Phase 2a to Evaluate PL-8177 in Subjects with Active Ulcerative Colitis (UC)

Exclusion Criteria

• •Subjects will be excluded from the study if they meet any of the following criteria at the Screening visit unless otherwise stated:
• •Any condition, physical finding, laboratory or ECG abnormality, which, in the opinion of the Investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject.
• •Has fulminant colitis, toxic megacolon, microscopic colitis, history of colitis-associated colonic dysplasia, active peptic ulcer disease, cervical dysplasia, or primary sclerosing cholangitis.
• •History of Crohn's disease or indeterminate colitis, or the presence or history of a fistula consistent with Crohn's disease.
• •Presence of ileostomy or colostomy, or history of prior colon resection.
• •Presence of adenomatous colonic polyps that have not been removed.
• •Stools positive for C. difficile, enteric pathogens (Salmonella, Shigella, Campylobacter), or ova and parasites within 28 days of screening. Screen failures due to positive C. difficile or other enteric infection can be re-screened after appropriate treatment.
• •History of mitochondrial disorder.
• •History of primary or secondary immunodeficiency.
• •History of cancer within the 5 years prior to screening including solid tumors and hematological malignancies (exception: no approval needed for basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no re-occurrence for at least 1 year prior to screening).
• •History of one or more clinically relevant neurologic, psychologic, ophthalmologic, pulmonary, cardiovascular, gastrointestinal (other than the UC), hepatic, renal, endocrine, or other major systemic disease of moderate (or worse) severity, making implementation of the protocol or interpretation of the study difficult. Examples of (but not limited to) conditions to be excluded, are the following:
• •Uncontrolled hypertension, with systolic blood pressure (SBP) ≥160 mmHg, diastolic blood pressure (DBP) ≥90 mmHg.
• •Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL\>200 mg/dl or triglycerides \>500 mg/dL).
• •Known uncontrolled hyperthyroidism or hypothyroidism.
• •Impaired hepatic function (Aspartate aminotransferase \[AST\] or Alanine aminotransferase \[ALT\] values \>2.0 times the upper limit of the reference range and/or serum bilirubin \>1.5 times the upper limit of the reference range at the screening visit).
• •Cardiac or pulmonary disease, such as unstable angina or myocardial infarction within the past 12 months, congestive heart failure (CHF) Grade 2, 3, or 4 according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, or chronic pulmonary disease requiring oxygen, venous thrombosis.
• •Stroke or transient ischemic attack (TIA) in the 12 months before screening.
• •Major depressive illness in the last 3 years; any history of severe psychiatric illness (eg, schizophrenia).
• •Multiple sclerosis or any other demyelinating disease.
• •Any of the following laboratory abnormalities:
• •* Hemoglobin \<8.5 g/dl (international system units \[SI\]: \<85 g/L).
• •* Neutrophils \<1500/mm3 (SI: \< 1.5 x 109/L).
• •* White blood cell (WBC) count \<3,000/mm3 (SI: \< 3.0 x 109/L).
• •* Platelets \<80,000 mm3 (SI: 80 x 109/L).
• •* International normalized ratio (INR) \>1.5.
• •* Serum creatinine \>1.5 x the upper limit of normal.
• •Has a current bacterial, parasitic, fungal, viral, or mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks prior to the screening visit, and/or oral antibiotics within 2 weeks prior to screening visit and at any time during the screening period.
• •Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCVAb) at Screening (note: HCV subjects with undetectable viral load will be eligible).
• •Clinically significant findings on 12-lead ECG such as, but not limited to, 2nd or 3rd degree AV block, prolongation of QRS complex over 120 msec, or QTcF interval ≥450 msec for males and ≥470 msec for females.
• •Medications of exclusion:
• •Non-steroidal anti-inflammatory drugs (NSAIDs) daily.
• •Subjects on anti-coagulation therapy within 28 days prior to screening and through Day 56.
• •Note: (A daily dose of ASA 81mg, taken for cardio prophylaxis, is considered acceptable to be continued during the study.)
• •Topical (i.e., enema or suppository) mesalamine or steroid within 14 days prior to screening endoscopy.
• •Azathioprine, 6-mercaptopurine, or methotrexate within the 28 days prior to screening.
• •Any prior use of mycohphenolic acid, tacrolimus, sirolimus, cyclosporine, thalidomide
• •Any prior use of biologics: rituximab, efalizumab, anti-integrines (natalizumab, vedolizumab, etrolizumab), TNF antagonists (infliximab, , golimumab, certolizumab pegol), anti-IL-12/23 (ustekinumab, guselkumab, risankizumab, or mirikizumab) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter).
• •Any prior use of small molecules: JAK inhibitors (tofacitinib, baricitinib, upadacitinib, or other) or S1P receptor modulator (fingolimod, ozanimod, etrasimod) ≤ 3 months prior to first dosing or ≤ 5 elimination half-lives prior to first dosing (whichever is shorter).
• •Use of PPI (proton pump inhibitor) during the study (Should be discontinued 72 hours prior to Day 1).
• •Use of prescription medications started or with a dose adjustment within 4 weeks prior to study screening, or over-the-counter medications or supplements started or with a dose adjustment within 2 weeks prior to study screening. Medications under Inclusion Criterion #5 are not included. Short-term administration of drugs for acute conditions are acceptable.
• •Anti-diarrheal medications are not allowed within 48 hours of screening and throughout the study.
• •Participated in another clinical trial of an investigational drug (or medical device) within 30 days prior to screening or is currently participating in another trial of an investigational drug (or medical device).
• •Subjects with planned hospitalization or surgery during the study.
• •Subject has known sensitivity to any of the products or components to be administered during dosing.
• •Has previously received PL8177.
• •History of alcohol or drug abuse and/or positive drug test at screening (with exception of marijuana if legal within the state and no drug abuse is noted in the PI's assessment)
• •Positive TB or COVID 19 test. Note: Patients with positive TB results who had active or latent TB in the two years preceding the screening visit and who were treated for TB can participate in study