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Chronic Hepatitis D InfectionPhase 2LOWR-2NCT02430194

Lonafarnib Boosted With Ritonavir With and Without Peginterferon Alfa-2a (PEG IFN-a) in HDV (LOWR-2)

A Phase 2 study testing lonafarnib, ritonavir and Pegylated interferon-alfa-2a in people with Chronic Hepatitis D Infection, run by EIT Pharma, Inc. at 1 site in Turkey (Türkiye).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

An Open-label, Dose-ranging Study to Evaluate the Safety and Efficacy of Lonafarnib with Ritonavir Boosting +/- Peginterferon alfa-2a in Patients Chronically Infected with Delta Hepatitis (HDV) (LOWR-2). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Hepatitis D Infection
What is being tested?
lonafarnib, ritonavir and Pegylated interferon-alfa-2a
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
1 siteTurkey (Türkiye)
Study dates
Dec 2014to 15 Jun 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Males or females, 18 to 65 years of age who are diagnosed with HDV by PCR
  • Chronic hepatitis D infection, genotype 1, documented by a positive anti-HDV Ab test at least of 6 months duration and detectable HDV RNA by PCR within 3 months to study entry
  • Liver biopsy within the last two years (biopsy can be done at the Screening Visit)
  • Positive viral load of >100,000 copies/mL as measured by quantitative PCR
  • Electrocardiogram (ECG) shows no acute ischemia or clinically significant abnormality and a QT/QTc interval <450 milliseconds - using Bazett's correction
  • Females of childbearing potential (intact uterus and within 1 year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, these subjects should agree to use one of the following acceptable birth control methods throughout the study:
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  • abstinence
  • surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum
  • IUD in place for at least six months
  • barrier methods (condom or diaphragm) with spermicide
  • surgical sterilization of the partner (vasectomy for six months)
  • hormonal contraceptives for at least three months prior to the first dose of study drug
  • Willing and able to comply with study procedures and provide written informed consent

Who cannot join

  • Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1
  • Patients co-infected with HIV
  • Patients with screening tests positive for HCV, or anti-HIV Ab
  • History of decompensated cirrhosis within the past year
  • Active jaundice defined by total bilirubin > 2.0 excluding Gilbert's disease
  • INR ≥ 1.5
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  • Eating disorder or alcohol abuse within the past 2 years, excessive alcohol intake (> 20 g per day for females (1.5 standard alcohol drinks) or > 30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL)
  • Drug abuse within the last six months with the exception of cannabinoids and their derivatives
  • Patients with absolute neutrophil count (ANC) < 1500 cells/mm^3; platelet count < 100,000 cells/mm^3; hemoglobin < 12 g/dL for women and < 13 g/dL for men; abnormal TSH,T4, or T3 or thyroid function not adequately controlled; or serum creatinine concentration ≥ 1.5 times upper limit of normal (ULN)
  • History or clinical evidence of any of the following:
  • variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6, decompensated liver disease or any other form of non-viral hepatitis
  • immunologically mediated disease (e.g., rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent nonsteroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed)
  • any malignancy within 3 years except for basal cell skin cancer
  • significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
  • chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
  • severe or uncontrolled psychiatric disease, including severe depression, history of suicidal ideation, suicidal attempts or psychosis requiring medication and/or hospitalization 2
  • Patients with a body mass index > 30 kg/m^2
  • Concomitant drugs known to prolong the QT interval

Trial locations and contacts

1 site in 1 country.

Turkey (Türkiye)1 site

  • Ankara University Medical School

    Ankara

Other trials in Turkey (Türkiye)

About this study

Official title: An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir-Boosting +/- Peginterferon Alfa-2a in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-2)

An Open-label, Dose-ranging Study to Evaluate the Safety and Efficacy of Lonafarnib with Ritonavir Boosting +/- Peginterferon alfa-2a in Patients Chronically Infected with Delta Hepatitis (HDV) (LOWR-2).

Read the detailed description

Chronic delta hepatitis is a serious form of chronic liver disease caused by infection with the hepatitis D virus (HDV), a small RNA virus that requires farnesylation of its major structural protein (HDV antigen) for replication. Up to sixty subjects with chronic delta hepatitis will be randomized to receive one of ten different doses of lonafarnib. Dosing will occur over 12-48 weeks, and during that time, evidence of antiviral response will be assessed by frequent measurements of HDV-RNA. The primary therapeutic endpoint will be an improvement in quantitative serum HDV RNA levels after treatment with lonafarnib therapy. The primary safety endpoint will be the ability to tolerate the drug at the prescribed dose for the treatment duration. Several secondary endpoints will be measured, including side effects, ALT levels, and symptoms. Therapy will be stopped for intolerance to lonafarnib. This study is designed as a Phase 2a study assessing the safety, tolerance and antiviral activity of nine dosing combinations of lonafarnib with ritonavir boosting with and without peginterferon alfa-2a (PEG IFN-a).

Being tested
lonafarnib, ritonavir, Pegylated interferon-alfa-2a

What participants receive

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

  • lonafarnibDrug

    Also called Sarasar, EBP994, LNF

    antiviral farnesyl transferase inhibitor

  • ritonavirDrug

    Also called Norvir, RTV

    CYP 3A4 inhibitor, lonafarnib booster

  • Pegylated interferon-alfa-2aDrug

    Also called Pegasys, PEG IFN-alfa-2a, Peginterferon alfa-2a, PEG IFN-a

    immunomodulator

Study groups in NCT02430194
Study groupRoleWhat they receive
lonafarnib/ritonavir - IExperimentallonafarnib 100 mg BID + ritonavir 100 mg QD
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir - IIExperimentallonafarnib 100 mg BID + ritonavir 50 mg BID
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir - IIIExperimentallonafarnib 100 mg QD + ritonavir 100 mg QD
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir - IVExperimentallonafarnib 150 mg QD + ritonavir 100 mg QD
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir/PEG IFN-a - VExperimentallonafarnib 75 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
Receives: Drug: lonafarnib; Drug: ritonavir; Drug: Pegylated interferon-alfa-2a
lonafarnib/ritonavir - VIExperimentallonafarnib 25 mg BID + ritonavir 100 mg BID
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir - VIIExperimentallonafarnib 50 mg BID + ritonavir 100 mg BID
Receives: Drug: lonafarnib; Drug: ritonavir
lonafarnib/ritonavir/PEG IFN-a - VIIIExperimentallonafarnib 50 mg BID + ritonavir 100 mg BID (+ PEG IFN-a 180 ug QW on Week 12)
Receives: Drug: lonafarnib; Drug: ritonavir; Drug: Pegylated interferon-alfa-2a
lonafarnib/ritonavir/PEG IFN-a - IXExperimentallonafarnib 25 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
Receives: Drug: lonafarnib; Drug: ritonavir; Drug: Pegylated interferon-alfa-2a
lonafarnib/ritonavir/PEG IFN-a - XExperimentallonafarnib 50 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW
Receives: Drug: lonafarnib; Drug: ritonavir; Drug: Pegylated interferon-alfa-2a

What is being measured

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

  1. ≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT)

    Proportion of intent to treat patients with ≥2 log10 decline of HDV RNA from baseline at end of treatment (EOT)

    Measured: 12-48 weeks

Secondary outcomes (2)

  1. < LLOQ in HDV RNA at End of Treatment (EOT)

    Proportion of intent to treat patients with HDV RNA below the limit of quantitation at end of treatment

    Measured: 12-48 weeks

  2. ALT Normalization at End of Treatment

    Proportion of intent to treat population who normalize ALT at end of treatment

    Measured: 12-48 weeks

Timeline

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

  1. First posted30 Apr 2015 (estimated)
  2. Study startDec 2014
  3. Primary completion18 Apr 2017
  4. Study completion15 Jun 2017

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
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02430194
Sponsor's protocol ID
EIG-300-Amendment 3
Acronym
LOWR-2
Status last verified
Mar 2023
First submitted
21 Apr 2015
Last updated
25 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Yurdaydin C, Keskin O, Yurdcu E, Caliskan A, Onem S, Karakaya F, Kalkan C, Karatayli E, Karatayli S, Choong I, Apelian D, Koh C, Heller T, Idilman R, Bozdayi AM, Glenn JS. A phase 2 dose-finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis. Hepatology. 2022 Jun;75(6):1551-1565. doi: 10.1002/hep.32259. Epub 2021 Dec 23.

    PubMed 34860418

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lonafarnib, ritonavir and Pegylated interferon-alfa-2a in people with Chronic Hepatitis D Infection, run by EIT Pharma, Inc. at 1 site in Turkey (Türkiye).

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 13 inclusion and 18 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: finished, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

≥2 log10 Decline of HDV RNA From Baseline at End of Treatment (EOT) (time frame: 12-48 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 NCT02430194, which also lists 1 linked publication.

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 25 Sep 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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