Clinical Trial: Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of Chronic Delta Hepatitis With Lonafarnib and Ritonavir

Brief Summary:

Background:

- Chronic hepatitis D is a liver disease caused by the hepatitis D virus. It can be severe and progressive. Most people with hepatitis D will develop scarring and damage to the liver. There is no FDA approved drug to treat chronic hepatitis D. Researchers want to know if the drugs lonafarnib and ritonavir can help people with chronic hepatitis D.

Objective:

- To find out if treatment of hepatitis D with lonafarnib and ritonavir is safe and effective.

Eligibility:

- People 18 years of age and older with chronic hepatitis D. They must not have HIV or other major illnesses.

Design:

  • Participants will be screened with medical history, physical exams, and blood tests.
  • Participants will have 24 weeks of treatment. They will then have 24 weeks of follow-up.
  • Participants will be in 1 of 6 treatment groups. Those in each group will receive different doses of the study drugs. Some groups will start with placebo but will receive treatment after 3 months of placebo.
  • Participants will also take drugs to treat hepatitis B.
  • Participants will have many visits. These will include:
  • One three-day stay at the Clinical Center
  • Physical exams
  • EKG: small sticky patches will be put on the chest, arms, and legs to trace heart rhythm
  • Ultrasounds of the abdomen
  • Primary Therapeutic Endpoint: Decline of HDV RNA Quantitative Measurements of >2 logs from baseline at 12 and 24 weeks of therapy with lonafarnib and ritonavir. [ Time Frame: 12 and 24 weeks ]
  • The ability to tolerate lonafarnib and ritonavir at the prescribed dose for 12 and 24 weeks of therapy. [ Time Frame: 12 and 24 weeks ]


Original Primary Outcome:

  • Primary Therapeutic Endpoint: Decline of HDV RNA Quantitative Measurements of & gt; 2 logs from baseline at 12 and 24 weeks of therapy with lonafarnib and ritonavir. [ Time Frame: 12 and 24 weeks ]
  • The ability to tolerate lonafarnib and ritonavir at the prescribed dose for 12 and 24 weeks of therapy. [ Time Frame: 12 and 24 weeks ]


Current Secondary Outcome:

  • Sustained undetectable HDV RNA in serum at weeks 12 and 24 of post-treatment follow-up. [ Time Frame: 12 and 24 wk post tx ]
  • Comparison of HDV RNA decline between 12 and 24 weeks of therapy at differing doses. [ Time Frame: End of dosing ]
  • Comparison of ALT changes between different doses of lonafarnib [ Time Frame: End of dosing ]
  • Loss of HBsAg from the serum at the end of therapy, at week 12 of post-therapy follow-up and at week 24 of post-therapy follow-up. [ Time Frame: 12 and 24 wk post tx ]
  • Changes in symptom scale measurements and quality of life before, during and after therapy. [ Time Frame: End of tx and study ]
  • Seroconversion of HBsAg at the end of therapy, at week 12 of post- therapy follow up and at week 24 of post-therapy follow-up. [ Time Frame: 12 and 24 wk post tx ]
  • Changes in the fecal microbiome before and after treatment [ Time Frame: End of dosing ]
  • Comparison of fecal microbiome analysis between different groups [ Time Frame: End of dosing ]
  • Undetectable HDV RNA in serum by quantitative measurements at the end of therapy. [ Time Frame: End of dosing ]
  • Comparison of serologic HDV RNA decline between different doses of lonafarnib [ Time Frame: End of dosing ]


Original Secondary Outcome: Same as current

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: July 29, 2015
Date Started: July 21, 2015
Date Completion:
Last Updated: April 20, 2017
Last Verified: February 23, 2017