A Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy of TLC-2716 in Subjects With Hypertriglyceridemia and Nonalcoholic Fatty Liver Disease
Overview
- Phase
- Phase 2
- Intervention
- TLC-2716 Dose 2
- Conditions
- Hypertriglyceridemia
- Sponsor
- OrsoBio, Inc
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Incidence of TLC-2716 treatment-emergent adverse events
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief 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.
Detailed Description
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. Participation in the study can last up to approximately 10 weeks, including a 4 week Screening period, a 4-week treatment period during which study drugs will be administered, and a 2-week follow-up period.
Investigators
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.
Arms & Interventions
TLC-2716 Dose 2
Oral dose of TLC-2716 Dose 2
Intervention: TLC-2716 Dose 2
TLC-2716 Dose 1
Oral dose of TLC-2716 Dose 1
Intervention: TLC-2716 Dose 1
Placebo
Oral dose of placebo-to-match
Intervention: Placebo
Outcomes
Primary Outcomes
Incidence of TLC-2716 treatment-emergent adverse events
Time Frame: Through study completion, up to Day 28 of the study
Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related.
Change in fasting triglycerides
Time Frame: Through study completion, up to Day 28 of the study
Relative (%) change in fasting triglycerides at Week 4 from baseline