MF-300 for Treatment of Age-Related Sarcopenia

Inclusion Criteria:

• Subjects must meet all of the following criteria to be eligible for participation in the study:
• 1. Capable of giving signed informed consent that includes agreement to comply with the requirements described in the informed consent form (ICF) and in this protocol.
• 2. Male or non-pregnant, non-lactating female aged ≥65 years old at the time of signing the informed consent.
• 3. Presence of sarcopenia as defined by the Sarcopenia Definitions and Outcomes Consortium (SDOC) at Screening and Baseline
• a. Low grip strength: <35.5 kg for male; <20 kg for female using JAMAR hydraulic handheld isometric dynamometer AND
• b. Slowness: usual gait speed over 4 meters of <0.8 m/s
• 4. Total Short Physical Performance Battery (SPPB) score within the range of 4 - 8 points (inclusive) at Screening and Baseline with a time to complete the 5xCSTof ≥14.0 to ≤40.0 seconds.
• 5. Female subjects must have no childbearing potential.
• 6. Male subjects must be non-fertile, vasectomized (vasectomy performed 4 months or more prior to the first dosing), or truly abstinent of heterosexual intercourse and agree to remain abstinent for duration of study and for 30 days from last administration of Study Drug, or heterosexual partner is not of child bearing potential, or subject is willing to continue using 2 medically acceptable forms of birth control from Day -1 until at least 30 days after the last administration of Study Drug.
• 7. Body mass index (BMI) ≤35.0 kg/m2.

Exclusion Criteria:

• Subjects who meet any of the following criteria will be excluded from participating in the study:
• 1. History of a pelvic or lower limb fracture (e.g., femur, tibia) within the past 6 months with persistent negative impact on lower extremity function or any significant impairment or disease adversely impacting gait. Individuals with hip and/or knee replacement performed >12 months prior to Screening are eligible for enrollment if their activity status has stabilized.
• 2. Presence of distal upper extremity impairment either due to prior recent injury or disease (e.g., tenosynovitis, rheumatoid arthritis).
• 3. Presence of acute immobility post-acute hospital admission.
• 4. Confirmed diagnosis of significant psychiatric disease (e.g., dementia/Alzheimer's disease, schizophrenia, severe depression or bipolar disorder). Individuals with adequately treated depression are eligible for enrollment.
• 5. Neurological injury/disorder with significant persistent functional deficit (e.g., stroke with hemiparesis, spinal cord injury, muscular dystrophy, multiple sclerosis, polymyositis, dermatomyositis, myopathy/myositides, myasthenia gravis, Parkinson's disease, peripheral polyneuropathy).
• 6. Intraocular surgery and laser procedures for refractive correction within 6 months prior to Screening.
• 7. Known history of glaucoma or evidence suggestive of glaucoma at Screening, including elevated intraocular pressure as measured by tonometry, as determined by the Investigator.
• 8. Vitamin D deficiency defined as 25-OH-vitamin D levels <8.0 ng/mL (20 nmol/L).
• 9. Hemoglobin concentration below 11.0 g/dL (110 g/L) for males or below 10.0 g/dL (100 g/L) for females at Screening.
• 10. Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 calculated by central lab using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation.
• 11. History of confirmed chronic obstructive pulmonary disease with a severity Grade >2 on the Medical Research Council Dyspnea Scale.
• 12. Confirmed rheumatoid arthritis or other systemic autoimmune disease requiring immunosuppressive therapy or corticosteroids >10 mg/day prednisone equivalent, acquired immunodeficiency syndrome (AIDS), medically confirmed diagnosis of chronic fatigue syndrome, long COVID, or type 1 diabetes mellitus.
• 13. History of or ongoing gastrointestinal (GI) conditions (e.g., active and chronic colitis, small or large bowel resection, gastric bypass or equivalent) that would interfere with drug tolerance or absorption.
• 14. Abnormal liver function tests such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), or serum bilirubin (except Gilbert's Disease) determined based on the following criteria:
• a. Any single transaminase may not exceed 3x the upper limit of normal (ULN). A single parameter elevated up to and including 3x ULN should be re-checked as soon as possible, and always prior to enrollment/randomization, to rule out any lab error.
• b. If the total bilirubin level is above the ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. In any case, total bilirubin should not exceed the value of 1.6 mg/dL.
• 15. Platelet count <75,000/mm3.
• 16. Known history or presence of severe active acute or chronic liver disease (e.g., cirrhosis) or conditions with hepatotoxic potential (e.g., known gallbladder or bile duct disease, acute or chronic pancreatitis).
• 17. Confirmed diagnosis of heart failure classified as New York Heart Association Class III and IV (e.g., dilated cardiomyopathy).
• 18. Myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention (e.g., angioplasty or stent placement), or deep vein thrombosis/pulmonary embolism within 12 weeks of Screening. Subjects with current/active unstable angina are excluded.
• 19. Severe cardiac valve disorders or defects (e.g., aortic or mitral stenosis).
• 20. Severe pulmonary hypertension uncontrolled with medication.
• 21. Clinically significant cardiac arrhythmia requiring medical intervention in the past 3 months prior to Screening (e.g., supraventricular tachycardia, atrial fibrillation with rapid ventricular rate, automated implantable cardioverter defibrillator with discharge).
• 22. Chest pain, severe shortness of breath, or occurrence of other safety concerns during the screening or assessments.
• 23. Active cancer (i.e., under current treatment), or cancer requiring treatment in the last 5 years except for nonmelanoma skin cancers or cancers with excellent prognosis (e.g., early-stage prostate or breast cancer, carcinoma in situ of the uterine cervix).
• 24. Active systemic infection requiring hospitalization or treatment with intravenous anti-infectives or antibiotics within 4 weeks of Screening or randomization.
• 25. Any chronic active infection (e.g., human immunodeficiency virus [HIV], hepatitis B or C, tuberculosis, etc.), to be confirmed prior to randomization. Subjects receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study.
• 26. Active alcohol/drug abuse, or alcohol/drug treatment <12 months prior to Screening; subjects having successfully completed an alcohol/drug treatment program >12 months prior to Screening with sustained abstinence are eligible.
• 27. Individuals who require routine and regular (e.g., daily) assistance from another person to complete one or more basic activities of daily living (ADL) (e.g., bathing, dressing, toileting, feeding, grooming) regardless of where they reside. Assistance with instrumental ADL (e.g., shopping, meal preparation, housework) is permitted.
• 28. Mini Mental State Examination score <24 at Screening.
• 29. Presence of severe malnutrition determined by Mini Nutritional Assessment®-Short Form (MNA®-SF) score ≤9.
• 30. Poorly controlled blood pressure defined as systolic blood pressure >180 or <80 mmHg or diastolic blood pressure >100 or <40 mmHg at Screening or randomization.
• 31. Uncontrolled type 2 diabetes mellitus (i.e., hemoglobin A1c [HbA1c] >8.5% or frequent hypoglycemia).
• 32. Uncontrolled or insufficiently managed hypothyroidism or hyperthyroidism. Hypothyroid subjects who are not on a stable dose of thyroid hormone replacement therapy or have changed the dose of thyroid hormone replacement therapy within the 6 weeks prior to Screening are not eligible for the study.
• 33. Participation in another investigational drug, biologic, or device study, with less than 30 days or less than 5 half-lives from the last dose of investigational product to randomization, whichever is longer, or any other type of medical research judged to be scientifically or medically incompatible with this study.
• 34. Use of any therapies known to affect muscle mass, including androgens, androgen supplements [including over-the-counter dehydroepiandrosterone (DHEA)], gonadotropin releasing hormone (GnRH) analogues, anti-androgens, anti-estrogens (e.g., tamoxifen), progestins with known androgenic component (e.g., norethindrone acetate, megestrol acetate, high-dose tibolone [2.5 mg]), recombinant human growth hormone, growth hormone receptor antagonists (e.g., pregvisomant), oral selective beta-2 agonists, dronabinol or any nutritional supplement other than protein marketed as a muscle anabolic within 3 months prior to Screening.
• 35. Use of any anabolic steroids (e.g., testosterone) within 3 months prior to Screening.
• 36. Use of glucagon-like peptide-1 (GLP-1) receptor agonist or GLP-1/GIP dual agonist therapy for any indication (e.g., obesity, type 2 diabetes mellitus, or metabolic dysfunction-associated steatohepatitis [MASH]) within the 6 months prior to Screening.
• 37. Systemic corticosteroid use for at least 3 months (in the last year) prior to Screening at a daily dose greater than 10 mg prednisone equivalent.
• 38. Use of non-antibody immunosuppressive therapy (e.g., cyclosporine, methotrexate, tacrolimus, cyclophosphamide) within 3 months of Screening.
• 39. Chronic use of a beta blocker initiated within the 3 months prior to Screening.
• 40. Chronic use (continuous use >7 days) of acetaminophen or cyclooxygenase (COX)-1 and/or COX-2 inhibitors (e.g., aspirin, other nonsteroidal anti-inflammatory drugs [NSAIDs] such as ibuprofen, naproxen, diclofenac, or celecoxib) within the 3 weeks of Day 1 and unable to refrain from chronic use over the course of the study.