(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis

Mastocytosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05186753
• Other study ID #: CGT9486-21-202
• Status: Recruiting
• Phase: Phase 2
• Start date: June 27, 2022
• Est. completion date: November 2026

Study information

• Verified date: April 2024
• Source: Cogent Biosciences, Inc.
• Contact: Hina Jolin, PharmD
• Phone: +1 (617) 945-5576
• Email: hina.jolin[@]cogentbio.com
• Is FDA regulated: No
• 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

Related Conditions & MeSH terms

• Mastocytosis
• SSM

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
Belgium	Antwerp University Hospital (UZA)	Edegem
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Toronto Allergy and Asthma Clinic	Toronto	Ontario
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
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
Greece	Attikon University General Hospital Athens	Athens
Ireland	St. James's Hospital	Dublin
Italy	IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Policlinico Universitario Agostino Gemelli	Rome
Netherlands	University Medical Center Groningen	Groningen
Norway	Oslo University Hospital	Oslo
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii	Gdansk
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Instituto de Estudios de Mastocitosis de Castilla La Mancha-Hospital Virgen del Valle	Toledo
Switzerland	University Hospital Basel	Basel
United Kingdom	Guy's Hospital	London
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	University of Cincinnati	Cincinnati	Ohio
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	Icahn School of Medicine at Mount Sinai	New York	New York
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,  Belgium,  Canada,  Czechia,  France,  Germany,  Greece,  Ireland,  Italy,  Netherlands,  Norway,  Poland,  Spain,  Switzerland,  United Kingdom, 

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