Clinical trial NCT05680233: Safety Study of OA-235i in Subjects With Nonalcoholic Steatohepatitis
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Nonalcoholic Steatohepatitis
Nonalcoholic Fatty Liver
Lead sponsor: Oasis Pharmaceuticals, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Mayo Clinic
First posted: 2023-01-11
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: 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) 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 30 Days
Secondary outcomes:
measure: To characterize the OA-235i Pharmacokinetics (PK) by Cmax
timeFrame: 8 Days
measure: To characterize the OA-235i Pharmacokinetics (PK) by t1/2
timeFrame: 8 Days
measure: To characterize the OA-235i Pharmacokinetics (PK) by Tmax
timeFrame: 8 Days
measure: To characterize the OA-235i Pharmacokinetics (PK) by AUC
timeFrame: 8 Days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Oasis Pharmaceuticals, LLC
name: Athan Kuliopulos, MD, PhD
role: STUDY_DIRECTOR
References: