A Study of IDN-6556 in Cirrhotic Subjects With Portal Hypertension
Condition: Liver Cirrhosis; Hepatic Cirrhosis; Portal Hypertension
MeSH terms: Liver Cirrhosis; Hypertension, Portal; Hypertension; Fibrosis
Intervention: IDN-6556
Intervention description: 25 mg BID
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Liver Cirrhosis; Hepatic Cirrhosis; Portal Hypertension

Summary:

      This is an open-label pilot study to evaluate the safety, tolerability, and efficacy of
      IDN-6556 in treating portal hypertension in subjects with liver cirrhosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects of minimum adult legal age (according to local laws for
             signing the informed consent document), able to provide written informed consent, and
             able to understand and willing to comply with the requirements of the study

          -  Clinical, radiological, or biochemical evidence of liver cirrhosis

          -  Evidence of portal hypertension as evidenced by any of the following:

               1. Splenomegaly, on imaging and/or clinical evaluation, with platelet count of
                  <120,000 at study entry, or

               2. Presence of small sized varices on screening endoscopy and/or collateral
                  circulation on imaging, or

               3. Presence of medium/large varices that have never bled and have been obliterated
                  with endoscopic ligation

          -  Portal hypertension defined as a hepatic venous pressure gradient (HVPG) >5 mmHg at
             Screening

          -  Willingness to utilize two reliable forms of contraception (for both males and females
             of childbearing potential) from Screening to one month after the last dose of study
             drug.

        Exclusion Criteria:

          -  Decompensated cirrhosis as defined by the presence of overt ascites (requiring
             diuretics), overt encephalopathy (requiring specific therapy), or history of variceal
             hemorrhage.

          -  Known infection with HIV

          -  Hepatic failure defined as total bilirubin ≥12 mg/dL

          -  Other non-liver organ failure, including:

               1. Renal failure defined as creatinine ≥ 2.0 mg/dL

               2. Cerebral failure defined as hepatic encephalopathy grade III or IV

               3. Coagulation failure defined as INR ≥ 2.5 or platelets ≤ 20x109/L

               4. Hemodynamic requirement for inotropic support

          -  Child-Pugh score of 10-15 (Child-Pugh C classification)

          -  Use of vasoactive drugs (at or within 3 months of Screening) that may impair hepatic
             blood flow; examples include but are not limited to:

               1. β-blockers, including carvedilol

               2. Nitrates

               3. Vasopressin (or analogues)

               4. Phosphodiesterase inhibitors (prescribed daily for pulmonary hypertension; p.r.n.
                  use for erectile dysfunction is permitted)

          -  Change in dose or regimen within 3 months of Screening of:

               1. Fibrates or statins

               2. Angiotensin II receptor antagonist or angiotensin converting enzyme (ACE)
                  inhibitor

          -  Use of the following drugs within 2 months of Screening:

               1. Systemic corticosteroids

               2. Pentoxifylline

               3. Known or suspected use of illicit drugs or drugs of abuse (allowed if medically
                  prescribed or indicated)

          -  Concomitant pancreatitis

          -  Evidence of portal vein thrombosis on Doppler ultrasound of the portal vasculature

          -  Active inflammatory bowel disease

          -  Diagnosed or suspected systemic lupus erythematosus (SLE) and/or rheumatoid arthritis
             (RA)

          -  Autoimmune hepatitis

          -  Hepatitis C Virus (HCV) infected subjects receiving or planning on receiving
             anti-viral therapy during the course of the study

          -  Hepatitis B Virus (HBV) infected subjects who have been on stable anti-HBV therapy for
             less than 3 months

          -  Hepatocellular carcinoma (HCC) at entry into the study

          -  Active non-liver malignancies other than curatively treated skin cancer (basal cell or
             squamous cell carcinomas)

          -  History or presence of clinically concerning cardiac arrhythmias, or prolongation of
             screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec)

          -  Significant systemic or major illness other than liver disease, including coronary
             artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious
             psychiatric disease, that, in the opinion of the Investigator would preclude the
             subject from participating in and completing the study

          -  Any subject that has received any investigational drug or device within 30 days of
             dosing or who is scheduled to receive another investigational drug or device in the
             course of the study

          -  If female, known pregnancy, or has a positive urine or serum pregnancy test, or
             lactating/breastfeeding.