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

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05680233
• Other study ID #: OAS-235i-101
• Secondary ID: 5R44DK101240
• Status: Recruiting
• Phase: Phase 1
• Start date: January 23, 2023
• Est. completion date: April 2024

Study information

• Verified date: September 2023
• Source: Oasis Pharmaceuticals, LLC
• Contact: Manal Abdelmalek, MD
• Phone: 507-284-2511
• Email: Abdelmalek.manal[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 23
• Est. completion date: April 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver
• Nonalcoholic Steatohepatitis

Intervention

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

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Oasis Pharmaceuticals, LLC	Mayo Clinic, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

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