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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

10 patients with chronic genotype 1 HCV infection and mixed cryoglobulinemia will be treated with Ledipasvir/Sofosbuvir 90mg/400 mg FDC once daily for 12 weeks (naïve subjects or non-cirrhotic treatment experienced subjects) or 24 weeks (treatment experienced subjects with cirrhosis).

The researchers anticipate that approximately 20% of subjects may have cirrhosis.

Detailed Summary:

The treatment of extrahepatic disease manifestations of HCV has largely paralleled that of hepatic disease. Interferon was reported to have efficacy for MC even before linkage of the syndrome to HCV in 1989, and successful combination therapy with ribavirin was found to eliminate virus and lead to the resolution of immunologic abnormalities associated with extrahepatic disease. In addition, ~75% of HCV-associated indolent asymptomatic lymphoproliferative diseases remit with successful antiviral therapy. However, in many instances, MC (notably cutaneous vasculitis) will relapse with recurrence of virus, and may occasionally persist even after clearance. In particular, side effects of Interferon alpha, including the uncovering of frank autoimmune disease, theoretically may mitigate response of extrahepatic disease to treatment. Peg-interferon increased the response rate of MC, and decreased the duration of treatment, but side effects remained problematic.

An alternative approach to the treatment of MC has been the use of immunomodulatory agents. In particular, B-cell expansion in peripheral blood and in lymphoid follicles in the liver prevalent amongst HCV-infected persons provided a rationale for the use of depletion as a therapeutic strategy. Rituximab (anti-CD20) monotherapy has been used mostly for treatment failures/intolerance or in the setting NHL, and has yielded response rates in the setting of involvement of skin (73%); MPGN (70%); joint (53%); and nerve (36%). However, this monoclonal antibody (MAb) has the potential to form immune-complexes with mixed cryoglobulin RF and cause clinical vasculitis in patients with high cryocrits, and may raise the HCV RNA level in rare patients, causing cytotoxicity. Following Rituximab with Peg-IFN plus ribavirin achieved greater than a 60% complete response (CR) in patients resistant to combination treatment alone. Other approa
Sponsor: Icahn School of Medicine at Mount Sinai

Current Primary Outcome:

• Sustained Virologic Response (SVR) [ Time Frame: up to 24 weeks after treatment ]
  proportion of subjects who attain SVR
• Response in patients with mixed cryoglobulinemia (MC) [ Time Frame: up to 24 weeks after treatment ]
  Response to medication in patients with MC categorized as either complete response vs partial response

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: July 3, 2016
Date Started: February 2016
Date Completion: February 2018
Last Updated: March 29, 2017
Last Verified: March 2017