Clinical Trials

Inclusion Criteria:

• Participant must be 18 to 75 years of age inclusive, at the time of signing the informed consent
• 2. Male and/or female, must be willing to follow the contraception requirements defined by the study protocol (Appendix 10)
  • Female participants of childbearing potential must also have negative pregnancy tests at screening and on Day 1 (prior to Randomization), not be breastfeeding, and not plan to become pregnant or donate eggs (oocytes) during the study or within 30 days after the last dose of study drug
  • Male participants must be willing not to donate sperm from the first dose of study drug until 90 days after the last dose of study drug.
• Must have a body mass index (BMI) at Screening and on Day 1 (prior to Randomization) of:
  • ≥ 30 kg/m2 to < 50 kg/m2 OR
  • ≥ 27 kg/m2 to 30 years of age)
    • Hypertension: on BP-lowering medication or SBP ≥ 130 mmHg or DBP ≥80 mmHg at Screening
    • Dyslipidemia: on lipid-lowering medication or having LDL ≥ 160 mg/dL or TG ≥ 150 mg/dL or HDL 30 years of age)
    • Cardiovascular disease: NYHA Functional Classification Class I-II heart failure
    • Obstructive sleep apnea (only in participants > 30 years of age)
• Must have self-reported stable body weight for at least 3 months prior to Screening and prior to Randomization (<5% body weight gain or loss)
• Must have an HbA1c < 6.5% at Screening
• Capable of giving signed informed consent as described in Section 10.1.2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

• Have any prior diagnosis of type 1 or type 2 diabetes mellitus (T1DM or T2DM) or rare forms of diabetes mellitus.

Note: Participants with gestational diabetes that resolved >3 years ago (and no current evidence of diabetes mellitus) may be enrolled in the study

• Have any laboratory value suggestive of diabetes mellitus during Screening, including any of the following:
  • HbA1c ≥ 6.5% (48 mmol/mol),
  • Fasting glucose ≥ 126 mg/dL (7.0 mmol/L), or
  • Random glucose ≥ 200 mg/dL (11.1 mmol/L)
• Have had or are planning surgical treatment for obesity, including but not limited to gastric bypass or restrictive bariatric surgery (eg, Lap-Band);
  • Prior history of liposuction or abdominoplasty are allowed, if performed >1 year prior to Screening
  • Prior treatment with reversible gastric devices (eg, Lap-Band) are allowed if removed >1 year prior to Screening
• Have obesity induced by other diagnosed endocrinologic disorders (eg, Cushing’s Syndrome, hypogonadism, growth hormone deficiency, hypothalamic disorder, etc) or diagnosed with monogenetic or syndromic forms of obesity (eg, Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome) Note: polycystic ovarian syndrome and/or stable/well-controlled hypothyroidism are allowed
• Have had or are planning endoscopic and/or device-based therapy for obesity; or have had an obesity-related device removed within the last 12 months prior to Screening. Excluded endoscopic and/or device-based therapies for obesity include but not limited to:
  • Mucosal ablation
  • Gastric artery embolization
  • Intragastric balloon
  • Duodenal-jejunal endoluminal liner
• Obesity induced by medication
• Prior treatment with anti-obesity medications (including, but not limited to, GLP-1RAs including compounded GLP-1RAs) or participation in a medical weight loss program within 3 months prior to Screening.
• Have renal impairment, measured as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 , calculated by Chronic Kidney Disease-Epidemiology (CKD-EPI, 2021 equation) at Screening.
• Have a known clinically significant gastric emptying abnormality (eg, severe gastroparesis or gastric outlet obstruction) or regularly take drugs that directly affect GI motility.
• Have a history of acute or chronic pancreatitis.
• Have a history of significant active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (eg, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years (MDD that is controlled and stable for > 2 years, in the opinion of the Investigator, is allowed).
• Have a lifetime history of suicide attempt.
• Have a Patient Health Questionnaire-9 (PHQ-9) score of 15 or more at Screening or prior to Randomization.
• On the C-SSRS at Screening and prior to Randomization:
  • A ‘yes’ answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the “Suicidal Ideation” portion of the C-SSRS OR
  • A “yes” answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the “Suicidal Ideation” portion of the C-SSRS OR
  • A “yes” answer to any of the suicide-related behaviors (actual attempt [see Exclusion Criterion #12], interrupted attempt, aborted attempt, preparatory act, or behavior) on the “Suicidal Behavior” portion of the C-SSRS AND
  • The ideation or behavior occurred within the past month.
• Have poorly controlled hypertension (ie, supine systolic BP ≥160 mmHg or supine diastolic BP ≥100 mmHg) at Screening, renal artery stenosis, or evidence of labile BP including symptomatic postural hypotension. Participants on antihypertensive medications must be on a stable dose for at least 3 months prior to Screening.

Note: If a single BP measurement demonstrates an SBP ≥160 mmHg or DBP ≥100 mmHg, the BP measurement can be repeated two times more and the average of the 3 BP values used to determine eligibility at Screening.

• Have an elevated resting pulse rate (PR) (>100 bpm) at Screening.
• Have experienced any of the following cardiovascular conditions within 6 months prior to Screening:
  • Acute myocardial infarction
  • Cerebrovascular accident (stroke)
  • Transient ischemic attack (stroke symptoms that rapidly resolved)
  • Unstable angina
  • Congestive heart failure (CHF) requiring hospitalization.
• Ongoing or history of frequent, intermittent or chronic tachyarrhythmia syndromes (such as atrial fibrillation, supraventricular tachycardia, and positional orthostatic tachycardia syndrome [POTS]).

Note: Participants with history of premature atrial contractions or premature ventricular contractions may be included in the study.

• Have a history of NYHA Functional Classification III or IV CHF.
• Have an electrocardiogram (ECG) with abnormalities at Screening which are considered by the Investigator to potentially interfere with the interpretation of changes in ECG intervals.
• HaHave a personal or family history of long QT syndrome, family history of sudden death in a first-degree relative (parents, siblings, or children) before the age of 40 years, or a personal history of unexplained syncope within the last year.

Note: Chronic use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval at Screening is exclusionaryve a mean QTcF of > 450 msec (male) or > 470 msec (female) at Screening.

• Have a history of clinically significant gallbladder disease and/or choledocholithiasis (gallstones)

Note: Participants with cholecystectomy may be included in the study

• Have signs and symptoms of any liver disease other than metabolic dysfunctionassociated steatotic liver disease, or have any of the following at Screening:
  • ALT or AST level >3.0× ULN for the reference range
  • ALP level >1.5× ULN for the reference range
  • TBL >1.5× ULN for the reference range (except for cases of known Gilbert’s Syndrome)
  • TBL between 1× ULN and 1.5× ULN and direct bilirubin > ULN for the reference range.
• . Have evidence of hypothyroidism or hyperthyroidism based on clinical evaluation and/or an abnormal thyroid-stimulating hormone (TSH) that, in the opinion of the Investigator, would pose a risk to participant safety. Subjects on a stable dose of thyroid replacement therapy for at least 3 months prior to Screening who are clinically euthyroid and who are anticipated to remain on the same dose through the trial period may be eligible if they meet other criteria.
• Have a known personal or family history (first degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma.
• Have a serum calcitonin level at Screening of ≥ 20 ng/L.
• Have a history or evidence, in the opinion of the Investigator, of a significant uncontrolled endocrine abnormality (eg, thyrotoxicosis or adrenal crises)
• Have a history of an active or untreated malignancy, or are in remission of a clinically significant malignancy (ie, malignancy other than basal or squamous cell skin cancer, in situ carcinoma of the cervix, ductal carcinoma in situ [DCIS] of the breast, or in situ prostate cancer, eg, high-grade prostatic intraepithelial neoplasia [PIN]) for less than 5 years).
• Have evidence of human immunodeficiency virus (HIV) and/or positive HIV antibodies historically or as evidenced from laboratory results collected at Screening.
• Evidence of hepatitis B and/or positive hepatitis B surface antigen.
• Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA or positive hepatitis C antibody (anti-HCV). Participants treated for hepatitis C (and diagnosed as cured) must have a negative RNA test at Screening, AND also be documented as RNA negative for at least 3 years prior to Screening to be eligible for the study.
• Have a history of any other condition (such as known drug or alcohol abuse, diagnosed eating disorder, or other serious psychiatric disorder) that, in the opinion of the Investigator, may preclude the participant from following and completing the protocol.
• Have an average weekly alcohol intake that exceeds 14 units per week (males) or 7 units per week (females) [1 unit = 12 oz or 260 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits]
• Have a history of use of illicit drugs, marijuana or tetrahydrocannabinol (THC)- containing products within 3 months of enrollment and/or unwillingness to abstain from illicit drugs, marijuana or THC-containing products during the trial.
• Have had a transplanted organ (other than corneal transplants [keratoplasty], which are allowed) or are awaiting organ transplant.
• Have had any exposure to GLP-1 analogs, GLP-1 receptor agonists (including dual GLP-1/GIP receptor agonists) or other related compounds within the prior 3 months; this includes compounded drugs.

Note: Participants who previously took GLP-1 analogs or related compounds and who discontinued those medications for intolerability or lack of efficacy should not be randomized

• Have any prior history of hypersensitivity/allergies to GLP-1 analogs or excipients of TERN-601.
• Have given a blood donation of ≥ 500 mL within 8 weeks prior to Screening, or had a blood transfusion or severe blood loss within the prior 3 months, or have known autoimmune or congenital anemia (eg, hemolytic anemia, sickle cell anemia), or have a hemoglobin value < 11 g/dL (males) or <10 g/dL (females)
• Triglycerides > 500 mg/dL (5.7 mmol/L); if participant is on lipid-lowering therapy, must be on stable dose(s) for ≥ 3 months prior to Screening.
• Have evidence of significant active gastrointestinal disease, prior gastrointestinal surgery, or gastrointestinal symptoms (eg, abdominal pain, nausea, vomiting, diarrhea, constipation) which could alter study drug absorption and/or interpretation of key gastrointestinal safety and tolerability signals.
• Have evidence of a significant active, uncontrolled medical condition, or a history of any medical problem capable of constituting a risk when taking the study drug or interfering with the interpretation of data, as judged by the Investigator at Screening.
• Have evidence of a significant active autoimmune abnormality (eg, lupus or rheumatoid arthritis) that, in the opinion of the Investigator, is likely to require concurrent treatment with systemic glucocorticoids in the next 9 months.
• Have difficulty swallowing tablets.
• Unless otherwise specified, all concomitant medications should be at a stable dose for ≥ 3 months prior to Screening and Randomization.
• Are receiving or have received within 3 months prior to Screening, chronic (> 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, single intraarticular injection, or inhaled preparations)
• Have current treatment with or history of treatment with (within 3 months prior to Screening) medication that may cause significant weight gain, including but not limited to, tricyclic antidepressants, atypical antipsychotics, and mood stabilizers. However, participants at a stable dose (greater than 6 months and with no expectation that the dose will change within the next 6 months) and who are weight stable for the last 6 months on these medications may be included in the study (providing they meet all other entry criteria).
• Examples of medications causing weight gain that must be at stable doses for at least 6 months and with no expectation of changing within the next 6 months include:
  • imipramine ii
  • amitriptyline iii
  • mirtazapine
  • paroxetine
  • phenelzine
  • chlorpromazine
  • thioridazine
  • clozapine
  • valproic acid and its derivatives
  • lithium

Note: Selective serotonin reuptake inhibitors other than paroxetine are permitted

• Have taken within 3 months prior to Screening, medications (prescribed or over the counter) or alternative remedies (including herbal/nutritional supplements) intended to promote weight loss.
• Examples include, but are not limited to:
  • liraglutide ii. orlistat (prescription or OTC)
  • sibutramine
  • phenylpropanolamine
  • mazindol
  • phentermine, topiramate or phentermine/topiramate combination
  • lorcaserin
  • naltrexone/bupropion
  • semaglutide
  • tirzepatide
  • other similar body weight loss medication(s), including OTC or compounded medications
• Have taken metformin, or any other glucose-lowering medication, regardless of reason for prescription (eg, polycystic ovarian syndrome, diabetes prevention) within 3 months of Screening.
• Are currently taking or chronic use (>2 weeks) within 3 months prior to Screening a central nervous system stimulant (eg, Ritalin-SR®), with the exception of caffeinated beverages, at Screening.
• Are taking any medications that may result in a drug-drug interaction (see Section 6.6) within 30 days prior to Randomization.
• Evidence (in the opinion of the Investigator) of regular use of known drugs of abuse.
• Are currently enrolled in any other clinical study involving an investigational drug or any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have participated within the last 3 months in a clinical study and received treatment, whether active or placebo. If the study involved an investigational drug, at least 5 elimination half-lives or 3 months (whichever is longer) should have passed.
• Are, in the opinion of the Investigator or Sponsor, unsuitable for inclusion in the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 1/21/2025. Questions regarding updates should be directed to the study team contact.