Clinical Trials

Inclusion Criteria:

• Male subjects or female subjects between the ages of 18 and 70 years, inclusive, at Screening.
• Body mass index (BMI) ≥ 25 and <40 kg/m2; and a total body weight ≥50 and ≤150 kg at Screening and Day 1 Pre-dose.
• Suspected or confirmed diagnosis of noncirrhotic NAFLD/NASH with no fibrosis to moderate fibrosis (stages F0-F2) by one of the following:
  • Histologically with liver biopsy within 2 years prior to Screening (documentation with pathology report) [Chalasani 2018]; or
  • Radiologically with ≥5% steatosis measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), or controlled attenuation parameter (CAP™)and 288 dB/m via FibroScan® assessment, or presence of hepatic steatosis on abdominal ultrasound; and an increase in serum alanine aminotransferase (ALT) > 30 U/L within 1 year prior to Screening; 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 seronegative hepatitis B and C; and fatty liver on imaging within 1 year prior to Screening.
• Subjects who are willing and able to comply with all scheduled visits, clinical research unit (CRU) confinement, dosing plan, laboratory tests, and other study procedures and restrictions detailed in this protocol and listed in the informed consent form/document (ICF).
• Evidence of a personally signed and dated ICF, approved by the IRB, indicating that the subject has been informed of all pertinent aspects of the study, understands, and voluntarily agrees to participate in the study, and authorizes the use of protected health information (PHI) in accordance with national and local subject privacy regulations (ie, HIPAA) prior to the initiation of any study-specific procedure.

Exclusion Criteria:

• History or presence of cirrhosis by any diagnostic measure (clinical, imaging, histopathology, or laboratory).
• History or presence of other concomitant liver disease as assessed by the Investigator or determined by laboratory findings including, but not limited to the entities listed below:
  • Hepatitis B virus (HBV), defined by presence of hepatitis B surface antigen (HepBsAg) and hepatitis B core antibody (HepBcAb);
  • Hepatitis C virus (HCV), defined by presence of hepatitis C antibody (HCVAb), and HCV RNA (when reflexed based on a positive result for HCVAb);
  • Human Immunodeficiency Virus (HIV) infection, defined as presence of HIV antibody;
  • Alcoholic liver disease;
  • Autoimmune liver disease as defined by compatible liver histology;
  • Primary biliary cholangitis (PBC) as defined by the presence of at least 2 of the following:
    • Biochemical evidence of cholestasis based mainly on alkaline phosphatase (ALP) elevation;
    • Presence of anti-mitochondrial antibody (AMA);
    • Histologic evidence of nonsuppurative destructive cholangitis and destruction of interlobular bile ducts.
  • Primary sclerosing cholangitis (PSC);
  • Hemochromatosis or iron overload, defined by presence of 3+ or 4+ stainable iron on liver biopsy;
  • Wilson’s disease, defined by ceruloplasminand < LLN and compatible liver histology;
  • Alpha-1 antitrypsin (A1AT) deficiency, defined by A1AT level < LLN and compatible liver histology;
  • Bile duct obstruction;
  • Suspected or known primary liver cancer (eg, hepatocellular carcinoma) or metastatic cancer involving liver;
  • Prior known drug-induced liver injury (DILI), defined on the basis of typical exposure and history;
  • Any other type of liver disease other than NASH.
• Clinical evidence of hepatic decompensation as defined by the presence of any of the following abnormalities:
  • Serum albumin 1.3 < 3/2 gdL;
  • INR > 1.3;
  • Direct bilirubin >1.3 mg/dL;
  • History of esophageal varices, ascites, or hepatic encephalopathy.
• History of pancreatic disease including acute/chronic pancreatitis, pancreas divisum, annular pancreas or prior history of pancreatic surgery.
• Evidence of portal hypertension (eg, low platelet counts, esophageal varices, ascites, history of hepatic encephalopathy, splenomegaly).
• Weight loss ≥ 5% within 6 months prior to Screening.
• Prior or planned (during the study period) bariatric surgery or any other gastrointestinal surgery relative to weight loss (eg, Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, sleeve gastrectomy, duodenal switch with biliopancreatic diversion).
• Uncontrolled diabetes, defined as HbA1c of ≥ 9.5% within 60 days prior to Screening.
• History or presence of a compromised immune system including inherited deficiencies of the immune system; immunosuppressing/immunomodulating drugs including, but not limited to, steroids (corticosteroid, anabolic), antimetabolites, immunoglobulins or cytokine-based therapies within 6 months prior to Day 1 or is expected to receive these agents during study participation; or other conditions causing leukopenia or neutropenia.
• History of malignancy and/or lymphoproliferative disease (suspected disease and/or systemic treatment) or systemic treatment for malignancy (eg, chemotherapy, biologics, vaccines, hormonal treatment, or non-localized radiation therapy) within 5 years prior to Screening with the following exceptions: non-metastatic squamous or basal cell carcinoma of the skin and in-situ cancers (bladder, colon, cervix, or breast) curatively treated at least 1 year prior to Screening visit with no current evidence of disease.
• History of severe allergy or hypersensitivity (eg, anaphylaxis, hepatotoxicity) to a drug or diagnostic imaging agent which required urgent medical treatment (including any component of the IP or other products in the same class), or a history of other allergy that, in the opinion of the Investigator or Sponsor, contraindicates their participation.
• Evidence of poor peripheral venous access that limits phlebotomy, or the inability to have blood drawn.
• Inability to tolerate subcutaneous injection medication(s).
• Clinically significant or unstable cardiovascular disease including, but not limited to the following: unstable angina, myocardial infarction, stroke, or transient ischemic attack within the past 6 months of Screening; ventricular arrhythmia (eg, ventricular tachycardia, ventricular fibrillation or torsades de points) or a family history of long QT syndrome or unexplained death in an otherwise healthy individual between ages of 1 and 30 years; peripheral vascular disease; or other heart conditions (eg, dilated cardiomyopathy with left ventricular ejection fraction < 40% implanted defibrillator or pacemaker, congestive heart failure with New York Association [NYHA] class III or IV, pericarditis, significant pericardial effusion, myocarditis); or other condition that requires the routine use of supplemental oxygen.
• Syncope, palpitations, or unexplained dizziness.
• Previous episodes of seizures or convulsion (lifetime), including absence seizure and febrile convulsion.
• Chronic respiratory disease including chronic obstructive pulmonary disease (COPD), emphysema, cystic fibrosis, pulmonary hypertension, or other chronic condition that requires the routine use of supplemental oxygen.
• Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test at Screening.
• Subjects with a significant Coronavirus disease 2019 (COVID-19) illness within 6 months of enrollment:
  • Diagnosis of COVID-19 pneumonia based on radiological assessment;
  • Diagnosis of COVID-19 with significant findings from pulmonary imaging tests;
  • Diagnosis of COVID-19 requiring hospitalization and/or oxygen supplementation.
• Active infection or use of antibiotic(s) within 28 days prior to Day 1.
• History of any significant bleeding event defined as CTCAE ≥Grade 3 (includes receipt of hematopoietic growth factors, blood, or blood product transfusion) within 3 months prior to Screening; or personal/family history of bleeding disorder (eg, hemophilia, factor deficiencies, disseminated intravascular coagulation).
• Major trauma or surgery including but not limited to operations involving a major organ (eg, the cranium, chest, abdomen, or pelvic cavity) OR requiring a lengthy recovery period (eg, arthroplasty) within 4 weeks prior to Screening; or planned surgery during the study. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 2 weeks before Day 1.
• Subjects currently experiencing any clinically significant or unstable medical condition that might limit their ability to complete the study, to comply with the requirements of the protocol, or interfere with the interpretation of study results which, in the judgment of the Investigator, would make the subject inappropriate for entry into this study, including: dermatologic disease, hematological disease, pulmonary disease, hepatic disease, gastrointestinal disease, genitourinary disease, endocrine disease, neurological disease and psychiatric disease.
• History of substance abuse (eg, alcohol, drugs), within 1 year prior to Screening.
• Current or history of significant alcohol consumption exceeding 14 drinks/week for female subjects or 21 drinks/week for male subjects (1 drink = 5 ounces [150 mL] of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within the previous 6 months from Screening; or inability to reliably quantify alcohol intake based on Investigator’s judgment.
• Positive alcohol breath test result or positive urine drug screen at Screening or Day 1 Predose;
  • [NOTE: Subjects who have been medically prescribed benzodiazepines and report the use of these drugs to the Investigator at Screening may be allowed to participate.]
• Subjects with any of the following abnormalities in clinical laboratory tests at Screening or Day 1 Pre-dose, as assessed by the study-specific clinical laboratory and confirmed by a single repeat test, if deemed necessary:
  • Serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) > 5 × Upper Limit of Normal (ULN);
  • Direct Bilirubin > ULN;
    • [NOTE: Subjects with a history of Gilbert syndrome would be eligible for this study provided direct bilirubin level is ≤ULN plus ALT met criteria plus alkaline phosphatase, hemoglobin, and reticulocyte count are ≤ULN.];
  • Platelet count < 150,000/mm^3;
  • International Normalized Ratio (INR) > ULN;
  • Fasting triglycerides ≥ 400 mg/dl 28.
• The presence of abnormal laboratory values (other than those explicitly mentioned in Section 5.2) at Screening or Day 1 Pre-dose considered to be clinically significant by the Investigator (ie, suggestive of underlying disease or increased risk of IP administration). A single repeat measurement/test may be performed to confirm clinical laboratory test(s) abnormalities.
• Supine systolic blood pressure (BP) ≥140 mm Hg and/or diastolic BP ≥ 90 mm Hg after ≥5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the BP may be repeated 2 more times and the average of the 3 BP values will be used to determine the subject’s eligibility.
• Supine systolic BP ≤ 85 mm Hg and/or diastolic BP ≤ 55 mm Hg after ≥ 5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the BP may be repeated 2 more times and the average of the 3 BP values will be used to determine the subject’s eligibility.
• Supine heart rate (HR)/pulse outside the range of 50-100 bpm (not on ECGs) after ≥ 5 minutes of rest at Screening or Day 1 Pre-dose. If needed, the HR may be repeated 2 more times and the average of the 3 HR values will be used to determine the subject’s eligibility.
• Supine 12-lead ECG demonstrating Fridericia method-corrected QT (QTcF) interval >450 msec or a QRS interval >120 msec after ≥10 minutes of rest at Screening or Day 1 Pre-dose. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTcF or QRS values should be used to determine the participant’s eligibility.
• Subjects with an estimated glomerular filtration rate (eGFRcr) < 90 mL/min/1.73m2 as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI, 2021) equation, based on serum creatinine and age at Screening or Day 1 Pre-dose.
• Blood donation of approximately 1 pint (500 mL) or more within 56 days prior to Screening, or donation of blood products (eg, plasma, platelets) within 2 weeks prior to Screening; or
  subject is unwilling to forego blood product donation beginning at Screening and for the duration of the study.
• Pregnant female subjects; breastfeeding female subjects; female subjects of childbearing potential with a positive serum pregnancy result at Screening or positive urine pregnancy result on Day 1 Pre-dose; female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol from the date of signing of informed consent until at least 30 days after the final dose of IP (Section 5.4); female subjects of childbearing potential who are unwilling to refrain from ova donation from start of IP dosing (CRU admission) until at least 30 days after final dose of IP.
• Male subjects who are unwilling or unable to an acceptable method of contraception from the date of Day 1 Pre-dose (baseline) until at least 30 days after the final dose of IP (Section 5.4); male subjects who are unwilling to refrain from sperm donation from the start of IP dosing (CRU admission) until at least 30 days after the final dose of IP.
• Unwilling or unable to comply with the protocol restrictions and lifestyle/activity requirements (Section 5.3) of this protocol.
• Vaccinated or exposed to a live or attenuated vaccine within 2 weeks prior to Screening or anticipated vaccination during the study.
• Participation in another clinical trial (investigational drug, vaccine, medical device, or procedure) within 30 days or 5 half-lives (drug) prior to Day 1 (whichever is longer); planned participation of clinical trial during the study; participation in ≥2 clinical trials within 6 months prior to Screening. Non-interventional follow-up/surveillance for an earlier study will be allowed.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
• Subjects with known prior participation in a trial involving OA-235i (ie, received at least 1 dose of IP).
• Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Oasis employees, including their family members, directly involved in the conduct of the study.
• Use of the following medications (prescription or over-the-counter [OTC] drugs) or therapies (herbal, homeopathic preparations) within 4 weeks or 5 half-lives (whichever is longer) prior to Day 1 or intention/anticipated use during the study:
  • [NOTE: Subjects who received any of the following medications are eligible if the noted minimum washout criteria are observed and they are not used as concomitant treatments during the study.]
    • Systemic non-steroidal anti-inflammatory drugs (NSAIDs) (chronic use [ie, > 4 days/week]);
    • Coumadin-type anticoagulants (warfarin);
    • Antiarrhythmics, except for beta blockers or calcium channel blockers if used for the management of conditions other than arrhythmias;
    • Anticonvulsants (eg, topiramate);
    • Ezetimibe (Zetia);
    • Fibric acid derivatives (fibrates);
    • Omega-3 fatty acids (fish oil) ;
    • Systemic corticosteroids (inhaled and topical corticosteroids are allowed) (bronchodilator inhalers are allowed);
    • Prescription opioids (eg, hydrocodone [Vicodin®], oxycodone [OxyContin®, Percocet®], oxymorphone [Opana®], morphine [Kadian®, Avinza®], codeine, fentanyl);
    • Medical-grade marijuana, regardless of medical indication;
    • Herbal, nutraceutical, or natural supplement (daily multi-vitamin is allowed)
    • Medications which have been associated with causing/worsening NAFLD/NASH: amiodarone, methotrexate, tetracyclines, tamoxifen, griseofulvin, estrogens at doses greater than those used for hormone replacement (> 2 mg/day), anabolic steroids, valproic acid, nucleoside analogues (except acyclovir), bile acid sequestrants (eg, cholestyramine, colestipol), total parenteral nutrition, and other known hepatotoxins;
    • Medications that may cause pancreatitis: glucagon-like peptide-1 receptor agonists (GLP1 Ras): dulaglutide (Trulicity), exenatide (Byetta), exenatide extended-release (Bydureon), liraglutide (Victoza), lixisenatide (Adlyxin), oral semaglutide (Rybelsus), semaglutide (Ozempic);
    • Certain medications to treat NAFLD/NASH and coexisting conditions such as diabetes, hyperlipidemia, and hypertension will be allowed; however, subjects must be on a stable dose for the noted period of time prior to Day 1:
      • Medications to treat NAFLD/NASH (eg, vitamin E, betaine, s-adenosyl-l-methionine, ursodeoxycholic acid, probiotics, and thiazolidinediones [TZDs]) – subjects must be on a stable dose for at least 6 months prior to Day 1 and still carry a current diagnosis;
      • Anti-diabetic medications (eg, biguanides [metformin], insulin) – subjects must be on a stable dose for at least 12 weeks prior to Day 1; sliding scale of insulin is allowed if the subject's HbA1c remains <9.5%. Subject’s taking other sc drugs (eg, insulin) must be instructed to avoid injections within 20 cm of any given IP injection site for the duration of the trial;
      • HMG-CoA reductase inhibitors (ie, statins) – subjects without a history of cardiovascular disease (CVD) (ie, symptomatic coronary artery disease or ischemic stroke) who are taking a statin for primary prevention are eligible for the trial, but must be discontinued from concomitant statin therapy beginning at least 1 week prior to Day 1 (wash-out) and continuing through 1 week following the final study drug dose; these subjects must also have been on a stable statin dose for at least 8 weeks prior to the wash-out. Note, subjects who have developed CVD and are taking a statin for secondary prevention are ineligible for the trial;
      • Other lipid modifying medications (eg, nicotinic acid/niacin) – subjects must be on a stable dose for at least 8 weeks prior to Day 1.
      • Antihypertensive agents – subjects must be on a stable dose for at least 8 weeks prior to Day 1.
  • Any Investigator questions or concerns regarding the use of treatments, including medications (ie, prescription and OTC drugs) and non-medication therapies (eg, vitamins, nutritional supplements, immunizations) should be discussed with the Oasis Medical Officer/Monitor prior to the subject’s study enrollment and IP administration.

  • Eligibility last updated 7/25/22. Questions regarding updates should be directed to the study team contact.