Clinical Trial TitleA multi-part, randomized, double-blind, placebo-controlled phase 2 clinical study of the safety and efficacy of CTG9486 in subjects with nonadvanced systemic mastocytosis
National Clinical Trial Number:NCT05186753
Clinical Trial Protocol Description:
The purpose of this study is to find out if CGT9486, also known as bezuclastinib, is safe and effective for treating for treating non-advanced systemic mastocytosis.
Clinical Trial Eligibility Criteria:
In order to participate you must meet the following criteria:
- Have been diagnosed with 1 of the following diagnoses according to the 2016 World Health Organization (WHO) classification for systemic mastocytosis (SM): indolent systemic mastocytosis (IM) or Smoldering systemic mastocytosis (SSM).
- Have inadequate control of SM symptoms defined as Mastocytosis Activity Score (MAS) total score of greater than or equal to 26 after a stable regimen of 2 or more antimediator therapies is established (no modifications for 14 days). Acceptable antimediator therapies for baseline supportive care (BSC):
- Histamine receptor type 1 (H1) antagonist
- Histamine receptor type 2 (H2) antagonist
- Cromolyn sodium
- Leukotriene receptor antagonist
- Corticosteroids (less than or equal to 10 mg/day prednisone or equivalent)
- Proton pump inhibitor
- Able to provide written informed consent.
- Able and willing to commit to study assessments and visit schedule.
- Are 18 years of age or older.
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2: Fully active, able to carry on all pre-disease performance without restriction; Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature: light house work, office work; Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours.
- Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits specified in the protocol.
- For women of childbearing potential (defined as physiologically and anatomically capable of becoming pregnant), confirmation of a negative serum pregnancy test and agreement to the use of a highly effective method of contraception or at least 2 effective methods at the same time during the study treatment period and for up to 6 months after the last dose of study drug; for male subjects, agreement to use effective barrier contraception (condoms) during the study treatment period and for up to 6 months after the last dose of study drug.
- Able to swallow pills.
You will be excluded from the study if any of the following criteria apply to you:
- Have persistent toxicity from previous therapy for non-advanced systemic mastocytosis (NonAdvSM) that has not resolved to less than or equal to Grade 1.
- Have been diagnosed with any of the following WHO systemic mastocytosis (SM) classifications: bone marrow mastocytosis, advanced systemic mastocytosis including SM with associated hematologic neoplasm, aggressive SM, mast cell leukemia; or mast cell sarcoma.
- Have been diagnosed with mastocytosis of the skin without systemic involvement.
- Have received prior treatment with any targeted KIT inhibitor.
- Have received prior cytoreductive therapy or investigational agent for less than 14 days or 5 half-lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy for less than 28 days or 5 half-lives of the drug (whichever is longer), before starting screening assessments.
- Have received radiotherapy or psoralen and ultraviolet A therapy less than 14 days before starting screening assessments.
- Have received any hematopoietic growth factor support less than 14 days before starting screening assessments.
- Have clinically significant cardiac disease, defined by any of the following:
- Clinically significant cardiac arrhythmias, and/or the need for anti-arrhythmic therapy (excluding beta blockers or digoxin). (Subjects with controlled atrial fibrillation are not excluded.)
- Congenital long QT syndrome or concomitant medications known to prolong the QT interval except those required for infections that carry a low risk of QTc prolongation.
- A marked baseline prolongation of QT/QTc interval (repeated demonstration of a QTc interval greater than 480 ms).
- History of clinically significant cardiac disease or congestive heart failure > New York Heart Association Class II. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months prior to enrollment.
- Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before study drug initiation (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the first dose of study drug).
- Have any other concurrent severe known disease or concurrent severe and/or uncontrolled medical condition (uncontrolled diabetes or active uncontrolled infection), either of which could compromise participation in the study.
- Are seropositive for HIV 1 or 2 antibody, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody. Subjects with a positive HCV antibody may be eligible if HCV RNA is undetectable on a quantitative HCV RNA assay, following discussion with the Medical Monitor.
- Have active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening. NOTE: Oral antibiotics for a controlled infection are permitted. Subjects on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met.
- Have a history of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study.
- Have been diagnosed with or treated for malignancy within the prior 3 years before enrollment or expected to need treatment for an active malignancy. (The following are allowed within 3 years of study enrollment if the subject has received definitive local therapy [surgical excision, external beam radiation, or other local therapy with curative intent]: non-melanoma skin cancers, localized prostate cancer, or carcinoma in situ.)
- Are pregnant or currently breastfeeding.
- Have received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives before the first dose of study drug, whichever is longer, or the need to continue treatment with strong CYP3A4 inhibitors or inducers during the study.
- Have a need for treatment with steroids (more than 10 mg/day prednisone or equivalent). Subjects on a stable dose of less than or equal to10 mg/day prednisone or equivalent are eligible.
- Have known hypersensitivity to CGT9486 or any of its components.
- Have a history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
- Are illiterate, unable, or unwilling to complete daily PRO assessments in the study.
- Have any condition that could hamper compliance with the study protocol in the judgment of the Investigator.
This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.