Proof-of-concept Study Evaluating the Safety and Efficacy of EBP921 in Delta Hepatitis (HDV)

An Open Label, Dose-ranging Proof-of-concept Study Assessing the Safety and Efficacy of EBP921 in Therapy-naive Patients Chronically Infected With Delta Hepatitis (HDV)

The purpose of this study is to assess the optimal dose of EBP921 by comparing the efficacy and safety of 2 dose regimens in patients with chronic HDV.

Study Overview

• Status: Terminated
• Conditions: Hepatitis D
• Intervention / Treatment: Drug: EBP921

Detailed Description

This is an open-label, phase 1b, proof-of-concept study to assess the safety and efficacy of EBP921, a prenylation inhibitor, in subjects chronically infected with delta hepatitis. Subjects will be randomized to receive one of two different doses of EBP921. Dosing will occur over 28-days and during that time, evidence of antiviral response will be assessed by frequent measurements of HDV-RNA via PCR assay. In addition, safety lab data will also be collected along with surveillance monitoring of HBV activity.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women age 18 or older with the capacity to give written informed consent
2. Patients with compensated chronic HDV infection as indicated by presence of anti-HDV in serum.
3. Liver biopsy should be performed within one-year of study screening and graded using the Knodell scoring system.
4. Presence of HDV antigen in liver tissue or HDV-RNA in serum.
5. Active HBV replication will not exclude patients.
6. Previous therapy with standard alpha-interferon or peginterferon will not exclude patients.
7. Patients who are HBV therapy-naïve or who previously received HBV antiviral therapy will be eligible. Patients currently taking HBV antiviral therapy will e considered on a case basis.
8. Female subjects of reproductive potential and female partners of male subjects should be on two reliable forms of contraception from the start of the study until 60 days from the end of EBP921 dosing.

Exclusion Criteria:

1. Severe neuropsychiatric disorders
2. History or clinical manifestations of significant metabolic, hematological, pulmonary, ischemic heart disease, significant or unstable heart disease, gastrointestinal, neurological, renal, urological, endocrine, ophthalmologic disorders including severe retinopathy, or immune-mediated disease
3. Pregnant or breast-feeding patients or the inability to practice adequate contraception during the conduct of the study
4. Underlying autoimmune/immune-deficiency disease (e.g., lupus, sarcoidosis, celiac disease, HIV antibody positive, AIDS)
5. Chronic (> 4 weeks duration) diarrhea
6. Body weight > 128 kg and < 40 kg
7. Uncompensated cirrhosis
8. Absolute neutrophil count less than 1500 per cubic millimeter
9. Platelet count less than 90,000 per cubic millimeter
10. Evidence of concurrent HCV infection with positive serum HCVRNA
11. Evidence of hepatocellular carcinoma
12. Active substance abuse (alcohol, inhaled or injected drugs) within the past 12 months
13. Diagnosis of malignancy in the previous five years excluding superficial dermatologic malignancies
14. Any experimental therapy in the previous 6 months prior to enrollment.

16. Patients with a history of multiple drug resistant HBV 17. Patients receiving interferon therapy for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Low Dose for 28 days: n=4	Drug: EBP921; Patients randomized to receive low or high dose. All dosing of EBP921 should be taken with food.
Experimental: Group 2; High Dose for 28 days; n=4	Drug: EBP921; Patients randomized to receive low or high dose. All dosing of EBP921 should be taken with food.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HDV-RNA	The primary efficacy endpoint will be the median change in HDV-RNA from baseline to HDV RNA nadir as measured by quantitative PCR during the 28-day dosing period.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HDV RNA from baseline to Day 7, 14, 28 and post therapy weeks 1,2,4,8	The median change in HDV RNA from baseline to Days 7, 14, 28, and post-therapy Weeks 1, 2, 4, and 8 of the study; the proportion of patients with alanine aminotransferase (ALT) normalization defined as ALT ≤ upper limit of normal for patients with ALT > ULN at baseline; assessment of peripheral blood mononuclear cell (PBMC) proliferation after 14 and 28 days exposure to EBP921; the percentage of patients with undetectable HDV RNA at Days 7, 14, 28, post-therapy Weeks 1, 2, 4, and 8; the median change in HBV DNA at Days 7, 14, 21, 28, 35, and 42, and HBsAg at Days 14, 28, and 42.	8 Weeks

Collaborators and Investigators

• Sponsor: Eiger BioPharmaceuticals
• Investigators: Study Director: Brian Murphy, MD, MPH, Eiger BioPharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): August 8, 2016
• Last Update Submitted That Met QC Criteria: August 4, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Hepatitis; Hepatitis D; HDV
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis D
• Other Study ID Numbers: EBP-HDV 01-921-01