Obesity & Overweight
Conditions
Brief summary
This is a phase 2 randomized, double-blind, placebo-controlled, multi-center study evaluating the efficacy and safety of LUM-201 plus Semaglutide versus Semaglutide plus placebo in obese adults with body mass index between 30 and 45 kg/m\^2, between the ages of 60 and 85 years that have mild functional impairment.
Interventions
DRUGLUM-201
Daily (AM) oral Tablet at 25 mg
DRUGPlacebo
Daily (AM) oral Tablet
DRUGSemagludtide
Daily (AM) oral Tablet
Sponsors
Lumos Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
60 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* Have Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM). * Have laboratory evidence diagnostic of diabetes mellitus during screening. * Have history of diabetic ketoacidosis or hyperosmolar state/coma within 6 months prior to screening. * Have a history of severe hypoglycemia. * Have a BMI \> 45 kg/m2 or weight \> 159 kg (350 lbs.). * Have a self-reported change in body weight \> 5 kg (11 lbs.) within 3 months prior to 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 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 serum calcitonin concentration \> 35 pg/mL at screening. * Have a history of prior or planned surgical treatment for obesity. * Have uncontrolled hypertension with systolic blood pressure (SBP) ≥ 150 mm Hg and/or diastolic blood pressure (DBP) ≥ 95 mm Hg. * 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 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 an estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2. * Have a known clinically significant gastric emptying abnormality. * Have a history of chronic or acute pancreatitis, or severe gastroesophageal reflux disease and symptomatic cholelithiasis with intact gallbladder. * Have serum lipase and/or amylase above 1.5 × the upper limit of normal (ULN). * 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 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 untreated or uncontrolled hypothyroidism or hyperthyroidism. * 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. * 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. * Have any hematological condition that may interfere with HbA1c measurement (for example, hemolytic anemias, sickle cell disease). * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants with Short Physical Performance Battery (SPPB) score ≤ 7 at Week 26. | From Day 1 to week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline to Week 26 in total body fat mass (kg) measured by dual-energy X-ray absorptiometry (DEXA). | Day 1 to week 26. | — |
| Change from baseline to Week 26 in total lean mass (kg) measured by dual-energy X-ray absorptiometry (DEXA). | Day 1 to week 26. | — |
| Change from baseline to Week 26 in fat-free mass (kg) measured by dual-energy X-ray absorptiometry (DEXA). | Day 1 to week 26. | — |
| Change from baseline to Week 26 in body weight (kg). | Day 1 to week 26. | — |
| Change from baseline to Week 26 in waist:hip ratio. | Day 1 to week 26. | — |
| Change from baseline to Week 26 in waist:height ratio. | Day 1 to week 26. | — |
| Assess safety and tolerability of LUM-201 in the presence of semaglutide. | Day 1 to week 26 | Incidence of treatment emergent adverse events, adverse events (AEs), and serious adverse events (SAEs). Clinically significant changes from Baseline to Week 26 in safety evaluations. |
| Change from Baseline to Week 26 in Individual Short Physical Performance Battery (SPPB) Test. | Day 1 to week 26 | — |
| Difference in proportions of participants achieving a clinically meaningful positive Short Physical Performance Battery (SPPB) change (1-point). | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in mean Short Physical Performance Battery (SPPB). | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Stair Climb (Power/Time). | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in 6 Minute Walk Test (6MWT). | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Grip Strength in kg using a hand dynamometer. | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Knee extension. | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Patient reported Outcome (PRO) questionnaire Short Form-36 (SF-36) score. | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Patient reported Outcome (PRO) questionnaire Impact of Weight on Quality of Life-Lite (IWQoL-Lite) score. | Day 1 to week 26 | — |
| Change from Baseline to Week 26 in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue measurements score. | Day 1 to week 26 | — |
Contacts
CONTACTLumos Pharma
Outcome results
None listed