A Study to Evaluate Pegylated Interferon Lambda Monotherapy in Patients With Chronic Hepatitis Delta Virus Infection
Condition: Hepatitis D, Chronic
MeSH terms: Hepatitis A; Virus Diseases; Hepatitis D; Hepatitis D, Chronic; Hepatitis
Intervention: Peginterferon Lambda-1A
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      To evaluate safety and tolerability of lambda over a 48-week treatment period in HDV
      patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chronic HDV infection of at least 6 months' duration documented by a positive HDV
             antibody (Ab) test, detectable and quantifiable HDV RNA by qPCR at study entry

          -  Serum alanine aminotransferase (ALT) > upper limit of the normal range (ULN) and <10 ×
             ULN at screening

          -  Electrocardiogram (ECG) demonstrating no acute ischemia or clinically significant
             abnormality and a QT interval corrected for heart rate (QTcF) <450 ms for male
             patients and <460 ms for female patients

          -  Thyroid-stimulating hormone (TSH) and/or free T4 within 0.8 to 1.2 × ULN, or
             adequately controlled thyroid function as assessed by the investigator.

          -  Dilated retinal examination ≤1 year before screening

          -  Female patients of childbearing potential and male patients with partners of
             childbearing potential must agree to use adequate methods of contraception during the
             study and through 90 days after the last dose of study medication

        Exclusion Criteria:

        General Exclusions:

          -  Participation in a clinical trial with or use of any investigational agent within 30
             days before screening, or treatment with interferons (IFNs) or immunomodulators within
             12 months before screening

          -  Previous use of Lambda. Patients who previously participated in a clinical trial of
             Lambda but are confirmed to have received placebo or other non-Lambda IFNs are
             allowed.

          -  History or evidence of any intolerance or hypersensitivity to IFNs or other substances
             contained in the study medication.

          -  Female patients who are pregnant or breastfeeding. Male patients must confirm that
             their female sexual partners are not pregnant.

        Exclusions Based on Disease

          -  Current or previous history of decompensated liver disease (Child-Pugh Class B or C)

          -  Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)

          -  Past history or current evidence of decompensated liver disease, defined as any of the
             following at screening:

               1. Bilirubin level ≥ 2.5 mg/dL unless due to Gilbert's disease

               2. Serum albumin level <3.5 g/dL

               3. International normalized ratio (INR) ≥1.5

               4. Alpha fetoprotein ≥100 ng/mL

          -  Evidence of significant portal hypertension; current presence or history of variceal
             bleeding, ascites requiring diuretics or paracentesis, or hepatic encephalopathy

          -  Any of the following abnormal laboratory test results at screening:

               1. Platelet count <90,000 cells/mm^3

               2. White blood cell count <3,000 cells/mm^3

               3. Absolute neutrophil count <1,500 cells/mm^3

               4. Hemoglobin <11 g/dL for women and <12 g/dL for men

               5. Serum creatinine concentration ≥1.5× ULN

               6. Confirmed creatinine clearance (CrCl) < 50 mL/min by Cockcroft-Gault

          -  Evidence of another form of viral hepatitis or another form of liver disease

          -  History of hepatocellular carcinoma

          -  Patients with any of the following:

               1. Current eating disorder or alcohol abuse

               2. Excessive alcohol intake

               3. In the opinion of the investigator, an alcohol use pattern that will interfere
                  with study conduct

               4. Drug abuse within the previous 6 months before screening, with the exception of
                  cannabinoids and their derivatives

          -  Prior history or current evidence of any of the following:

               1. Immunologically mediated disease

               2. Retinal disorder or clinically relevant ophthalmic disorder

               3. Any malignancy within 5 years before screening

               4. Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease.

               5. Chronic pulmonary disease

               6. Pancreatitis

               7. Severe or uncontrolled psychiatric disorder

               8. Active seizure disorder

               9. Bone marrow or solid organ transplantation

          -  Other significant medical condition that may require intervention during the study

        Exclusions Based on Concurrent Medication Use

          -  Therapy with an immunomodulatory agent

          -  Use of telbivudine

          -  Current use of heparin or Coumadin

          -  Received blood products within 30 days before study randomization

          -  Use of hematologic growth factors within 30 days before study randomization

          -  Systemic antibiotics, antifungals, or antivirals for treatment of active infection
             other than HBV within 14 days before study randomization

          -  Any prescription or herbal product that is not approved by the investigator

          -  Long-term treatment (> 2 weeks) with agents that have a high risk for nephrotoxicity
             or hepatotoxicity unless it is approved by the medical monitor

          -  Receipt of systemic immunosuppressive therapy within 3 months before screening