Chronic Delta HepatitisPhase 2LOWR-4NCT02527707
Titrating-Dose of Lonafarnib in Combination With Ritonavir
A Phase 2 study testing lonafarnib and Ritonavir in people with Chronic Delta Hepatitis, run by EIT Pharma, Inc..
Trial summary
A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV) 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
- 15 participants
- Where
- No sites listed yet
- Study dates
- Sep 2015to 9 Feb 2017
- Phase
- Phase 2
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
- Male or female, 18 to 65 years of age, inclusive
- Chronic HDV infection documented by a positive HDV antibody (Ab) test of at least 6 months duration and detectable HDV ribonucleic acid (RNA) by quantitative polymerase chain reaction (qPCR) at study entry
- Liver biopsy demonstrating evidence of chronic hepatitis
- Willingness to practice appropriate contraception
Who cannot join
- Previous use of lonafarnib
- Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
- Active jaundice defined by total bilirubin level >2.0 mg/dL and known not to have Gilbert's disease
- Decompensated liver disease or cirrhosis, history of bleeding esophageal varices, ascites, or hepatic encephalopathy
- Serum creatinine concentration ≥1.5 times upper limit of normal (ULN)
- Evidence of another form of viral hepatitis (not including hepatitis B virus or HCV) or another form of liver disease
Show all 14Show fewer
- Evidence of hepatocellular carcinoma
- Use of alfa interferon, either interferon alfa-2a or interferon alfa-2b, or peginterferon alfa-2a within 2 months before the start of screening
- Concomitant use of any of the following:
- Medications or foods that are known moderate or strong inducers or inhibitors of CYP3A4 or CYP2C19
- Drugs known to prolong the PR interval or QT interval of the electrocardiogram
- Receipt of systemic immunosuppressive therapy within the 3 months before start of screening
- Statins, due to inhibition of mevalonate synthesis, which reduces protein prenylation
- Medications contraindicated in the prescribing information for ritonavir
About this study
Official title: A Phase 2, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Activity of a Titrating-Dose Lonafarnib/Ritonavir in Patients Chronically Infected With Hepatitis Delta Virus
A phase 2, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic activity of titrating-dose lonafarnib/ritonavir in patients chronically infected with hepatitis delta virus (HDV)
Read the detailed description
This is a Phase 2 study of 24 weeks of treatment with a dose-titration regimen of lonafarnib/ritonavir in up to 15 patients chronically infected with HDV: lonafarnib starting at 50 mg twice daily (BID) in combination with ritonavir 100 mg BID and escalating lonafarnib as tolerated.
The duration of the study for each patient is approximately 13 months (up to 4 weeks for screening, 24 weeks of treatment, 4 weeks for the primary follow-up visit, and monthly safety follow-up visits for 5 months thereafter). The 6-month follow-up after the last dose of study drug is designed to allow evaluation of the clinical and virologic course after completion of the 24-week Treatment Period.
- Conditions
- Chronic Delta Hepatitis
- 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
Cytochromes P450 3A4 inhibitor used to boost lonafarnib
| Study group | Role | What they receive |
|---|---|---|
| lonafarnib/ritonavir | Experimental | Lonafarnib starting at 50 mg BID in combination with ritonavir 100 mg BID and escalating to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The duration of the study for each patient is 6 months of treatment and 6 months follow-up. Receives: Drug: lonafarnib; Drug: Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer
Change from baseline to Week 24 in mean HDV RNA titer following dose escalating from lonafarnib 50 mg BID to 75 mg BID and to 100 mg BID, all boosted with ritonavir 100 mg BID.
Measured: Baseline and Week 24 (6 months)
Secondary outcomes (1)
Number of Patients With 1 Log Reduction From Baseline by Timepoint
Number of patients with at least 1 log reduction in HDV RNA from baseline by dose level and timepoint
Measured: Baseline and Week 1, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 20, or Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2015 (estimated)
- Study startSep 2015
- Primary completionAug 2016
- Study completion9 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic Delta HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- EIT Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hannover Medical School
- Responsible party
- Sponsor
- Investigators
- Heiner Wedemeyer, MD, PhD, Principal investigator, Hannover Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02527707
- Sponsor's protocol ID
- EIG-LNF-002
- Acronym
- LOWR-4
- Status last verified
- May 2023
- First submitted
- 13 Aug 2015
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
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 26189433Yurdaydin C, Keskin O, Kalkan C, Karakaya F, Caliskan A, Karatayli E, Karatayli S, Bozdayi AM, Koh C, Heller T, Idilman R, Glenn JS. Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study. Hepatology. 2018 Apr;67(4):1224-1236. doi: 10.1002/hep.29658. Epub 2018 Feb 19.
PubMed 29152762Yurdaydin 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