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

Launched by ORSOBIO, INC · Aug 19, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called TLC-2716 to see if it is safe, tolerable, and effective for people with high triglycerides (a type of fat in the blood) and nonalcoholic fatty liver disease (NAFLD). The trial will measure changes in triglyceride levels and liver fat using MRI scans, along with other health markers. Participants will be randomly assigned to receive either the medication or a placebo (a non-active treatment), and they will be closely monitored throughout the study.

To be eligible for this trial, participants must be adults aged 18 to 75 with a body mass index (BMI) of 28 or higher and elevated triglycerides of 350 mg/dL or more. They should not have diabetes or should have controlled diabetes. Participants will be required to avoid significant weight loss and certain medications before the trial. Those who join can expect regular check-ups and tests to track their health, and they will be guided on what to do before and during the study. It's important to note that the trial is currently recruiting participants, so interested individuals should talk to their doctor for more information.

Gender

ALL

Eligibility criteria

• 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