Proof-of-Concept Study Evaluating Total Body Weight, Physical Function & Safety of Enobosarm in Patients Treated With GLP-1 Receptor Agonist, for Weight Loss

Exclusion Criteria31

• Any of the following conditions are cause for exclusion from the study:
• Known hypersensitivity or allergy to enobosarm or a GLP-1 receptor agonist
• Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as measured using the chronic kidney disease-epidemiology collaboration (CKD-EPI) calculation (patients with mild and moderate renal failure are not excluded from participation in this study)
• Treatment with any investigational product within < 5 half-lives for each individual investigational product OR within 30 days prior to randomization
• Major surgery (the surgery poses a significant risk to patients life and requires general anesthesia) within 30 days prior to randomization
• Planned major surgery during the course of the study or any cosmetic surgery potentially impacting body composition, e.g., liposuction, implants, or removal of any current implants
• Testosterone, methyltestosterone, oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®), testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other androgenic compounds, including herbals), myostatin inhibitors, apelin receptor agonists, or antiandrogens (flutamide, bicalutamide, abiraterone, enzalutamide, apalutamide, or darolutamide). Previous therapy with testosterone and testosterone-like agents is acceptable with a 30-day washout (if previous testosterone therapy was long term depot within the past 6 months, the site should contact the Medical Monitor) or any other androgenic agent.
• An abnormal ECG result which, based on the investigator's clinical judgment, would place the subject at increased medical risk. A QTcF >450 ms for males and >450 ms for females is also exclusionary from this protocol.
• Concurrently participating in any other interventional or treatment clinical trial.
• Pre-existing liver disease (hepatitis B, uncontrolled hepatitis A, hepatitis C, autoimmune hepatitis, liver cancer, alcohol-associated cirrhosis, alcohol- associated hepatitis, alcohol-associated fatty liver)
• Baseline ALT or AST >3x upper limit of normal
• Baseline total bilirubin levels >upper limit of normal (except in cases of Gilbert's Syndrome)
• History of acute pancreatitis within one year of screening or history of chronic pancreatitis
• Severe gastrointestinal disease, including gastroparesis
• Major depressive disorder diagnosed within 2 years prior to screening (NOTE: a diagnosis of major depressive disorder ≥2 years prior to screening that is stably managed \[with or without pharmacological intervention\] without additional exclusionary history are not excluded from the study), history of other severe psychiatric disorder, including schizophrenia and bipolar disorder, any lifetime history of suicide attempt, or with suicidal ideation or behavior within 1 month prior to screening.
• Patient Health Questionnaire score >15 or any suicidal ideation of type 4 or type 5 on the Columbia-Suicide Severity Rating Scale
• Monogenic or syndrome obesity, and endocrine causes of obesity (such as untreated hypothyroidism or Cushing's syndrome), and obesity caused by medications that cause weight gain
• Prior bariatric surgery or weight loss devices unless removed for ≥1 year prior to screening for this study.
• Diagnosis of diabetes requiring current use of any antidiabetic drug or HbA1c ≥6.5% Note: Metabolic syndrome is not an exclusion, even if managed with an anti-diabetic drug such as metformin or an SGLT2 inhibitor. A diagnosis of prediabetes or impaired glucose tolerance managed with antidiabetic medication or non-pharmacologic approaches (e.g., diet and exercise) is not an exclusion as long as other study criteria are met and the patient has not progressed to a diagnosis of diabetes.
• Creatine kinase >1.5x ULN
• Any condition that is exclusionary for use of semaglutide (generally WEGOVY) in the patient. See the WEGOVY Prescribing Information. The following contraindications are listed in the WEGOVY prescribing information:
• Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
• Known hypersensitivity to semaglutide or any of the excipients in WEGOVY.
• Subjects with active or untreated malignancy within 5 years of screening (NOTE: treated non-melanoma skin cancers are allowable).
• Male subjects with a lifetime history of malignant prostate disease, such as prostate cancer.
• Male subjects with a PSA ≥4 ng/mL
• Patients with prior tendon rupture or those taking concomitant medications that increase the risk of tendon rupture (e.g., fluroquinoline antibiotics, bempedoic acid, or chronic use of systemic corticosteroids).
• Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg). NOTE: blood pressure may be retested as per the investigator criteria as needed.
• Patients with a resting heart rate ≥100 beats per minute. NOTE: heart rate may be retested as per the investigator criteria as needed.
• Patients that have received a GLP-1 Receptor Agonist (e.g., semaglutide) or a GIP/GLP-1 Receptor agonist (e.g., tirzepatide) within 12 months of Screening.
• Patients that wear foreign objects, at the discretion of the DXA technician, that cannot be removed at the time of DXA that could cause artifacts and decrease accuracy of exam, such as waist beads (e.g., for religious purposes).