A Study of Lonafarnib With or Without Ritonavir in Patients With HDV

NCT02968641 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: EIG-LNF-004
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Phase 2b, Open-Label, Randomized Study of the Safety, Tolerability, and Pharmacodynamic Activity of Lonafarnib With or Without Ritonavir in Patients Chronically Infected with Hepatitis Delta Virus

Conditions

Chronic Delta Hepatitis

Outcome Measures

Primary Outcomes (1)

• Change from baseline in HDV viral load at Week 72 visit (end of follow-up)

  HDV RNA viral load will be quantified with a real-time qPCR assay with a lower limit of quantification (LLOQ) of 14 IU/mL

  72 weeks

Secondary Outcomes (7)

• Change from baseline in HDV viral load at Week 48 visit (end of treatment, EOT)

  48 weeks

• Proportion of patients with histological response

  72 weeks

• Proportion of patients with sustained virologic response: HDV RNA below the LLOQ 12 weeks after EOT (48 weeks)

  60 weeks

• Proportion of patients with sustained virologic response: HDV RNA below the LLOQ 24 weeks after EOT (48 weeks)

  72 weeks

• Number of participants with treatment-emergent changes in clinical laboratory findings

  48 weeks

Study Arms (3)

LNF 25 mg bid and RTV 100 mg bid

ACTIVE COMPARATOR

Patients will take lonafarnib 25 mg BID and ritonavir 100 mg BID. Patients will also take an anti-hepatitis B virus (HBV) nucleos(t)ide analog (NUC) from the first dose of LNF through the end of the study.

Drug: Lonafarnib; Drug: Ritonavir

LNF 50 mg bid and RTV 100 mg bid

ACTIVE COMPARATOR

Patients will take lonafarnib 50 mg BID and ritonavir 100 mg BID. Patients will also take an anti-hepatitis B virus (HBV) nucleos(t)ide analog (NUC) from the first dose of LNF through the end of the study.

Drug: Lonafarnib; Drug: Ritonavir

LNF 100 mg bid

ACTIVE COMPARATOR

Patients will take lonafarnib 100 mg BID. Patients will also take an anti-hepatitis B virus (HBV) nucleos(t)ide analog (NUC) from the first dose of LNF through the end of the study.

Drug: Lonafarnib

Interventions

Lonafarnib DRUG

antiviral farnesyltransferase inhibitor

Also known as: EBP994, Sarasar

LNF 100 mg bid; LNF 25 mg bid and RTV 100 mg bid; LNF 50 mg bid and RTV 100 mg bid

Ritonavir DRUG

CYP 3A4 inhibitor, lonafarnib booster

Also known as: Norvir

LNF 25 mg bid and RTV 100 mg bid; LNF 50 mg bid and RTV 100 mg bid

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to comply with study procedures and provide written consent
• years old
• Body mass index (BMI) of ≥ 18 kg/m2 and weighs ≥ 45 kg
• CHD infection of at least 6 months' duration documented by a positive HDV antibody (Ab) test and HDV RNA ≥ 3 log10/mL by qPCR at study entry
• Serum ALT \> upper limit of the normal range (ULN) and \< 10 × ULN
• Liver biopsy within 12 months of Day 1 demonstrating evidence of chronic hepatitis. If no liver biopsy is available, the patient must be willing to consent to and have no contraindication to liver biopsy
• ECGs 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
• Dilated retinal examination ≤ 1 year before screening: For patients with diabetes, hypertension, or other risk factors for retinal disease, performed by a licensed ocular specialist; for all other patients, a normal retinal examination as assessed by the investigator or a licensed ocular specialist
• 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 for 90 days after the last dose of study drug. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal.
• For females: 2 of the following contraceptive methods, with at least 1 being a barrier method:
• Hormonal contraceptives for ≥ 3 months before screening
• Intrauterine device (IUD) in place ≥ 3 months before screening
• Double-barrier methods (use of condom \[male partner\] with either diaphragm with spermicide or cervical cap with spermicide) from screening
• Surgical sterilization of the partner (vasectomy ≥ 1 month before screening)
• For males:

You may not qualify if:

• Participation in a clinical trial with, or use of, any investigational agent within 30 days before screening
• Previous use of LNF.
• Female patients who are pregnant or breastfeeding. Male patients must confirm that their female sexual partners are not pregnant. Female patients must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[hCG\]) within 24 hours prior to the start of any investigational agent).
• 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).
• Positive results for HIV or HCV Ab at screening. Patients with a positive HCV Ab at screening are allowed if they have completed a curative antiviral regimen and have documented undetectable HCV RNA for at least 3 months before screening and at screening.
• Past history or current evidence of decompensated liver disease, defined as any of the following at screening:
• Bilirubin level ≥ 2.5 mg/dL unless due to Gilbert's disease
• Serum albumin level \< 3.0 g/dL
• International normalized ratio (INR) ≥ 1.5
• Evidence of significant portal hypertension such as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg; current presence or history of esophageal or abdominal varices, variceal bleeding, or splenomegaly \> 12 cm length on imaging
• Current evidence or history of ascites requiring diuretics or paracentesis, or hepatic encephalopathy
• Current evidence or history of hepatic encephalopathy
• Any of the following abnormal laboratory test results at screening:
• Platelet count \< 90,000 cells/mm3

Sponsors & Collaborators

• Eiger BioPharmaceuticals: lead

Related Publications (2)

• Koh C, Canini L, Dahari H, Zhao X, Uprichard SL, Haynes-Williams V, Winters MA, Subramanya G, Cooper SL, Pinto P, Wolff EF, Bishop R, Ai Thanda Han M, Cotler SJ, Kleiner DE, Keskin O, Idilman R, Yurdaydin C, Glenn JS, Heller T. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015 Oct;15(10):1167-1174. doi: 10.1016/S1473-3099(15)00074-2. Epub 2015 Jul 16.

  PMID: 26189433 BACKGROUND

• Yurdaydin C, et al. Optimizing the Prenylation Inhibitor Lonafarnib Using Ritonavir Boosting in Patients with Chronic Delta Hepatitis. EASL 2015, Abstract 0118.

  BACKGROUND

Related Links

• Eiger BioPharmaceuticals, Inc. company website

MeSH Terms

Conditions

Hepatitis D, Chronic

Interventions

lonafarnib; Ritonavir

Condition Hierarchy (Ancestors)

Hepatitis D; Hepatitis, Viral, Human; Virus Diseases; Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Eduardo B Martins, MD, DPhil

  Eiger BioPharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: November 18, 2016
• Primary Completion: February 12, 2021
• Last Updated: February 16, 2021

Record last verified: 2021-02