Evaluating the Efficacy and Safety of LUM-201 Plus Semaglutide Versus Semaglutide Plus Placebo in Older Obese Adults

Prior treatment

• Have history of diabetic ketoacidosis or hyperosmolar state/coma within 6 months prior to screening.
• Have a self-reported change in body weight \> 5 kg (11 lbs.) within 3 months prior to screening.
• Have a history of prior or planned surgical treatment for obesity.
• Have any of the following within last 6 months prior to screening: NYHA Functional Classification I-IV heart failure, myocardial infarction, angina, coronary artery bypass graft, percutaneous coronary intervention, transient ischemic attack, stroke, or decompensated congestive heart failure.
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within the past 5 years prior to screening.
• Have had a transplanted organ (corneal transplants \[keratoplasty\] allowed) or awaiting an organ transplant.
• Are receiving or have received within 3 months prior to screening chronic (\> 2 weeks or 14 days) systemic glucocorticoid therapy or have evidence of a significant active autoimmune abnormality that has required treatment within the last 3 months.
• Have current or recent treatment with medications and/or supplements that may cause significant weight gain.
• Currently receiving or planning to initiate during the study any muscle toning or body contouring treatments such as high-intensity focused electromagnetic therapy, or neurotoxin injections targeting large muscle groups (for example, trapezius, gastrocnemius) for slimming or relaxation purposes.
• Have taken within 3 months prior to randomization, medications (prescribed or over-the counter) or alternative remedies intended to promote weight loss.
• Have started implantable or injectable contraceptives (such as Depo-Provera®) within 6 months prior to screening.
• Documented moderate to severe obstructive sleep apnea (unless controlled by medically prescribed intervention for at least 3 months prior to screening).
• Prior treatment with growth factors including, but not limited to, GH, IGF-1, and GH secretagogues.

Other illness

• Have Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM).
• Have a history of severe hypoglycemia.
• Have any other condition not listed in this section (for example, hypersensitivity or intolerance) that is a contraindication to GLP-1 receptor agonist or dual GLP-1/GIP receptor agonist.
• Have uncontrolled hypertension with systolic blood pressure (SBP) ≥ 150 mm Hg and/or diastolic blood pressure (DBP) ≥ 95 mm Hg.
• Have a history of chronic or acute pancreatitis, or severe gastroesophageal reflux disease and symptomatic cholelithiasis with intact gallbladder.
• Have a history of hepatic disorders including cirrhosis or other hepatic disorder other than metabolic-associated fatty liver disease (MAFLD), or nonalcoholic fatty liver disease.
• Have active hepatitis B or C virus at screening. Have known positive history of human immunodeficiency virus. Have an active Coronavirus Disease 2019 at screening.
• Have obesity induced by other endocrinologic disorders.
• Have a history of significant active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder within the last 2 years.
• Have any lifetime history of a suicide attempt.
• Have a family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

Lab values

• Have laboratory evidence diagnostic of diabetes mellitus during screening.
• Have received prior exposure to a GLP-1 receptor agonist (including dual GLP-1/ GIP receptor agonists\]) within 180 days before screening, any other anti-obesity medication, glucose-lowering agent (non-GLP-1), or glucose lowering supplements such as berberine, etc. within 90 days before screening.
• Have serum calcitonin concentration \> 35 pg/mL at screening.
• Mean QTcF (Fridericia \[QTcF=QT/RR1/3\]) interval \> 450 ms (male) or \> 470 ms (female) on triplicate ECGs.
• Have fasting triglyceride \> 500 mg/dL.
• Have an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2.
• Have serum lipase and/or amylase above 1.5 × the upper limit of normal (ULN).
• Have an impaired liver function, defined as screening aspartate aminotransferase (AST) \> 2.5 × ULN, or alanine aminotransferase \> 2.5 × ULN, or total bilirubin level \> 1.2 × ULN (except for cases of known Gilbert's Syndrome).
• Alkaline phosphatase (ALP) level \> 1.5 × ULN.
• Have any hematological condition that may interfere with HbA1c measurement (for example, hemolytic anemias, sickle cell disease).

Other

• Have a BMI \> 45 kg/m2 or weight \> 159 kg (350 lbs.).
• Have a known clinically significant gastric emptying abnormality.
• Have untreated or uncontrolled hypothyroidism or hyperthyroidism.

• Be willing to provide written informed consent to participate in this study.
• Males or females, aged ≥ 60 to \< 85 years.
• Have a BMI ≥ 30 kg/m2.
• SPPB score at the screening visit ≥ 7 to ≤ 9.
• Have a history of ≥ 1 self-reported unsuccessful dietary effort to lose weight.
• Female participants must be postmenopausal, confirmed by an follicle stimulating hormone (FSH) level ≥ 25 IU/L.
• Male participants must be able to comply with contraception requirements.
• Must agree to refrain from any reconstructive and/or cosmetic surgery and/or non-invasive cosmetic procedure that may affect body weight during the study such as mammoplasty, lipoplasty, non-invasive adipose and/or cellulite treatment devices.
• Must refrain from scheduling any elective surgery and/or other invasive or non-invasive procedures during the study unless medically warranted.