Nonalcoholic Fatty Liver, Nonalcoholic Steatohepatitis
Conditions
Brief summary
This study is a Phase 1, first-in-human single-dose escalation and multiple dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of OA-235i in subjects with nonalcoholic steatohepatitis.
Detailed description
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a single ascending dose (SAD) in participants with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. This dose-escalating strategy will test the safety of OA-235i when given as a single subcutaneous dosage using up to five successive cohorts. Each cohort will have three non-randomized participants receiving the active medication. One (1) planned multiple dose (MD) randomized, placebo-controlled expansion cohort with 9 NAFLD/NASH subjects will be enrolled for a 7-day dosing regimen at a dose level to be determined from the SAD portion of the study.
Interventions
DRUGOA-235i (4 mg)
3 participants will receive 4 mg as a single subcutaneous dose
DRUGOA-235i (8 mg)
3 participants will receive 8 mg as a single subcutaneous dose
DRUGOA-235i (16 mg)
3 participants will receive 16 mg as a single subcutaneous dose
DRUGOA-235i (30 mg)
3 participants will receive 30 mg as a single subcutaneous dose
DRUGOA-235i (40 mg)
3 participants will receive 40 mg as a single subcutaneous dose
DRUGOA-235i or placebo
9 participants will receive a daily subcutaneous dose of OA-235i or placebo for 7 consecutive days
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mayo Clinic
Oasis Pharmaceuticals, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
All subjects will be blinded to IP dose/level in Phase 1a; subjects, Investigator and site staff (excluding unblinded pharmacy staff) will be blinded to IP/placebo in Phase 1b.
Intervention model description
Single ascending dose (SAD) sequential group study of a sc dose of OA-235i in five (5) planned dose cohorts with 3 subjects/cohort administering a bolus injection at escalating dose levels from 4 to 40 mg. One (1) planned multiple dose (MD), randomized, placebo-controlled expansion cohort with 9 NAFLD/NASH subjects will be enrolled for a 7-day dosing regimen at a dose level to be determined from the SAD portion of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Male and female subjects between the ages of 18 and 70 years, inclusive, at Screening. 2. Suspected or confirmed diagnosis of noncirrhotic NAFLD/NASH without advanced hepatic fibrosis by one of the following: 1. Histologically with liver biopsy within 2 years prior to Screening (documentation with pathology report); or 2. Radiologically with ≥5% steatosis measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), or controlled attenuation parameter (CAP) \>238 dB/m via FibroScan assessment, or presence of hepatic steatosis on abdominal ultrasound ; or 3. Clinically with a diagnosis of Metabolic Syndrome (MetS) reflecting the presence of at least 3 of 5 factors/criteria (ie, abdominal obesity, elevated triglycerides, reduced HDL-C, elevated blood pressure, and/or elevated fasting glucose \[IFG or type 2 diabetes mellitus\]) as defined by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) \[Grundy 2005\]; and fatty liver on imaging within 1 year prior to Screening. Key
Exclusion criteria
1. History or presence of cirrhosis as assessed by Investigator following review of diagnostic measures (clinical, imaging, histopathology, or laboratory). 2. Clinical evidence of hepatic decompensation (laboratory or clinical abnormalities- ascites, variceal bleeding, etc.). 3. History or presence of other concomitant liver disease (eg, hepatitis B & C, alcoholic liver disease, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin (A1AT) deficiency, bile duct obstruction, liver primary or metastatic cancer, drug-induced liver disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | 30 Days | Number of participants with treatment-emergent with adverse events (incidence and severity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the OA-235i Pharmacokinetics (PK) by AUC | 8 Days | OA-235i PK by area under the plasma concentration versus time curve (AUC) |
| To characterize the OA-235i Pharmacokinetics (PK) by Cmax | 8 Days | OA-235i PK by peak plasma concentration (Cmax) |
| To characterize the OA-235i Pharmacokinetics (PK) by t1/2 | 8 Days | OA-235i PK by the terminal elimination half-life (t1/2) |
| To characterize the OA-235i Pharmacokinetics (PK) by Tmax | 8 Days | OA-235i PK by time to peak plasma concentration (Tmax) |
Countries
United States
Outcome results
None listed