Study to Determine Optimal Dose, Evaluate the Efficacy and Safety of PRG-N-01 in Patients With Neurofibromatosis Type II

Exclusion Criteria

• •1\) Subjects who have the following past or current medical history confirmed during screening:
• •(1) Malignant tumor requiring treatment (chemotherapy or radiotherapy) or with disease progression within 2 years prior to screening (2) The following heart-related history
• •Uncontrolled hypertension at screening (DBP ≥100 mmHg or SBP ≥160 mmHg despite treatment)
• •Acute coronary syndrome (ACS) within 24 weeks of baseline, clinically significant arrhythmia, cardiomyopathy, unstable angina, NYHA II-IV heart failure, or severe valvular heart disease
• •1. Interstitial lung disease or pulmonary fibrosis
• •2. Cystitis or urinary obstruction within 12 weeks prior to screening
• •3. Blood coagulation disorder
• •4. Severe or active infectious disease requiring antibiotics, antivirals, etc. within 4 weeks prior to screening
• •5. Gastrointestinal disease that currently makes oral administration difficult or may affect absorption (e.g., celiac disease, Crohn's disease, intestinal resection)
• •6. Other diseases that are sufficient to affect the clinical study results at the investigator's discretion.
• •2\) Subjects who have confirmed or need the following drug treatments:
• •1. Chemotherapy, immunotherapy, or myelosuppressive chemotherapy within 4 weeks prior to screening (but, within 6 weeks prior to screening for nitrosourea agents or mitomycin C)
• •2. Monoclonal antibody therapy within 12 weeks prior to screening (but, allowing if more than 3 half-lives have elapsed); stem cell transplantation (but, allowing if there is no evidence of active graft-versus-host disease and more than 12 weeks have elapsed since transplantation)
• •3. Other investigational drugs or devices within 4 weeks prior to screening
• •4. Corticosteroids such as prednisone and prednisolone within 1 week prior to screening (but, allowing if treated with low doses)
• •5. Substrate of strong inhibitor, inducer, or transporter (OCT2, MATE1, MATE2-K) of CYP enzymes (CYP2C8, CYP3A) (but, allowing only if more than 5 times the half-life from baseline has elapsed) 3) Subjects who performed a major surgery within 4 weeks prior to screening (but, allowing minor surgical procedures such as catheter replacement therapy and local biopsy).
• •4\) Subjects who received radiation therapy for the purpose of treating tumors due to NF2 within 24 weeks prior to screening or who require total body irradiation during the clinical study period.
• •5\) Subjects with prosthetics or orthopedic devices that may interfere with the volumetric analysis of target lesions via MRI.
• •6\) Subjects with a known severe hypersensitivity to PRG-N-01 or a concomitant medication or the ingredients or a history of allergic reactions to compounds of similar chemical or biological composition.
• •7\) Female subjects who are pregnant or breastfeeding 8) Women of childbearing potential or men who are unwilling to use an appropriate method of contraception from the date of written consent to 12 weeks after the last dose of PRG-N-01.
• •9\) Other subjects who are deemed unsuitable for participation in this clinical study at the investigator's discretion