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

NCT06564584 | Recruiting Phase 2

• 1 other identifier: 2716-CL-102
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

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.

Conditions

Hypertriglyceridemia; Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (3)

TLC-2716 Dose 1

EXPERIMENTAL

Oral dose of TLC-2716 Dose 1

Drug: TLC-2716 Dose 1

TLC-2716 Dose 2

EXPERIMENTAL

Oral dose of TLC-2716 Dose 2

Drug: TLC-2716 Dose 2

Placebo

PLACEBO COMPARATOR

Oral dose of placebo-to-match

Drug: Placebo

Interventions

TLC-2716 Dose 1 DRUG

Capsules administered orally

TLC-2716 Dose 1

TLC-2716 Dose 2 DRUG

Capsules administered orally

TLC-2716 Dose 2

Placebo DRUG

Capsules administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• OrsoBio, Inc: lead

Study Sites (4)

OrsoBio Research Site

Guadalajara, Jalisco, 45116, Mexico

RECRUITING

OrsoBio Research Site

Zapopan, Jalisco, 45170, Mexico

RECRUITING

OrsoBio Research Site

Mexico City, Mexico City, 06700, Mexico

RECRUITING

OrsoBio Research Site

Mexico City, Mexico City, 14080, Mexico

RECRUITING

MeSH Terms

Conditions

Hypertriglyceridemia; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• OrsoBio Study Director

  OrsoBio, Inc

  STUDY DIRECTOR

Central Study Contacts

Ryan Huss, MD

CONTACT

650-382-2225; Clinicaltrials_Inquires@orsobio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 21, 2024
• Study Start: August 12, 2024
• Primary Completion: June 1, 2025
• Study Completion: September 1, 2025
• Last Updated: April 3, 2025

Record last verified: 2024-08

Locations

ME (4)