DUET Study: A Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2a Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy as Well as in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (NASH)

This is a Phase 2a Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy as well as in Combination with TERN-101 in Noncirrhotic Adults with Presumed Non-Alcoholic Steatohepatitis (NASH)

Study Overview

• Status: Completed
• Conditions: NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Other: Placebo; Drug: TERN-501; Drug: TERN-101

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Site 1017: The Institute for Liver Health dba Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • Site 1018: Arizona Liver Health
  • California
    • Coronado, California, United States, 92118
      • Site 1004 Southern California Research Center
    • Gardena, California, United States, 90247
      • Site 1061 Velocity Clinical Research, Gardena
    • La Jolla, California, United States, 92037
      • Site 1013 University of California, San Diego - Altman Clinical and Translational Research Institute
    • Los Angeles, California, United States, 90036
      • Site 1016 Ruane Clinical Research Group Inc.
    • Montclair, California, United States, 91763
      • Site 1060 Catalina Research Institute, LLC
    • Panorama City, California, United States, 91402
      • Site 1001 National Research Institute
    • Rialto, California, United States, 92377
      • Site 1040 Inland Empire Clinical Trials, LLC
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Site 1062 Excel Medical Clinical Trials, LLC
    • Doral, Florida, United States, 33122
      • Site 1057:Integrity Clinical Research, LLC
    • Lakewood Ranch, Florida, United States, 34211
      • Site 1041: Florida Research Institute
    • Miami, Florida, United States, 33125
      • Site 1058 Optimus U Corporation
    • Miami, Florida, United States, 33136
      • Site 1036 Schiff Center for Liver Diseases / University of Miami
    • Miami, Florida, United States, 33136
      • Site 1045 University of Miami Hospital & Clinics, Sylvester Comp. Cancer Center
    • Miami Lakes, Florida, United States, 33016
      • Site 1007: Floridian Clinical Research, LLC
    • Port Orange, Florida, United States, 32127
      • Site 1055: Progressive Medical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site 1032 IU Health University Hospital
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Site 1052: Iowa Diabetes and Endocrinology Research Center
  • Louisiana
    • Shreveport, Louisiana, United States, 71105
      • Site 1054 Louisiana Research Center
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Site 1063 GI Alliance - Flowood
  • North Carolina
    • Morehead City, North Carolina, United States, 28557
      • Site 1042: Lucas Research, Inc
  • Tennessee
    • Clarksville, Tennessee, United States, 37040
      • Site 1059: Premier Medical Group
    • Nashville, Tennessee, United States, 37211
      • Site 1044: Quality Medical Research
  • Texas
    • Arlington, Texas, United States, 76012
      • Site 1005:Texas Clinical Research Institute, LLC
    • Austin, Texas, United States, 78757
      • Site 1050: Pinnacle Clinical Research
    • Edinburg, Texas, United States, 78539
      • Site 1051: South Texas Research Institute
    • Houston, Texas, United States, 77030
      • Site 1043 Liver Specialists of Texas
    • Houston, Texas, United States, 77030
      • Site 1046 Houston Methodist Hospital
    • Houston, Texas, United States, 77079
      • Site 1039: Houston Research Institute
    • San Antonio, Texas, United States, 78215
      • Site 1003: Clinical Trials of Texas, LLC
    • San Antonio, Texas, United States, 78215
      • Site 1006: American Research Corporation
    • San Antonio, Texas, United States, 78229
      • Site 1056: Pinnacle Clinical Research
  • Virginia
    • Richmond, Virginia, United States, 23236
      • Site 1053 Bon Secours Richmond Community Hospital LLC d/b/a Bon Secours Liver Institute of Richmond
  • Washington
    • Seattle, Washington, United States, 98105
      • Site 1022 Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female, 18 to 75 years of age
• Overweight or obese with a body mass index (BMI) ≥ 25 kg/m2
• Presumed NASH diagnosed by prior biopsy and/or imaging criteria
• Written informed consent

Key Exclusion Criteria:

• History or clinical evidence of chronic liver diseases other than NAFLD
• History or known clinical evidence of cirrhosis, esophageal varices, hepatic decompensation or other severe liver impairment,
• History of liver transplant, or current placement on a liver transplant list
• Current diagnosis or history of pituitary or thyroid disorders - except for patients with primary hypothyroidism on a stable dose of thyroid hormone replacement therapy.
• Abnormal TSH or free T4 levels
• Weight loss of > 5% total body weight within 3 months prior to Screening
• Uncontrolled diabetes
• Uncontrolled hyperlipidemia
• Unstable cardiovascular disease
• Excessive alcohol consumption

Other protocol-defined I/E criteria that apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: TERN-501 1 mg; Orally administered.	Drug: TERN-501; Investigational drug
Experimental: Arm 2: TERN-501 3 mg; Orally administered.	Drug: TERN-501; Investigational drug
Experimental: Arm 3: TERN-501 6 mg; Orally administered.	Drug: TERN-501; Investigational drug
Experimental: Arm 4: TERN-501 3 mg + TERN-101 10 mg; Orally administered.	Drug: TERN-501; Investigational drug; Drug: TERN-101; Investigational drug
Experimental: Arm 5: TERN-501 6 mg + TERN-101 10 mg; Orally administered.	Drug: TERN-501; Investigational drug; Drug: TERN-101; Investigational drug
Experimental: Arm 6:TERN-101 10 mg; Orally administered.	Drug: TERN-101; Investigational drug
Placebo Comparator: Arm 7: Matching placebo; Orally administered.	Other: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Change From Baseline in MRI-PDFF at Week 12 for TERN-501 Monotherapy (Arms 1, 2 and 3) Compared to Placebo.	Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) is a non-invasive imaging technique that measures fat content in tissue, particularly in the liver. Relative change from baseline is calculated for each subject as 100 x [(Week 12 Value - Baseline Value)/Baseline Value].	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in cT1 Relaxation Time at Week 12 for TERN-501 Monotherapy (Arms 1, 2 and 3) Compared to Placebo	Corrected T1 (cT1) is a quantitative MRI relaxation parameter that measures liver inflammation and fibrosis. Change from baseline is calculated for each subject as (Week 12 Value - Baseline Value).	12 weeks
Relative Change From Baseline in MRI-PDFF at Week 12 for TERN-501+TERN-101 Combination (Arms 4 and 5) Compared to Placebo	Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) is a non-invasive imaging technique that measures fat content in tissue, particularly in the liver. Relative change from baseline is calculated for each subject as 100 x [(Week 12 Value - Baseline Value)/Baseline Value].	12 weeks
Change From Baseline in cT1 Relaxation Time at Week 12 for TERN-501+TERN-101 Combination (Arms 4 and 5) Compared to Placebo	Corrected T1 (cT1) is a quantitative MRI relaxation parameter that measures liver inflammation and fibrosis. Change from baseline is calculated for each subject as (Week 12 Value - Baseline Value).	12 weeks
Number and Percentage of Participants With Any Treatment Emergent Adverse Event for All Treatment Groups (Threshold of 0%)	This outcome measures the number and percentage of participants with any Treatment Emergent Adverse Event (TEAE) for All Treatment Groups (0% Threshold). TEAEs by System Organ Class and Preferred Term meeting the 5% Threshold are reported in the Other Adverse Events section.	16 weeks

Collaborators and Investigators

• Sponsor: Terns, Inc.
• Investigators: Study Director: Study Director, Terns, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2022
• Primary Completion (Actual): July 10, 2023
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Nonalcoholic steatohepatitis (NASH); FXR agonist; Nonalcoholic Fatty Liver Disease (NAFLD); THR-β agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: TERNCB-2002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No