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

A Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy of TLC-2716 in Subjects With Hypertriglyceridemia and Nonalcoholic Fatty Liver Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertriglyceridemia; Nonalcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: TLC-2716 Dose 1; Drug: TLC-2716 Dose 2

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ryan Huss, MD; Phone Number: 650-382-2225; Email: Clinicaltrials_Inquires@orsobio.com

Study Locations

• Mexico
  • Ciudad de México, Mexico, 06700
    • Recruiting
    • OrsoBio Research Site
  • Ciudad de México, Mexico, 14080
    • Recruiting
    • OrsoBio Research Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 45116
      • Recruiting
      • OrsoBio Research Site
    • Zapopan, Jalisco, Mexico, 45170
      • Recruiting
      • OrsoBio Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Oral dose of placebo-to-match	Drug: Placebo; Capsules administered orally
Experimental: TLC-2716 Dose 1; Oral dose of TLC-2716 Dose 1	Drug: TLC-2716 Dose 1; Capsules administered orally
Experimental: TLC-2716 Dose 2; Oral dose of TLC-2716 Dose 2	Drug: TLC-2716 Dose 2; Capsules administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fasting triglycerides	Relative (%) change in fasting triglycerides at Week 4 from baseline	Through study completion, up to Day 28 of the study
Incidence of TLC-2716 treatment-emergent adverse events	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.	Through study completion, up to Day 28 of the study

Collaborators and Investigators

• Sponsor: OrsoBio, Inc
• Investigators: Study Director: OrsoBio Study Director, OrsoBio, Inc

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Digestive System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypertriglyceridemia
• Other Study ID Numbers: 2716-CL-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No