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Chronic Delta HepatitisPhase 2LOWR-5NCT02968641

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

A Phase 2 study testing Lonafarnib and Ritonavir in people with Chronic Delta Hepatitis, run by Eiger BioPharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Delta Hepatitis
What is being tested?
Lonafarnib and Ritonavir
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Start not givento 12 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to comply with study procedures and provide written consent
  • 18 - 65 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
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  • 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:
  • Surgical sterilization (vasectomy ≥ 1 month before screening) or
  • Both of the following contraceptive methods from screening:
  • Consistently and correctly use a condom
  • Partner must agree to use a hormonal contraceptive or a nonhormonal barrier method (IUD or diaphragm with spermicide or cervical cap with spermicide)

Who cannot join

  • General Exclusions
  • 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).
  • Exclusions Based on Disease
  • Current or previous history of decompensated liver disease (Child-Pugh Class B or C)
Show all 58Show fewer
  • 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
  • White blood cell (WBC) count < 3,000 cells/mm3
  • Absolute neutrophil count (ANC) < 1,500 cells/mm3
  • Hemoglobin
  • < 11 g/dL for women
  • < 12 g/dL for men
  • Serum creatinine concentration ≥ 1.5 × ULN
  • Confirmed creatinine clearance (CrCl) < 50 mL/min by Cockroft-Gault or an estimated glomerular filtration rate (eGFR) > 80 mL/min at screening, based on the Cockcroft-Gault equation
  • Alpha-fetoprotein ≥ 100 ng/mL
  • Evidence of another form of viral hepatitis or another form of liver disease (eg, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, alcoholic liver disease, nonalcoholic steatohepatitis, hemochromatosis, alpha-1-anti-trypsin deficiency)
  • History of hepatocellular carcinoma
  • Patients with any of the following:
  • Current eating disorder or alcohol abuse
  • Excessive alcohol intake, defined as follows:
  • > 20 g/day for females (1.5 standard alcohol drinks) or
  • > 30 g/day for males (2.0 standard alcohol drinks).
  • A standard drink contains 14 g of alcohol: 360 mL of beer, 150 mL of wine, or 45 mL of spirits
  • In the opinion of the investigator, an alcohol use pattern that will interfere with study conduct
  • Drug abuse within the previous 6 months before screening, with the exception of cannabinoids and their derivatives
  • Prior history or current evidence of any of the following:
  • Immunologically mediated disease (eg, rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) that requires more than intermittent nonsteroidal anti-inflammatory medications for management or that requires use of systemic corticosteroids in the 6 months before screening (inhaled asthma medications are allowed)
  • Retinal disorder or clinically relevant ophthalmic disorder
  • Any malignancy within 5 years before screening. Exceptions are superficial dermatologic malignancies (eg, squamous cell or basal cell skin cancer treated with curative intent), or successfully treated in-situ carcinoma of the cervix.
  • Cardiomyopathy or significant ischemic cardiac or cerebrovascular disease (including history of angina, myocardial infarction, or interventional procedure for coronary artery disease)
  • Chronic pulmonary disease (eg, chronic obstructive pulmonary disease) associated with functional impairment
  • Pancreatitis
  • Severe or uncontrolled psychiatric disorder (eg, depression, manic condition, psychosis, acute and/or chronic cognitive dysfunction, suicidal behavior, and relapse of substance abuse)
  • Bone marrow or solid organ transplantation
  • Other significant medical condition that may require intervention during the study. Patients with any serious condition that, in the opinion of the investigator, would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed. Patients for whom participation in the study would increase their risk.
  • Exclusions Based on Concurrent Medication Use
  • Any prescription or herbal product that is not approved by the investigator
  • Therapy with an immunomodulatory agent, IFN-alfa (IFN alfa-2a or IFN alfa-2b, or pegylated IFN alfa-2a or alfa-2b), cytotoxic agent, or systemic corticosteroids within 12 months before screening and during the study
  • Use of heparin or warfarin during the study
  • Systemic antibiotics, antifungals, or antivirals for treatment of active infection other than HBV within 14 days before study randomization or during the study
  • Long-term treatment (> 2 weeks) before or during the study with agents that have a high risk for nephrotoxicity or hepatotoxicity unless it is approved by the medical monitor
  • Receipt of systemic immunosuppressive therapy within 3 months before screening or during the study
  • History or evidence for any intolerance or hypersensitivity to LNF, RTV, or other substances that are part of the study drug
  • Concomitant use of any of the following:
  • Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4
  • Drugs known to prolong the PR or QT interval unless otherwise described in this protocol
  • Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
  • Concomitant use of medications contraindicated in the prescribing information for RTV

About this study

Official title: 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 (LOWR-5)

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

Read the detailed description

This Phase 2b, randomized, open-label study will assess the safety, tolerability, and pharmacodynamics (PD)/efficacy of 48 weeks of lonafarnib (LNF) and ritonavir (RTV) combination therapy vs. LNF monotherapy in patients with chronically infected with Hepatitis Delta Virus (CHD). Sixty patients will be enrolled at a single study site. Eligible patients will have CHD infection (≥ 6 months) confirmed by positive HDV antibody (Ab) test and HDV RNA ≥ 3 lg IU/mL by quantitative polymerase chain reaction (qPCR) at study entry.

Being tested
Lonafarnib, Ritonavir
Medical subject headings
Hepatitis D, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LonafarnibDrug

    Also called EBP994, Sarasar

    antiviral farnesyltransferase inhibitor

  • RitonavirDrug

    Also called Norvir

    CYP 3A4 inhibitor, lonafarnib booster

Study groups in NCT02968641
Study groupRoleWhat they receive
LNF 25 mg bid and RTV 100 mg bidActive comparatorPatients 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.
Receives: Drug: Lonafarnib; Drug: Ritonavir
LNF 50 mg bid and RTV 100 mg bidActive comparatorPatients 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.
Receives: Drug: Lonafarnib; Drug: Ritonavir
LNF 100 mg bidActive comparatorPatients 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.
Receives: Drug: Lonafarnib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 72 weeks

Secondary outcomes (7)

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

    Measured: 48 weeks

  2. Proportion of patients with histological response

    Histological response defined as an improvement in liver histology by at least 2 points in the Hepatitis Activity Score (HAI) with improvement or no worsening of the fibrosis score, at the EOT compared with baseline

    Measured: 72 weeks

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

    Measured: 60 weeks

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

    Measured: 72 weeks

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

    Measured: 48 weeks

  6. Number of participants with treatment-emergent / treatment-related adverse events (AE) and serious adverse events

    Measured: 48 weeks

  7. Number of participants with AE leading to early discontinuation of study treatment or dose reduction

    Measured: 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2016 (estimated)
  2. Primary completion12 Feb 2021

Why it stopped: This study was initially planned to enroll patients in Mongolia. However, due to challenges in setting it up in Mongolia, this study was later determined not to be initiated.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02968641
Sponsor's protocol ID
EIG-LNF-004
Acronym
LOWR-5
Status last verified
Feb 2021
First submitted
15 Nov 2016
Last updated
16 Feb 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 26189433

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lonafarnib and Ritonavir in people with Chronic Delta Hepatitis, run by Eiger BioPharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 58 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 16 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline in HDV viral load at Week 72 visit (end of follow-up) (time frame: 72 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02968641, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2021.

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