Phase 2a Study of Safety, Tolerability, and Efficacy of TLC-2716 in Subjects With Hypertriglyceridemia and NAFLD

Summary

This is a Phase 2a, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of 2 dose levels of TLC-2716 in subjects with hypertriglyceridemia and nonalcoholic fatty liver disease as assessed by changes in fasting triglycerides, liver steatosis by MRI, and other biomarkers.

Eligibility

Inclusion Criteria:

* BMI ≥ 28 kg/m2 at Screening
* Fasting TG ≥ 350 mg/dL
* Subjects without diabetes or subjects with diabetes and HbA1c \< 9.5% at Screening
* Screening laboratory evaluations (eGFR, ALT, AST, INR, total bilirubin, platelet count) must fall within the protocol-defined ranges
* A clinical diagnosis of NAFLD/NASH within 5 years of Screening based on historical hepatic imaging (e.g., ultrasound, MRI, computed tomography \[CT\], or Controlled Attenuation Parameter \[CAP\] by vibration-controlled transient elastography ≥ 250 dB/m), and no documented weight loss \> 5% between the date of the historical hepatic imaging and Screening OR a historical liver biopsy within 5 years of Screening consistent with NAFLD/NASH without cirrhosis and no documented weight loss \> 5% between the date of the historical liver biopsy and Screening
* Normotensive subjects or subjects without uncontrolled hypertension, defined as systolic blood pressure \> 155 mmHg and/or diastolic blood pressure \> 90 mmHg at Screening
* A 12-lead electrocardiogram (ECG) at Screening that is normal or with abnormalities that are considered not clinically significant by the investigator
* Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 prior to first dose of study drug
* Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion Criteria:

* HbA1c ≥ 9.5% at Screening
* Weight loss \> 5% during the 90 days prior to Screening
* Pregnant or lactating subjects.
* Current alcohol abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
* Current substance abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
* A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody
* Medical history of liver disease other than NAFLD/NASH, including but not limited to, alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency.
* Any history of cirrhosis or decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding, or Child-Pugh-Turcotte score \> 6 at Screening
* Unstable cardiovascular disease
* History of intestinal resection or malabsorptive condition that may limit the absorption of study drug. Appendectomy and cholecystectomy are not exclusionary.
* Presence of severe peptic ulcer, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions at Screening, in the opinion of the investigator
* Any scheduled surgery during the trial period, excluding minor surgical procedures performed under local anesthesia, in the opinion of the investigator
* History of malignancy within 5 years prior to Screening except adequately treated carcinoma in situ of the cervix, and/or squamous cell cancer, or other localized non-melanoma skin cancer
* History of significant drug allergy, such as anaphylaxis or significant drug sensitivity, in the opinion of the investigator
* Known hypersensitivity to study drug, its metabolites, or formulation excipients
* Presence of any medical condition that could, in the opinion of the investigator, compromise the subject's ability to participate in the study, including a history of substance abuse or a psychiatric disorder, including any subject with a psychiatric hospital admission or emergency room visit in the 2 years prior to Screening
* Any laboratory abnormality that in the opinion of the investigator could adversely affect the safety of the subject or impair assessment of study results
* Medications or therapies prescribed or taken over-the-counter for weight loss, in the 90 days prior to Screening
* Receipt of vaccination for COVID-19 or any other live vaccine within 14 days of planned dosing of study drug

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Conditions3

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