K: Change from baseline in QoL scores

    Time frame: Baseline up to 5 years

Study contacts

Contact information is provided by the study sponsor or research team.

Blueprint Medicines

CONTACT

[email protected]

617-714-6707

Sponsors and collaborators

Lead sponsor

Blueprint Medicines Corporation

Industry

Registry information

Official study title

A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis

Important dates

Study start
2021
Primary completion
2032
Study completion
2032
First posted
Jun 2, 2021
Registry last updated
Jun 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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