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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05186753
Recruitment Status : Recruiting
First Posted : January 11, 2022
Last Update Posted : May 3, 2023
Sponsor:
Information provided by (Responsible Party):
Cogent Biosciences, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
SSM Mastocytosis, Indolent Mastocytosis, Systemic Mastocytosis Drug: Bezuclastinib Tablets (Formulation A) Drug: Bezuclastinib Tablets (Formulation B) Drug: Placebo Tablets Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : June 27, 2022
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: (Part 1a) Bezuclastinib Dose 1 + BSC Drug: Bezuclastinib Tablets (Formulation A)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486
Experimental: (Part 1a) Bezuclastinib Dose 2 + BSC Drug: Bezuclastinib Tablets (Formulation A)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486
Placebo Comparator: (Part 1a) Placebo + BSC Drug: Placebo Tablets
Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 1b) Bezuclastinib Dose 1 + BSC Drug: Bezuclastinib Tablets (Formulation B)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486
Experimental: (Part 1b) Bezuclastinib Dose 2 + BSC Drug: Bezuclastinib Tablets (Formulation B)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486
Placebo Comparator: (Part 1b) Placebo + BSC Drug: Placebo Tablets
Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 2) Bezuclastinib Selected Dose + BSC Drug: Bezuclastinib Tablets (Formulation B)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486
Placebo Comparator: (Part 2) Placebo + BSC Drug: Placebo Tablets
Placebo will be administered orally, once daily continuously for 28-day cycles
Experimental: (Part 3) Bezuclastinib + BSC Drug: Bezuclastinib Tablets (Formulation A)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486

Drug: Bezuclastinib Tablets (Formulation B)
Bezuclastinib will be administered orally, once daily continuously for 28-day cycles
Other Names:
  • CGT9486
  • PLX9486


Outcome Measures
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Primary Outcome Measures :
  1. Part 1: Determine recommended dose of bezuclastinib (CGT9486) in subjects with NonAdvSM [ Time Frame: 3 months ]
    Selection of the recommended dose to be used in subsequent parts of the study.

  2. Part 2: Efficacy of bezuclastinib at the selected dose versus placebo [ Time Frame: 6 months ]
    Mean absolute change in a disease-specific patient reported outcome (PRO)

  3. Part 3: Safety and tolerability of bezuclastinib as assessed by number of adverse events [ Time Frame: Up to 24 months ]
    CTCAE v5


Secondary Outcome Measures :
  1. Safety and tolerability of bezuclastinib as assessed by number of adverse events [ Time Frame: Up to 24 months ]
    CTCAE v5

  2. Proportion of subjects who had at least 50% reduction in serum tryptase [ Time Frame: Up to 24 months ]
  3. Proportion of subjects who had at least 50% reduction in mast cell burden [ Time Frame: Up to 24 months ]
  4. Proportion of subjects who had at least a 50% reduction in peripheral blood D816V allele fraction [ Time Frame: Up to 24 months ]
  5. Change and percent change in patient reported outcome (PRO) measures [ Time Frame: Up to 24 months ]
  6. Change and percent change in serum tryptase [ Time Frame: Up to 24 months ]
  7. Change and percent change in bone marrow mast cells [ Time Frame: Up to 24 months ]
  8. Change and percent change in the levels of KIT D816V mutation allele burden [ Time Frame: Up to 24 months ]
  9. Assess the pharmacokinetics (PK) of bezuclastinib in subjects with NonAdvSM [ Time Frame: Up to 24 months ]
    Plasma concentrations of CGT9846

  10. Change and percent change in the Mast Cell Quality of Life (MC-QOL) Score [ Time Frame: up to 24 months ]
    Scale of 0-100, higher numbers represent more severe impairment to quality of life.

  11. Change and percent change in 12-item Short Form Health Survey (SF-12) [ Time Frame: up to 24 months ]
    Scale of 0-100, higher numbers represent better symptom outcomes

  12. Change and percent change in EuroQol 5 Dimensions 5 Levels (EQ 5D-5L) [ Time Frame: up to 24 months ]
    Scale of 0-100, higher numbers represent better symptom outcomes

  13. Determine responder rates of subjects treated with bezuclastinib at the selected dose [ Time Frame: 6 months ]
    Response rate based on reduction in disease specific PRO


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05186753


Contacts
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Contact: Hina Jolin, PharmD +1 (617) 945-5576 hina.jolin@cogentbio.com

Locations
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Sponsors and Collaborators
Cogent Biosciences, Inc.
Investigators
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Study Director: Rachael Easton, MD, PhD Cogent Biosciences
More Information
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Responsible Party: Cogent Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT05186753    
Other Study ID Numbers: CGT9486-21-202
First Posted: January 11, 2022    Key Record Dates
Last Update Posted: May 3, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cogent Biosciences, Inc.:
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
Additional relevant MeSH terms:
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Mastocytosis
Mastocytosis, Systemic
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
 Neoplasms by Histologic Type
Neoplasms
Mast Cell Activation Disorders
Immune System Diseases