Safety Study of OA-235i in Subjects With Nonalcoholic Steatohepatitis

Oasis Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Nonalcoholic Fatty Liver; Nonalcoholic Steatohepatitis

Treatments: Drug: OA-235i or placebo; Drug: OA-235i (4 mg); Drug: OA-235i (16 mg); Drug: OA-235i (30 mg); Drug: OA-235i (8 mg); Drug: OA-235i (40 mg)

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05680233

OAS-235i-101

5R44DK101240 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 1 patient group

OA-235i (4-40 mg)

Experimental group

Description:

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) or placebo 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.

Treatment:

Drug: OA-235i (40 mg)

Drug: OA-235i (8 mg)

Drug: OA-235i (30 mg)

Drug: OA-235i (16 mg)

Drug: OA-235i (4 mg)

Drug: OA-235i or placebo