Back to results(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
Primary Purpose
SSM, Mastocytosis, Indolent, Mastocytosis, Systemic
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bezuclastinib Tablets (Formulation A)
Bezuclastinib Tablets (Formulation B)
Placebo Tablets
Sponsored by
About this trial
This is an interventional treatment trial for SSM focused on measuring Systemic Mastocytosis, Immune Complex Diseases, Immune System Diseases, Hypersensitivity, Hematologic Diseases, NonAdvSM, D816V, KIT D816V, Bezuclastinib, CGT9486, CGT, PLX, Nonadvanced Systemic Mastocytosis, PLX9486, Indolent Systemic Mastocytosis, ISM, Smoldering Systemic Mastocytosis
Eligibility Criteria
Key Inclusion Criteria:
Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
- Indolent systemic mastocytosis (ISM)
- Smoldering systemic mastocytosis (SSM)
- Moderate-to-severe symptoms based on a disease-specific PRO and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent
Key Exclusion Criteria:
- 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
- Diagnosed with mastocytosis of the skin without systemic involvement
- Received prior treatment with any targeted KIT inhibitor
- 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
- Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
- Received any hematopoietic growth factor support <14 days before starting screening assessments
- History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
- Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
Sites / Locations
- Mayo Clinic ArizonaRecruiting
- One of a Kind Clinical Research CenterRecruiting
- Modena Allergy and Asthma ClinicalRecruiting
- Innovative Research of West FloridaRecruiting
- Maya Research CenterRecruiting
- Mayo Clinic - JacksonvilleRecruiting
- Mid Florida Hematology and Oncology CenterRecruiting
- Emory UniversityRecruiting
- Rush UniversityRecruiting
- Walter Reed National Military Medical CenterRecruiting
- Allervie Clinical ResearchRecruiting
- Chesapeake Research CenterRecruiting
- Brigham and Women's HospitalRecruiting
- Dana Farber Cancer InstituteRecruiting
- University of MichiganRecruiting
- Mayo Clinic- RochesterRecruiting
- Washington University at St. LouisRecruiting
- Dartmouth Hitchcock Medical CenterRecruiting
- Duke UniversityRecruiting
- The Ohio State UniversityRecruiting
- Vanderbilt University Medical CenterRecruiting
- AIR CareRecruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- Royal Prince Alfred HospitalRecruiting
- Royal Adelaide HospitalRecruiting
- Toronto Allergy and Asthma ClinicRecruiting
- AP-HP- Hopital Pitie-SalpetriereRecruiting
- CHU de Toulouse - Hopital LarreyRecruiting
- Universitaetsklinikum Aachen, AoeRRecruiting
- Charité Universitätsmedizin BerlinRecruiting
- University Medical Centre MannheimRecruiting
- Fondazione IRCCS Policlinico San MatteoRecruiting
- Policlinico Universitario Agostino GemelliRecruiting
- University Medical Center GroningenRecruiting
- Hospital Universitario Vall d'HebronRecruiting
- Hospital Universitario Ramon y CajalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Arm Label
(Part 1a) Bezuclastinib Dose 1 + BSC
(Part 1a) Bezuclastinib Dose 2 + BSC
(Part 1a) Placebo + BSC
(Part 1b) Bezuclastinib Dose 1 + BSC
(Part 1b) Bezuclastinib Dose 2 + BSC
(Part 1b) Placebo + BSC
(Part 2) Bezuclastinib Selected Dose + BSC
(Part 2) Placebo + BSC
(Part 3) Bezuclastinib + BSC
Arm Description
Outcomes
Primary Outcome Measures
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
Selection of the recommended dose to be used in subsequent parts of the study.
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
Mean absolute change in a disease-specific patient reported outcome (PRO)
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
CTCAE v5
Secondary Outcome Measures
Safety and tolerability of bezuclastinib as assessed by number of adverse events
CTCAE v5
Proportion of subjects who had at least 50% reduction in serum tryptase
Proportion of subjects who had at least 50% reduction in mast cell burden
Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction
Change and percent change in patient reported outcome (PRO) measures
Change and percent change in serum tryptase
Change and percent change in bone marrow mast cells
Change and percent change in the levels of KIT D816V mutation allele burden
Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM
Plasma concentrations of CGT9846
Change and percent change in the Mast Cell Quality of Life (MC-QOL) Score
Scale of 0-100, higher numbers represent more severe impairment to quality of life.
Change and percent change in 12-item Short Form Health Survey (SF-12)
Scale of 0-100, higher numbers represent better symptom outcomes
Change and percent change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L)
Scale of 0-100, higher numbers represent better symptom outcomes
Determine responder rates of subjects treated with bezuclastinib at the selected dose
Response rate based on reduction in disease specific PRO
Full Information
NCT ID
NCT05186753
First Posted
November 19, 2021
Last Updated
August 2, 2023
Sponsor
Cogent Biosciences, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05186753
Brief Title
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cogent Biosciences, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SSM, Mastocytosis, Indolent, Mastocytosis, Systemic, Mastocytosis
Keywords
Systemic Mastocytosis, Immune Complex Diseases, Immune System Diseases, Hypersensitivity, Hematologic Diseases, NonAdvSM, D816V, KIT D816V, Bezuclastinib, CGT9486, CGT, PLX, Nonadvanced Systemic Mastocytosis, PLX9486, Indolent Systemic Mastocytosis, ISM, Smoldering Systemic Mastocytosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
In Part 1a and 1b of the study, patients with NonAdvSM will be randomly assigned to 1 of 2 dose levels of bezuclastinib plus BSC, or to placebo plus BSC. Upon analysis of the Part 1 data, a dose will be selected for Part 2. In Part 2, patients with NonAdvSM will be randomly assigned to the selected dose of bezuclastinib plus BSC, or to placebo plus BSC.
Patients who complete Part 1 or Part 2 may participate in Part 3 in which all patients will receive bezuclastinib plus BSC.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
138 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
(Part 1a) Bezuclastinib Dose 1 + BSC
Arm Type
Experimental
Arm Title
(Part 1a) Bezuclastinib Dose 2 + BSC
Arm Type
Experimental
Arm Title
(Part 1a) Placebo + BSC
Arm Type
Placebo Comparator
Arm Title
(Part 1b) Bezuclastinib Dose 1 + BSC
Arm Type
Experimental
Arm Title
(Part 1b) Bezuclastinib Dose 2 + BSC
Arm Type
Experimental
Arm Title
(Part 1b) Placebo + BSC
Arm Type
Placebo Comparator
Arm Title
(Part 2) Bezuclastinib Selected Dose + BSC
Arm Type
Experimental
Arm Title
(Part 2) Placebo + BSC
Arm Type
Placebo Comparator
Arm Title
(Part 3) Bezuclastinib + BSC
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bezuclastinib Tablets (Formulation A)
Other Intervention Name(s)
CGT9486, PLX9486
Intervention Description
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Bezuclastinib Tablets (Formulation B)
Other Intervention Name(s)
CGT9486, PLX9486
Intervention Description
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Intervention Type
Drug
Intervention Name(s)
Placebo Tablets
Intervention Description
Placebo will be administered orally, once daily continuously for 28-day cycles
Primary Outcome Measure Information:
Title
Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM
Description
Selection of the recommended dose to be used in subsequent parts of the study.
Time Frame
3 months
Title
Part 2: Efficacy of bezuclastinib at the selected dose versus placebo
Description
Mean absolute change in a disease-specific patient reported outcome (PRO)
Time Frame
6 months
Title
Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events
Description
CTCAE v5
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Safety and tolerability of bezuclastinib as assessed by number of adverse events
Description
CTCAE v5
Time Frame
Up to 24 months
Title
Proportion of subjects who had at least 50% reduction in serum tryptase
Time Frame
Up to 24 months
Title
Proportion of subjects who had at least 50% reduction in mast cell burden
Time Frame
Up to 24 months
Title
Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction
Time Frame
Up to 24 months
Title
Change and percent change in patient reported outcome (PRO) measures
Time Frame
Up to 24 months
Title
Change and percent change in serum tryptase
Time Frame
Up to 24 months
Title
Change and percent change in bone marrow mast cells
Time Frame
Up to 24 months
Title
Change and percent change in the levels of KIT D816V mutation allele burden
Time Frame
Up to 24 months
Title
Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM
Description
Plasma concentrations of CGT9846
Time Frame
Up to 24 months
Title
Change and percent change in the Mast Cell Quality of Life (MC-QOL) Score
Description
Scale of 0-100, higher numbers represent more severe impairment to quality of life.
Time Frame
up to 24 months
Title
Change and percent change in 12-item Short Form Health Survey (SF-12)
Description
Scale of 0-100, higher numbers represent better symptom outcomes
Time Frame
up to 24 months
Title
Change and percent change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L)
Description
Scale of 0-100, higher numbers represent better symptom outcomes
Time Frame
up to 24 months
Title
Determine responder rates of subjects treated with bezuclastinib at the selected dose
Description
Response rate based on reduction in disease specific PRO
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM):
Indolent systemic mastocytosis (ISM), including the bone marrow mastocytosis subvariant
Smoldering systemic mastocytosis (SSM)
Moderate-to-severe symptoms based on a disease-specific PRO and after establishing a stable regimen of at least 2 antimediator therapies over a 14-day eligibility period
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
For patients receiving corticosteroids, the dose must be ≤10 mg/day of prednisone or equivalent
Key Exclusion Criteria:
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
Diagnosed with mastocytosis of the skin without systemic involvement
Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM
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
Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments
Received any hematopoietic growth factor support <14 days before starting screening assessments
History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hina Jolin, PharmD
Phone
+1 (617) 945-5576
Email
hina.jolin@cogentbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachael Easton, MD, PhD
Organizational Affiliation
Cogent Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Individual Site Status
Recruiting
Facility Name
One of a Kind Clinical Research Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Recruiting
Facility Name
Modena Allergy and Asthma Clinical
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Name
Innovative Research of West Florida
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Individual Site Status
Recruiting
Facility Name
Maya Research Center
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Recruiting
Facility Name
Mid Florida Hematology and Oncology Center
City
Orange City
State/Province
Florida
ZIP/Postal Code
32763
Country
United States
Individual Site Status
Recruiting
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
Individual Site Status
Recruiting
Facility Name
Allervie Clinical Research
City
Glenn Dale
State/Province
Maryland
ZIP/Postal Code
20769
Country
United States
Individual Site Status
Recruiting
Facility Name
Chesapeake Research Center
City
White Marsh
State/Province
Maryland
ZIP/Postal Code
21162
Country
United States
Individual Site Status
Recruiting
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Mayo Clinic- Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University at St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03766
Country
United States
Individual Site Status
Recruiting
Facility Name
Duke University
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Individual Site Status
Recruiting
Facility Name
AIR Care
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Toronto Allergy and Asthma Clinic
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1E2
Country
Canada
Individual Site Status
Recruiting
Facility Name
AP-HP- Hopital Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Name
CHU de Toulouse - Hopital Larrey
City
Toulouse
ZIP/Postal Code
31400
Country
France
Individual Site Status
Recruiting
Facility Name
Universitaetsklinikum Aachen, AoeR
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Individual Site Status
Recruiting
Facility Name
Charité Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Individual Site Status
Recruiting
Facility Name
University Medical Centre Mannheim
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Policlinico Universitario Agostino Gemelli
City
Rome
ZIP/Postal Code
168
Country
Italy
Individual Site Status
Recruiting
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis
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