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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04910685




Registration number
NCT04910685
Ethics application status
Date submitted
17/05/2021
Date registered
2/06/2021
Date last updated
1/07/2024

Titles & IDs
Public title
(HARBOR) Study to Evaluate Efficacy and Safety of BLU-263 Versus Placebo in Patients With Indolent Systemic Mastocytosis
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Phase 2/3 Study of BLU-263 in Indolent Systemic Mastocytosis
Secondary ID [1] 0 0
BLU-263-1201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Indolent Systemic Mastocytosis 0 0
Monoclonal Mast Cell Activation Syndrome 0 0
Smoldering Systemic Mastocytosis 0 0
Condition category
Condition code
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Elenestinib
Treatment: Drugs - Placebo

Experimental: (Part 1) Elenestinib Dose 1 + BSC - Patients will receive best supportive care (BSC) and Dose 1 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Experimental: (Part 1) Elenestinib Dose 2 + BSC - Patients will receive BSC and Dose 2 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Experimental: (Part 1) Elenestinib Dose 3 + BSC - Patients will receive BSC and Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily until completion of Part 1.

Placebo comparator: (Part 1) Placebo + BSC - Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily until completion of Part 1

Experimental: (Part 2) Elenestinib RD + BSC - Patients will receive BSC and the recommended dose (RD) of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for approximately 24 weeks

Placebo comparator: (Part 2) Placebo + BSC - Patients will receive BSC and matching placebo. BSC will be determined on a per patient basis. Placebo will be administered orally, once daily once daily for approximately 24 weeks

Experimental: (Part 3) Elenestinib RD + BSC - Patients will receive open-label BSC and the RD of elenestinib for up to approximately 4 years.

Experimental: (Part M) Elenestinib RD + BSC - Patients will receive BSC and the RD of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally, once daily for the duration of participation in the study.

Experimental: PK Groups (Dose 2 or Dose 3) - Patients will receive BSC and Dose 2 or Dose 3 of elenestinib. BSC will be determined on a per patient basis. Elenestinib will be administered orally for the duration of participation in the study.

Experimental: (Part S) Elenestinib + BSC - Participants with Smoldering Systemic Mastocytosis (SSM) will receive open-label BSC and elenestinib for up to approximately 4 years.


Treatment: Drugs: Elenestinib
Elenestinib oral tablet

Treatment: Drugs: Placebo
Placebo oral tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Parts 1 and 3: Number of participants with Adverse Events (AEs)
Timepoint [1] 0 0
Up to 4 years
Primary outcome [2] 0 0
Part 2: Objective Response Rate (ORR), defined as proportion of patients who achieve =30% reduction from baseline in ISM-Symptom in Assessment Form (ISM-SAF) Total Symptom Score (TSS)
Timepoint [2] 0 0
Baseline, Week 25
Primary outcome [3] 0 0
Parts 1 and 3: Mean change from baseline in ISM-SAF TSS
Timepoint [3] 0 0
Baseline up to 4 years
Secondary outcome [1] 0 0
Parts 1, 2, and 3: Mean change from baseline in measures of mast cell burden
Timepoint [1] 0 0
Baseline up to 4 years
Secondary outcome [2] 0 0
Parts 1, 2, and 3: Mean change from baseline in ISM-SAF individual symptom scores
Timepoint [2] 0 0
Baseline up to 4 years
Secondary outcome [3] 0 0
Parts 1, 2, and 3: Time to achieve 30% reduction from baseline in ISM-SAF scores
Timepoint [3] 0 0
Baseline up to 4 years
Secondary outcome [4] 0 0
Part 2: Proportion of patients with a =50% reduction from baseline in serum tryptase
Timepoint [4] 0 0
Baseline, Week 25
Secondary outcome [5] 0 0
Part 2: Proportion of patients who achieve at least a 50% reduction in peripheral blood KIT D816V allele fraction, or a reduction to undetectable levels
Timepoint [5] 0 0
Baseline, Week 25
Secondary outcome [6] 0 0
Part 2: Mean change from baseline in ISM-SAF
Timepoint [6] 0 0
Baseline, Week 25
Secondary outcome [7] 0 0
Part 2: Proportion of patients with a =50% reduction in bone marrow mast cells or reduction to no aggregates for patients with aggregates at Baseline
Timepoint [7] 0 0
Baseline, Week 25
Secondary outcome [8] 0 0
Part 2: ORR
Timepoint [8] 0 0
Week 25
Secondary outcome [9] 0 0
Parts 2 and 3: Change form baseline in number of concomitant BSC medications
Timepoint [9] 0 0
Baseline up to 4 years
Secondary outcome [10] 0 0
Parts 2 and 3: Change from baseline in ISM-SAF leading symptom score
Timepoint [10] 0 0
Baseline up to 4 years
Secondary outcome [11] 0 0
Parts 2 and 3: Mean change from baseline in Quality of Life scores
Timepoint [11] 0 0
Baseline up to 4 years
Secondary outcome [12] 0 0
Part 2: Number of participants with AEs
Timepoint [12] 0 0
Up to Week 25
Secondary outcome [13] 0 0
Part S: Number of participants with AEs
Timepoint [13] 0 0
Baseline up to 4 years
Secondary outcome [14] 0 0
Part S: Proportion of participants who achieve a Complete Remission (CR)/Complete remission with partial recovery of peripheral blood counts (CRh), molecular CR/molecular CRh, or Partial Response (PR) based on Pure Pathologic Response (PPR) from Baseline
Timepoint [14] 0 0
Baseline up to 4 years
Secondary outcome [15] 0 0
Part S: Mean change in ISM-SAF from Baseline to after 24 weeks of treatment
Timepoint [15] 0 0
Week 25

Eligibility
Key inclusion criteria
Key

All Patients

-1. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2.

Part 1 and Part 2

* 2. Patient must have moderate-to-severe symptoms based on minimum mean total symptom score (TSS) of the ISM Symptom Assessment Form (ISM-SAF) over the 14-day eligibility screening period.
* 3. Patient has confirmed diagnosis of ISM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO diagnostic criteria. Archival biopsy may be used if completed within the past 12 months.
* 4. Patient 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 symptomatic therapies administered: H1 blockers, H2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab.
* 5. Patients must have BSC for ISM symptom management stabilized for at least 14 days prior to starting screening procedures.
* 6. For patients receiving corticosteroids, the dose must be = 20 mg/d prednisone or equivalent, and the dose must be stable for = 14 days.

Part M

* 7. Patients must have mMCAS, confirmed by Central Pathology Review of BM biopsy. An archival biopsy may be used if completed within the past 12 months.
* 8. Patients must have tryptase < 20 ng/mL.
* 9. Patients must have KIT D816V in peripheral blood (PB) or BM and/or CD25+ Mast cells in BM.
* 10. Patients must have symptoms consistent with mast cell activation (despite BSC) in at least two organ systems characterized by cutaneous flushing, tachycardia, syncope, hypotension, diarrhea, nausea, vomiting and gastro-intestinal cramping) and serum blood tryptase (sBT) levels above 8 ng/mL OR Severe (Ring and Messmer grading = II, recurrent anaphylaxis, including but not limited to hymenoptera venom, drug or food, regardless of sBT levels.

PK Groups

* 11. See inclusion criteria for All patients and Part 1/Part 2
* 12. Accrual may be limited to patients who have specific disease manifestations (ie, GI involvement) or are taking acid-reducing agents to better explore the impact of these features on PK.

Part S:

-13. Patient has confirmed diagnosis of SSM, confirmed by Central Pathology Review of BM biopsy and central review of B- and C-findings by WHO 2022 diagnostic criteria.

Key
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 1. Patient 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.
* 2. Patient has been diagnosed with another myeloproliferative disorder.
* 3. Patient has organ damage C-findings attributable to SM.
* 4. Patient has clinically significant, uncontrolled, cardiovascular disease
* 5. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
* 6. Patient has previously received treatment with any targeted KIT inhibitors.
* 7. Patient 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.
* 8. Time since any cytoreductive therapy including mastinib 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.
* 9.Patient has received radiotherapy or psoralen and ultraviolet A (PUVA) therapy < 14 days before beginning the screening period.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2028
Actual
Sample size
Target
463
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Woolloongabba
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
Austria
State/province [10] 0 0
Linz
Country [11] 0 0
Belgium
State/province [11] 0 0
Antwerpen
Country [12] 0 0
France
State/province [12] 0 0
Amiens
Country [13] 0 0
France
State/province [13] 0 0
Caen
Country [14] 0 0
France
State/province [14] 0 0
Grenoble Cedex 9
Country [15] 0 0
France
State/province [15] 0 0
Limoges Cedex
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Poitiers
Country [19] 0 0
France
State/province [19] 0 0
Toulouse
Country [20] 0 0
Germany
State/province [20] 0 0
Aachen
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Erlangen
Country [23] 0 0
Germany
State/province [23] 0 0
Hamburg
Country [24] 0 0
Germany
State/province [24] 0 0
Mannheim
Country [25] 0 0
Germany
State/province [25] 0 0
Munich
Country [26] 0 0
Italy
State/province [26] 0 0
Forli-Cesena
Country [27] 0 0
Italy
State/province [27] 0 0
Lombardia
Country [28] 0 0
Italy
State/province [28] 0 0
Toscana
Country [29] 0 0
Italy
State/province [29] 0 0
Bologna
Country [30] 0 0
Italy
State/province [30] 0 0
Pavia
Country [31] 0 0
Italy
State/province [31] 0 0
Salerno
Country [32] 0 0
Italy
State/province [32] 0 0
Verona
Country [33] 0 0
Netherlands
State/province [33] 0 0
Zuid-Holland
Country [34] 0 0
Netherlands
State/province [34] 0 0
Groningen
Country [35] 0 0
Norway
State/province [35] 0 0
Oslo
Country [36] 0 0
Portugal
State/province [36] 0 0
Lisbon
Country [37] 0 0
Portugal
State/province [37] 0 0
Porto
Country [38] 0 0
Spain
State/province [38] 0 0
Barcelona
Country [39] 0 0
Spain
State/province [39] 0 0
Madrid
Country [40] 0 0
Spain
State/province [40] 0 0
Toledo
Country [41] 0 0
Switzerland
State/province [41] 0 0
Basel
Country [42] 0 0
Switzerland
State/province [42] 0 0
Luzern
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Wales
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Blueprint Medicines Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled, Phase 2/3 study comparing the efficacy and safety of elenestinib (BLU-263) + best supportive care (BSC) with placebo + BSC in patients with indolent systemic mastocytosis (ISM) whose symptoms are not adequately controlled by BSC. Parts 1 and 2 will enroll patients with ISM. Patients enrolled in Part 1 or 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 M will enroll patients with monoclonal mast cell activation syndrome (mMCAS). Part S will enroll participants with smoldering systemic mastocytosis (SSM). The study also includes PK groups that will enroll patients with ISM.
Trial website
https://clinicaltrials.gov/study/NCT04910685
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Blueprint Medicines
Address 0 0
Country 0 0
Phone 0 0
617-714-6707
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04910685