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

A Phase 1a/1b Single Ascending and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of OA-235i, a PAR2 Inhibitor, in Adults With Nonalcoholic Steatohepatitis

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.

Study Overview

• Status: Recruiting
• Conditions: Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver
• Intervention / Treatment: Drug: OA-235i (4 mg); Drug: OA-235i (8 mg); Drug: OA-235i Dose 3; Drug: OA-235i Escalating Dose 4; Drug: OA-235i Escalating Dose 5; Drug: OA-235i Multiple Dose

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.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Manal Abdelmalek, MD; Phone Number: 507-284-2511; Email: Abdelmalek.manal@mayo.edu
• Study Contact Backup: Name: Christopher Kigongo; Phone Number: 507-226-1998; Email: Kigongo.Christopher@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Manal Abdelmalek, MD; Phone Number: 507-284-2511; Email: Abdelmalek.manal@mayo.edu
      • Contact: Christopher Kigongo; Phone Number: 507-226-1998; Email: Kigongo.Christopher@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Male and female subjects between the ages of 18 and 70 years, inclusive, at Screening.
2. 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.

3. 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) >288 dB/m via FibroScan assessment, or presence of hepatic steatosis on abdominal ultrasound within 1 year prior to Screening; 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: OA-235i (4-40 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.

Drug: OA-235i (4 mg); 3 participants will receive 4 mg as a single subcutaneous dose; Other Names: PAR2 inhibitor; Drug: OA-235i (8 mg); 3 participants will receive 8 mg as a single subcutaneous dose; Other Names: PAR2 inhibitor; Drug: OA-235i Dose 3; 3 participants will receive a single escalating subcutaneous dose; Other Names: PAR2 inhibitor; Drug: OA-235i Escalating Dose 4; 3 participants will receive a single escalating subcutaneous dose; Other Names: PAR2 inhibitor; Drug: OA-235i Escalating Dose 5; 3 participants will receive a single escalating subcutaneous dose; Other Names: PAR2 inhibitor; Drug: OA-235i Multiple Dose; 8 participants will receive a daily subcutaneous dose for 7 consecutive days; Other Names: PAR2 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the OA-235i Pharmacokinetics (PK) by Cmax	OA-235i PK by peak plasma concentration (Cmax)	8 Days
To characterize the OA-235i Pharmacokinetics (PK) by t1/2	OA-235i PK by the terminal elimination half-life (t1/2)	8 Days
To characterize the OA-235i Pharmacokinetics (PK) by Tmax	OA-235i PK by time to peak plasma concentration (Tmax)	8 Days
To characterize the OA-235i Pharmacokinetics (PK) by AUC	OA-235i PK by area under the plasma concentration versus time curve (AUC)	8 Days

Collaborators and Investigators

• Sponsor: Oasis Pharmaceuticals, LLC
• Collaborators: Mayo Clinic; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Study Director: Athan Kuliopulos, MD, PhD, Oasis Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2023
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: January 3, 2023
• First Posted (Actual): January 11, 2023

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: OAS-235i-101; 5R44DK101240 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No