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

NCT05680233 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: OAS-235i-1015R44DK101240
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver

Outcome Measures

Primary Outcomes (1)

• Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Number of participants with treatment-emergent with adverse events (incidence and severity)

  30 Days

Secondary Outcomes (4)

• To characterize the OA-235i Pharmacokinetics (PK) by Cmax

  8 Days

• To characterize the OA-235i Pharmacokinetics (PK) by t1/2

  8 Days

• To characterize the OA-235i Pharmacokinetics (PK) by Tmax

  8 Days

• To characterize the OA-235i Pharmacokinetics (PK) by AUC

  8 Days

Study Arms (1)

OA-235i (4-40 mg)

EXPERIMENTAL

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.

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

Interventions

OA-235i (4 mg) DRUG

3 participants will receive 4 mg as a single subcutaneous dose

Also known as: PAR2 inhibitor

OA-235i (4-40 mg)

OA-235i (8 mg) DRUG

3 participants will receive 8 mg as a single subcutaneous dose

Also known as: PAR2 inhibitor

OA-235i (4-40 mg)

OA-235i (16 mg) DRUG

3 participants will receive 16 mg as a single subcutaneous dose

Also known as: PAR2 inhibitor

OA-235i (4-40 mg)

OA-235i (30 mg) DRUG

3 participants will receive 30 mg as a single subcutaneous dose

Also known as: PAR2 inhibitor

OA-235i (4-40 mg)

OA-235i (40 mg) DRUG

3 participants will receive 40 mg as a single subcutaneous dose

Also known as: PAR2 inhibitor

OA-235i (4-40 mg)

OA-235i or placebo DRUG

9 participants will receive a daily subcutaneous dose of OA-235i or placebo for 7 consecutive days

Also known as: PAR2 inhibitor, placebo

OA-235i (4-40 mg)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects between the ages of 18 and 70 years, inclusive, at Screening.
• 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) \>238 dB/m via FibroScan assessment, or presence of hepatic steatosis on abdominal ultrasound ; 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oasis Pharmaceuticals, LLC: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Mayo Clinic: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Athan Kuliopulos, MD, PhD

  Oasis Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 11, 2023
• Study Start: March 6, 2023
• Primary Completion: July 2, 2024
• Study Completion: July 2, 2024
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (1)