Efficacy of All-Oral Anti-Viral Therapy for Symptomatic Hepatitis C Virus Infection-Related Cryoglobulinemia

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.

• Willing and able to provide written informed consent
• Male or female, age ≥18 years
• HCV RNA ≥ 15 IU/mL at Screening
• HCV genotype 1
• Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy
• Classification as treatment naïve or treatment experienced:
• Treatment naïve is defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents or prior treatment of HCV with interferon or ribavirin or DAAs (except for SOF-containing regimens).
• Treatment experienced is defined as prior treatment failure or relapse to a regimen containing interferon either with or without RBV or DAAs (except for SOF-containing regimens) that was completed at least 8 weeks prior to Baseline/Day 1.

The subject's medical records must include sufficient detail of prior virologic failure to allow for categorization of prior response, as either:

• Non-Responder: Subject did not achieve undetectable HCV RNA levels while on treatment, or
• Relapse/Breakthrough: Subject achieved undetectable HCV RNA levels during treatment or within 4 weeks of the end of treatment but did not achieve SVR.
• Cirrhosis determination (approximately 20% of subjects may have cirrhosis) a. Cirrhosis is defined as any one of the following:

i) Any previous liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥5) ii) FibroMeter® score >0.442 or an AST:platelet ratio index (APRI) >2 during Screening iii) Fibroscan with a result of >12.5 kPa at any time prior to or during screening.

b. Absence of cirrhosis is defined as any one of the following: i) Liver biopsy within 2 years of Screening showing absence of cirrhosis ii) FibroMeter® score 60-70% average for age.

i. WBC >1500 /uL ii.Platelets > 50,000/uL

d) Direct bilirubin >2 x ULN e) INR >1.5 x ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR

• Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Baseline/Day 1 prior to treatment.
• Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
• Lactating females must agree to discontinue nursing before the study drug is administered.
• Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator.
• Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.

Note: Definition of Mixed Cryoglobulinemia (patients must meet one of the five overlapping syndromes listed below and the presence of cold-precipitable immune complexes in blood on two different occasions.

• Clinical evidence of cryoglobulinemia, overlapping syndromes:
• Cutaneous vasculitis (Raynaud's phenomenon, purpura, skin ulcers, livedo, acrocyanosis)
• Glomerulonephritis (hypertension, hematuria, nephrotic syndrome)
• Arthropathy (arthralgias, arthritis)
• Neuropathy (peripheral and/or central nervous system, distal sensorimotor, mononeuritis multiplex)
• Sicca syndrome (xerostomia, xerophthalmia)

Other factors that will be assessed / recorded in patients with MC will be:

• Associated laboratory abnormalities including:
• Positive HCV serology (recombinant immunoblot assay), viral nucleic acid quantitation diagnostic for HCV infection, and reflex genotyping.
• Evidence of glomerulonephritis, including an active urinary sediment, hypoalbuminemia (albumin 300mg/day).
• Abnormal nerve conduction testing. 2. Pathologic evidence of cryoglobulinemia including:
• Leukocytoclastic vasculitis.
• Membranoproliferative glomerulonephritis.
• Vasculopathy and/or mononuclear cell infiltrates on sural nerve biopsy.
• Lip biopsy suggestive