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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05186753
Other study ID # CGT9486-21-202
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date June 27, 2022
Est. completion date November 2026

Study information

Verified date October 2023
Source Cogent Biosciences, Inc.
Contact Hina Jolin, PharmD
Phone +1 (617) 945-5576
Email hina.jolin@cogentbio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 138
Est. completion date November 2026
Est. primary completion date November 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Key Inclusion Criteria: 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), including the bone marrow mastocytosis subvariant - Smoldering systemic mastocytosis (SSM) 2. 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 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 Exclusion Criteria: 1. 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 2. Diagnosed with mastocytosis of the skin without systemic involvement 3. Received prior treatment with any targeted KIT inhibitor with the exception of approved agents for the treatment of SM 4. 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 5. Received radiotherapy or psoralen and ultraviolet A therapy <14 days before starting screening assessments 6. Received any hematopoietic growth factor support <14 days before starting screening assessments 7. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study 8. Need for treatment of corticosteroids at >10 mg/day of prednisone or equivalent

Study Design


Related Conditions & MeSH terms


Intervention

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

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Royal Prince Alfred Hospital Camperdown New South Wales
Canada Toronto Allergy and Asthma Clinic Toronto Ontario
France AP-HP- Hopital Pitie-Salpetriere Paris
France CHU de Toulouse - Hopital Larrey Toulouse
Germany Universitaetsklinikum Aachen, AoeR Aachen
Germany Charité Universitätsmedizin Berlin Berlin
Germany University Medical Centre Mannheim Mannheim
Italy IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola Bologna
Italy Fondazione IRCCS Policlinico San Matteo Pavia
Italy Policlinico Universitario Agostino Gemelli Rome
Netherlands University Medical Center Groningen Groningen
Norway Oslo University Hospital Oslo
Spain Hospital Universitario Vall d'Hebron Barcelona
Spain Hospital Universitario Ramon y Cajal Madrid
United States University of Michigan Ann Arbor Michigan
United States Emory University Atlanta Georgia
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Brigham and Women's Hospital Boston Massachusetts
United States Dana Farber Cancer Institute Boston Massachusetts
United States Rush University Chicago Illinois
United States Innovative Research of West Florida Clearwater Florida
United States The Ohio State University Columbus Ohio
United States AIR Care Dallas Texas
United States Allervie Clinical Research Glenn Dale Maryland
United States Maya Research Center Hialeah Florida
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States Mayo Clinic - Jacksonville Jacksonville Florida
United States Modena Allergy and Asthma Clinical La Jolla California
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States Vanderbilt University Medical Center Nashville Tennessee
United States Mid Florida Hematology and Oncology Center Orange City Florida
United States Mayo Clinic Arizona Phoenix Arizona
United States Duke University Raleigh North Carolina
United States Mayo Clinic- Rochester Rochester Minnesota
United States Washington University at St. Louis Saint Louis Missouri
United States One of a Kind Clinical Research Center Scottsdale Arizona
United States Chesapeake Research Center White Marsh Maryland

Sponsors (1)

Lead Sponsor Collaborator
Cogent Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Netherlands,  Norway,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 3 months
Primary Part 2: Efficacy of bezuclastinib at the selected dose versus placebo Mean absolute change in a disease-specific patient reported outcome (PRO) 6 months
Primary Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events CTCAE v5 Up to 24 months
Secondary Safety and tolerability of bezuclastinib as assessed by number of adverse events CTCAE v5 Up to 24 months
Secondary Proportion of subjects who had at least 50% reduction in serum tryptase Up to 24 months
Secondary Proportion of subjects who had at least 50% reduction in mast cell burden Up to 24 months
Secondary Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction Up to 24 months
Secondary Change and percent change in patient reported outcome (PRO) measures Up to 24 months
Secondary Change and percent change in serum tryptase Up to 24 months
Secondary Change and percent change in bone marrow mast cells Up to 24 months
Secondary Change and percent change in the levels of KIT D816V mutation allele burden Up to 24 months
Secondary Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM Plasma concentrations of CGT9846 Up to 24 months
Secondary 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. up to 24 months
Secondary Change and percent change in 12-item Short Form Health Survey (SF-12) Scale of 0-100, higher numbers represent better symptom outcomes up to 24 months
Secondary Change and percent change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L) Scale of 0-100, higher numbers represent better symptom outcomes up to 24 months
Secondary Determine responder rates of subjects treated with bezuclastinib at the selected dose Response rate based on reduction in disease specific PRO 6 months
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