Effect of Linvemastat in Patients With Partially Controlled Asthma (syMMPonia)

Exclusion Criteria

• •Pregnant or breastfeeding.
• •Current smoker (including vaping) or cessation of smoking within the 6 months prior to Day 1, or \> 10 pack-year history of smoking.
• •Participation in another clinical trial of an investigational agent within 3 months (small molecule) / 6 months (biologics) or 5 half-lives (if known) of the agent, whichever is longer, prior to randomization.
• •Evidence of COVID-19 infection at Screening, as judged by the Investigator.
• •Advanced congestive heart failure \[New York Heart Association (NYHA) class 3 or 4\].
• •Known hypersensitivity to any component of the formulation of linvemastat or any component of the excipient.
• •Live or messenger ribonucleic acid (mRNA) vaccination within 2 weeks before Day 1 or inoculation with a live or mRNA vaccine is planned during study participation.
• •History of solid organ transplant.
• •Anti-immunoglobulin E (IgE) therapy \[e.g., omalizumab (Xolair®)\] within 130 days prior to Screening or any other biologic therapy \[including anti-TSLP, anti-IL-4/4R or IL-5/5R monoclonal antibodies (mAb)\] or systemic immunosuppressant (e.g., methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 2 months or 5 half-lives prior to Screening, whichever is longer.
• •Evidence of active tuberculosis (TB) infection at Screening, as judged by the Investigator.
• •Active acute or chronic psychiatric illness that, in the opinion of the Investigator, may prevent from complying with study instructions.
• •Known positive history of malignancy within 5 years of Screening (with the exception of basal cell skin cancer, carcinoma in-situ of the cervix, or low-risk prostate cancer after curative therapy).
• •Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) infection at Screening.
• •Concurrent emphysema.
• •Use of any therapeutics that are strong inhibitors and inducers of CYP3A4 or CYP2C8 \[e.g., rifampicin, ketoconazole, phenytoin, ritonavir, macrolide antibiotics (e.g., telithromycin), and carbamazepine\].
• •History of liver dysfunction, including patients with moderate (Child-Pugh B) or severe (Child-Pugh C) impairment or disordered coagulation.
• •Abnormal ECG: ventricular arrhythmias (non-sustained ventricular tachycardia \[VT\], multifocal or frequent premature ventricular contractions, clinically significant bundle branch block or axis deviation \[as assessed by PI\], or abnormal Q waves). In the case of a corrected QT interval using Fridericia's formula (QTcF) interval \>450 ms (men) or \>480 ms (women; patients with bundle branch block) or PR (P to QRS) interval outside the range of 120 to 220 ms, the assessment may be repeated once for eligibility determination at Screening or Baseline.
• •Known uncontrolled hypertension or diabetes at the discretion of the Investigator.
• •Any condition that required hospitalization (except for asthma exacerbation) within the 3 months prior to Day 1 or is likely to require so during the study.
• •Clinically significant abnormalities in the Screening physical examination, medical history, vital signs, ECG, or clinical laboratory tests that are not known to be due to concurrent asthma in the opinion of the Investigator and Medical Monitor should preclude the patient's participation in the clinical study.
• •The following laboratory parameters are excluded:
• •1. Hemoglobin (Hg) \<10 g/dL (100 g/L)
• •2. White blood cells (WBC) \< 3000/μL (\< 3000/mm3). African American patients who are known to have low WBC of \< 3000/μL but ≥ 1500/μL will be eligible.
• •3. Platelet count \< 70,000/μL (70,000/mm3)
• •4. Serum creatinine \> 1.5 x upper limit of normal (ULN)
• •5. Glomerular filtration rate ≤ 60 mL/min/1.73 m2 or evidence of acute kidney injury or history of severe hypersensitivity reactions to gadolinium-based contrast agents
• •6. Serum total bilirubin \> 1.5 ULN
• •7. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x ULN or serum alkaline phosphatase \> 2 x ULN