Safety Study of OA-235i in Subjects With Nonalcoholic Steatohepatitis
- Conditions
- Nonalcoholic SteatohepatitisNonalcoholic Fatty Liver
- Interventions
- Drug: OA-235i (4 mg)Drug: OA-235i (8 mg)Drug: OA-235i Dose 3Drug: OA-235i Escalating Dose 4Drug: OA-235i Escalating Dose 5Drug: OA-235i Multiple Dose
- Registration Number
- NCT05680233
- Lead Sponsor
- Oasis Pharmaceuticals, LLC
- Brief Summary
This study is a Phase 1, first-in-human single-dose escalation 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) expansion dose cohort with 8 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 23
-
Male and female subjects between the ages of 18 and 70 years, inclusive, at Screening.
-
Body mass index (BMI) of ≥25 and <40 kg/m2 with a total body weight 50-150 kg (inclusive) at Screening and Day 1 Pre-dose.
-
Suspected or confirmed diagnosis of noncirrhotic NAFLD/NASH without advanced hepatic fibrosis by one of the following:
- Histologically with liver biopsy within 2 years prior to Screening (documentation with pathology report); or
- Radiologically with ≥5% steatosis measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), or controlled attenuation parameter (CAP) >288 dB/m via FibroScan assessment, or presence of hepatic steatosis on abdominal ultrasound within 1 year prior to Screening; or
- 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
- History or presence of cirrhosis as assessed by Investigator following review of diagnostic measures (clinical, imaging, histopathology, or laboratory).
- Clinical evidence of hepatic decompensation (laboratory or clinical abnormalities- ascites, variceal bleeding, etc.).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description OA-235i (4-40 mg) OA-235i (8 mg) Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. OA-235i (4-40 mg) OA-235i Dose 3 Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. OA-235i (4-40 mg) OA-235i Escalating Dose 4 Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. OA-235i (4-40 mg) OA-235i Escalating Dose 5 Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. OA-235i (4-40 mg) OA-235i (4 mg) Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. OA-235i (4-40 mg) OA-235i Multiple Dose Single ascending dose (SAD): OA-235i (4-40 mg) administered subcutaneously (SC) once to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis. Multiple dose (MD): OA-235i (dose level to be determined from SAD) administered subcutaneously (SC) once daily for 7 days to adult subjects with suspected or confirmed diagnosis of noncirrhotic nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) without advanced hepatic fibrosis.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)
To characterize the OA-235i Pharmacokinetics (PK) by AUC 8 Days OA-235i PK by area under the plasma concentration versus time curve (AUC)
Trial Locations
- Locations (1)
Mayo Clinic
🇺🇸Rochester, Minnesota, United States