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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05186753




Registration number
NCT05186753
Ethics application status
Date submitted
19/11/2021
Date registered
11/01/2022
Date last updated
7/11/2024

Titles & IDs
Public title
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
Scientific title
A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis
Secondary ID [1] 0 0
CGT9486-21-202
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
SSM 0 0
Mastocytosis, Indolent 0 0
Mastocytosis, Systemic 0 0
Mastocytosis 0 0
ISM 0 0
BMM 0 0
Smoldering Systemic Mastocytosis 0 0
Bone Marrow Mastocytosis 0 0
Condition category
Condition code
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bezuclastinib Tablets (Formulation A)
Treatment: Drugs - Bezuclastinib Tablets (Formulation B)
Treatment: Drugs - Placebo Tablets

Experimental: (Part 1a) Bezuclastinib Dose 1 + BSC -

Experimental: (Part 1a) Bezuclastinib Dose 2 + BSC -

Placebo comparator: (Part 1a) Placebo + BSC -

Experimental: (Part 1b) Bezuclastinib Dose 1 + BSC -

Experimental: (Part 1b) Bezuclastinib Dose 2 + BSC -

Placebo comparator: (Part 1b) Placebo + BSC -

Experimental: (Part 2) Bezuclastinib Selected Dose + BSC -

Placebo comparator: (Part 2) Placebo + BSC -

Experimental: (Part 3) Bezuclastinib + BSC -


Treatment: Drugs: Bezuclastinib Tablets (Formulation A)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Treatment: Drugs: Bezuclastinib Tablets (Formulation B)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Treatment: Drugs: Placebo Tablets
Placebo will be administered orally, once daily continuously for 28-day cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
Timepoint [1] 0 0
3 months
Primary outcome [2] 0 0
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
Timepoint [2] 0 0
24 Weeks
Primary outcome [3] 0 0
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [1] 0 0
Part 2: Proportion of subjects who had at least 50% reduction in serum tryptase
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Part 2: Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction
Timepoint [2] 0 0
24 weeks
Secondary outcome [3] 0 0
Part 2: Determine responder rates of subjects treated with bezuclastinib at the selected dose versus placebo
Timepoint [3] 0 0
24 weeks
Secondary outcome [4] 0 0
Part 2: Proportion of subjects who had at least 50% reduction in mast cell burden
Timepoint [4] 0 0
24 weeks
Secondary outcome [5] 0 0
Parts 1 & 2: Safety and tolerability of bezuclastinib as assessed by number of adverse events
Timepoint [5] 0 0
Up to 24 weeks
Secondary outcome [6] 0 0
Parts 1, 2, & 3: Change and percent change in patient reported outcome (PRO) measures
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Parts 1 & 3: Change and percent change in serum tryptase
Timepoint [7] 0 0
Up to 12 months
Secondary outcome [8] 0 0
Parts 1 & 3: Change and percent change in bone marrow mast cells
Timepoint [8] 0 0
Up to 18 months
Secondary outcome [9] 0 0
Part 1: Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM
Timepoint [9] 0 0
3 months
Secondary outcome [10] 0 0
Part 2: Determine mean change from baseline in predetermined PRO sub-domain and individual item scores
Timepoint [10] 0 0
24 weeks
Secondary outcome [11] 0 0
Parts 2 & 3: Determine change of the lead (most severe) symptom and lead (most severe) subdomain of the MS2D2 in subjects treated with bezuclastinib versus placebo
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
Part 3: Change and percent change in the levels of KIT D816V mutation allele burden
Timepoint [12] 0 0
Up to 12 months
Secondary outcome [13] 0 0
Part 3: To determine the efficacy of bezuclastinib at the selected dose
Timepoint [13] 0 0
Up to 2 years
Secondary outcome [14] 0 0
Part 3: Usage of concomitant medications as rescue therapy for NonAdvSM and changes from baseline in rescue therapy and best supportive care medications regimen
Timepoint [14] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Key

1. Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):

* Indolent systemic mastocytosis (ISM),
* Bone marrow mastocytosis (BMM)
* Smoldering systemic mastocytosis (SSM)
2. Moderate-to-severe symptoms based on a minimum total symptom scoew (TSS) of the Mastocytosis Activity Score (MAS) and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
4. For patients receiving corticosteroids, the dose must be =10 mg/day of prednisone or equivalent

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Persistent toxicity from previous therapy for NonAdvSM that has not resolved to = Grade 1
2. Diagnosed with any of the following WHO SM classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma
3. Diagnosed with mastocytosis of the skin without systemic involvement
4. Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
5. Received prior cytoreductive therapy or investigational agent for <14 days or 5 half- lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy <28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments
6. Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
7. Received any hematopoietic growth factor support <14 days or 5 half lives of the drug before starting screening assessments
8. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
9. Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug

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
27/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2030
Actual
Sample size
Target
207
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
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United States of America
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Michigan
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United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
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Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Hampshire
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United States of America
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New Jersey
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United States of America
State/province [14] 0 0
New York
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United States of America
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North Carolina
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United States of America
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Ohio
Country [17] 0 0
United States of America
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South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Tennessee
Country [19] 0 0
United States of America
State/province [19] 0 0
Texas
Country [20] 0 0
United States of America
State/province [20] 0 0
Utah
Country [21] 0 0
Austria
State/province [21] 0 0
Linz
Country [22] 0 0
Austria
State/province [22] 0 0
Wien
Country [23] 0 0
Belgium
State/province [23] 0 0
Edegem
Country [24] 0 0
Belgium
State/province [24] 0 0
La Louvière
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Canada
State/province [27] 0 0
Quebec
Country [28] 0 0
Czechia
State/province [28] 0 0
Praha 10
Country [29] 0 0
France
State/province [29] 0 0
Marseille
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France
State/province [30] 0 0
Paris
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France
State/province [31] 0 0
Toulouse
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Germany
State/province [32] 0 0
Aachen
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Hamburg
Country [35] 0 0
Germany
State/province [35] 0 0
Kiel
Country [36] 0 0
Germany
State/province [36] 0 0
Mannheim
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Greece
State/province [37] 0 0
Athens
Country [38] 0 0
Ireland
State/province [38] 0 0
Cork
Country [39] 0 0
Ireland
State/province [39] 0 0
Dublin
Country [40] 0 0
Italy
State/province [40] 0 0
Bologna
Country [41] 0 0
Italy
State/province [41] 0 0
Catania
Country [42] 0 0
Italy
State/province [42] 0 0
Firenze
Country [43] 0 0
Italy
State/province [43] 0 0
Pavia
Country [44] 0 0
Italy
State/province [44] 0 0
Ravenna
Country [45] 0 0
Italy
State/province [45] 0 0
Rome
Country [46] 0 0
Italy
State/province [46] 0 0
Verona
Country [47] 0 0
Netherlands
State/province [47] 0 0
Groningen
Country [48] 0 0
Netherlands
State/province [48] 0 0
Rotterdam
Country [49] 0 0
Norway
State/province [49] 0 0
Oslo
Country [50] 0 0
Poland
State/province [50] 0 0
Gdansk
Country [51] 0 0
Poland
State/province [51] 0 0
Lublin
Country [52] 0 0
Spain
State/province [52] 0 0
Barcelona
Country [53] 0 0
Spain
State/province [53] 0 0
Madrid
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Spain
State/province [54] 0 0
Toledo
Country [55] 0 0
Switzerland
State/province [55] 0 0
Basel
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cogent Biosciences, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib.
Trial website
https://clinicaltrials.gov/study/NCT05186753
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Rachael Easton, MD, PhD
Address 0 0
Cogent Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Hina Jolin, PharmD
Address 0 0
Country 0 0
Phone 0 0
+1 (833) 411-6976
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/NCT05186753