AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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This is a Phase 1b multi-center, randomized, double-blind, dose-ranging, placebo-controlled, adaptive study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) of TERN-201 in patients with non-cirrhotic NASH.

Official Title
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A Multi-Center, Randomized, Double-Blind, Dose-Ranging, Placebo-Controlled, Proof of Concept, Adaptive, Phase 1b Clinical Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Orally Administered TERN-201 in Patients With Presumed Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH)

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: TERN-201
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 based on clinical characteristics or prior liver biopsy ALT ≥ 43 IU/L for men and ≥ 28 IU/L for women MRI-cT1 value> 800 ms Written informed consent Exclusion Criteria: History or clinical evidence of chronic liver diseases other than NAFLD History or clinical evidence of cirrhosis, hepatic decompensation or other severe liver impairment History of liver transplant, or current placement on a liver transplant list Weight loss of > 5% total body weight within 3 months prior to Screening Note: Other protocol-defined inclusion/exclusion 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: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: TERN-201 dose level 1<br>Orally administered. | Drug: TERN-201<br>* Investigational drug<br>|
| Placebo Comparator: Part 1: Placebo<br>Orally Administered | Other: Placebo<br>* Matching placebo<br>|
| Experimental: Part 2: TERN-201 dose level 2<br>Orally administered | Drug: TERN-201<br>* Investigational drug<br>|
| Placebo Comparator: Part 2: 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 |
| --- | --- | --- |
| Subject incidence of adverse events for TERN-201 versus placebo |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of TERN-201- AUC | Area under the curve | 12 weeks | 
| Plasma concentration of TERN-201- Cmax | Maximum observed concentration | 12 weeks | 
| Plasma concentration of TERN-201- Tmax | Time to reach maximum measured plasma concentration | 12 weeks | 
| Plasma concentration of TERN-201- T1/2 | Determination of half-life | 12 weeks | 
| Percent Change from baseline in plasma VAP-1/SSAO activity |  | 12 weeks | 
| Urine concentration of TERN-201- CLr | Renal clearance | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular adhesion protein-1(VAP-1)/ semicarbazide-sensitive amine oxidase (SSAO), Nonalcoholic steatohepatitis (NASH), Nonalcoholic Fatty Liver Disease (NAFLD)