NASH - Nonalcoholic Steatohepatitis
Conditions
Keywords
Vascular adhesion protein-1(VAP-1)/ semicarbazide-sensitive amine oxidase (SSAO), Nonalcoholic steatohepatitis (NASH), Nonalcoholic Fatty Liver Disease (NAFLD)
Brief summary
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.
Interventions
DRUGTERN-201
Investigational drug
OTHERPlacebo
Matching placebo
Sponsors
Terns, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Triple
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Incidence of Adverse Events for TERN-201 Versus Placebo | Day 1 through Week 16 | Number of patients experiencing at least 1 TEAE (Safety Analysis Set). TEAE = Treatment-emergent adverse event. Please see additional details in Adverse Events section. |
| Treatment-Emergent Laboratory Abnormalities | Day 1 through Week 16 | Number of patients with any worsening of ≥ 2 NCI CTCAE Grades in each laboratory assessment category. CTCAE = Common Terminology Criteria for Adverse Events; NCI = National Cancer Institute; laboratory abnormalities were classified according to NCI CTCAE, version 5, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-Threatening |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients who orally administered the Placebo | 17 |
| TERN-201 10mg Patients who orally administered 10mg of TERN-201 | 20 |
| TERN-201 20mg Patients who orally administered 20mg of TERN-201 | 15 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | TERN-201 10mg | TERN-201 20mg | Total |
|---|---|---|---|---|
| Age, Continuous | 59 years | 49 years | 48 years | 50.5 years |
| Age, Customized < 65 years | 13 Participants | 18 Participants | 13 Participants | 44 Participants |
| Age, Customized >= 65 years | 4 Participants | 2 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 14 Participants | 9 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 18 Participants | 10 Participants | 43 Participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 9 Participants | 35 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 20 | 0 / 15 |
| other Total, other adverse events | 9 / 17 | 11 / 20 | 8 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 20 | 0 / 15 |
Outcome results
Primary
Patient Incidence of Adverse Events for TERN-201 Versus Placebo
Number of patients experiencing at least 1 TEAE (Safety Analysis Set). TEAE = Treatment-emergent adverse event. Please see additional details in Adverse Events section.
Time frame: Day 1 through Week 16
Population: Safety Analysis Set consists of all patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Patient Incidence of Adverse Events for TERN-201 Versus Placebo | 9 Participants |
| TERN-201 10mg | Patient Incidence of Adverse Events for TERN-201 Versus Placebo | 11 Participants |
| TERN-201 20mg | Patient Incidence of Adverse Events for TERN-201 Versus Placebo | 8 Participants |
Primary
Treatment-Emergent Laboratory Abnormalities
Number of patients with any worsening of ≥ 2 NCI CTCAE Grades in each laboratory assessment category. CTCAE = Common Terminology Criteria for Adverse Events; NCI = National Cancer Institute; laboratory abnormalities were classified according to NCI CTCAE, version 5, Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-Threatening
Time frame: Day 1 through Week 16
Population: Safety Analysis Set consists of all patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Treatment-Emergent Laboratory Abnormalities | Hematology | 1 Participants |
| Placebo | Treatment-Emergent Laboratory Abnormalities | Fasting Lipids | 0 Participants |
| Placebo | Treatment-Emergent Laboratory Abnormalities | Serum Chemistry | 0 Participants |
| TERN-201 10mg | Treatment-Emergent Laboratory Abnormalities | Hematology | 1 Participants |
| TERN-201 10mg | Treatment-Emergent Laboratory Abnormalities | Serum Chemistry | 1 Participants |
| TERN-201 10mg | Treatment-Emergent Laboratory Abnormalities | Fasting Lipids | 0 Participants |
| TERN-201 20mg | Treatment-Emergent Laboratory Abnormalities | Fasting Lipids | 0 Participants |
| TERN-201 20mg | Treatment-Emergent Laboratory Abnormalities | Serum Chemistry | 1 Participants |
| TERN-201 20mg | Treatment-Emergent Laboratory Abnormalities | Hematology | 1 Participants |