A Clinical Trial to Evaluate Safety of Gusacitinib in Patients With Systemic Lupus Erythematosus (SLE) or Lupus

Exclusion Criteria

• •An individual who meets any of the following criteria will be excluded from participation in this study:
• •Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study.
• •Subject has a history of cancer or lymphoproliferative disease within 5 years prior to Day 1. Note: Subjects with successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix are not to be excluded.
• •Subject has any clinically significant medical condition or physical / laboratory / ECG / vital signs abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.
• •Subject has 12-lead ECG abnormalities considered by the investigator to be clinically
• •significant or a QTcF \>= 450 milliseconds, regardless of clinical significance, at screening. Abnormal ECG may be confirmed with one repeated assessment. For subjects with a QTcF \>= 450 msec on initial ECG, the mean of the two QTcF values will determine eligibility.
• •Subject has congestive heart failure class III or IV as per the New York Heart Association (NYHA) classification.
• •Subject has a history of untreated recurrent venous thromboembolic event (VTE) (\>= 2 episodes in the past).
• •Subject has experienced any of the following within the last 6 months prior to Day 1: VTE, myocardial infarction, angioplasty, or cardiac stent placement, unstable ischemic heart disease, or stroke.
• •Subject had other major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study.
• •Subject has positive results for hepatitis B surface antigens (HBsAg), antibodies to hepatitis B core antigens (anti-HBc), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or BK viremia at the screening visit.
• •Subject has a known active tuberculosis (TB) or a positive TB infection test. Subject will be evaluated for latent TB infection with a purified protein derivative (PPD) test or a QuantiFERON-TB Gold test. Subjects who demonstrate evidence of latent TB infection (either PPD \>= 5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of Bacillus Calmette-Gu(SqrRoot)(Copyright)rin vaccination status) will only be allowed to participate in the study if there is documented evidence of a completed adequate treatment course for latent TB (with negative chest x-ray findings for active TB).
• •Subject has a known history of diverticulitis.
• •Subject has received any marketed or investigational biologic agent (such as rituximab, belimumab, anifrolumab etc.) within 12 months or 5 half-lives (whichever is longer) prior to Day 1.
• •Subject has received a live attenuated vaccine within 4 weeks prior to Day 1 or plans to receive a live attenuated vaccine during the study and up to 4 weeks or 5 half-lives (of the study product), whichever is longer, after the last study product administration.
• •Subject has used systemic (Intravenous) antibiotics within 2 weeks prior to Day 1.
• •Treatment with cyclophosphamide within the 6 months prior to screening.
• •A history of drug or alcohol abuse within the 6 months prior to screening.
• •Blood pressure not adequately controlled on the current medications.
• •History of chronic liver disease (moderate and severe hepatic impairment (Child-Pugh B and C) or elevated LFTs:
• •ALT or AST \>= 2x upper limit of normal at screening
• •serum unconjugated bilirubin \> 2mg/dL at screening
• •Dialysis or serum creatinine \>2 mg/dL.
• •Protein to creatinine ratio of more than 1000 mg/mg or 24 hours urine protein of more than 1000 mg.
• •Active urinary sediment (WBC casts, RBC casts or mixed cellular casts 1+ or more / mcL).
• •Hypercholesterolemia: Values after an 8-12 hour fasting blood specimen: total cholesterol \>250 mg/dL or LDL \>180 mg/dl or hypertriglyceridemia (triglyceride \>300 mg/dL) at screening visit.
• •Subjects with active renal or central nervous system involvement due to SLE or a BILAG A in any organ system.
• •WBC \<2500/ L or ANC \<1,000/ L, Hgb \<9.0 g/dL or platelets \<70,000/ L or absolute lymphocyte count \< 500/ L at screening and present on repeat testing up to 4 weeks apart
• •Current treatment with potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole) or receiving one or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) that would increase serum availability of Gusacitinib. Past treatment with the above mentioned agent is allowed if it was more than a week prior to the administration of the first dose of study medication.
• •Current treatment with strong and moderate inhibitors of CYPs 3A4, 2C8, 2D6, and inhibitors of BCRP and MDR1. Past treatment with the above mentioned agent is allowed if it was more than a week prior to the administration of the first dose of study medication.