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

Study Overview
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Brief Summary
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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)

Official Title
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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)

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: TERN-501
* Drug: TERN-101
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |  | 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 |  | 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 |  | 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 |  | 12 weeks | 
| Patient incidence of treatment emergent adverse events for all treatment groups |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nonalcoholic steatohepatitis (NASH), FXR agonist, Nonalcoholic Fatty Liver Disease (NAFLD), THR-β agonist