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Lonafarnib With Ritonavir in HDV (LOWR-2) (LOWR-2)

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ClinicalTrials.gov Identifier: NCT02430194
Recruitment Status : Completed
First Posted : April 30, 2015
Last Update Posted : July 31, 2017
Sponsor:
Collaborator:
Ankara University
Information provided by (Responsible Party):
Eiger BioPharmaceuticals

Brief Summary:
An Open-label, Dose-ranging Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-2).

Condition or disease Intervention/treatment Phase
Chronic Hepatitis D Infection Drug: lonafarnib Drug: Ritonavir Drug: PEG IFN-a Phase 2

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 forty-five subjects with chronic delta hepatitis will be randomized to receive one of nine 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 PEG IFN-alpha.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Dose-ranging, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Lonafarnib With Ritonavir-Boosting in Patients Chronically Infected With Delta Hepatitis (HDV) (LOWR-2)
Actual Study Start Date : December 2014
Actual Primary Completion Date : April 18, 2017
Actual Study Completion Date : June 15, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Ritonavir

Arm Intervention/treatment
Experimental: lonafarnib/ritonavir - I
lonafarnib 100 mg BID + ritonavir 100 mg QD;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Experimental: lonafarnib/ritonavir - II
lonafarnib 150 mg QD + ritonavir 100 mg QD;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Experimental: lonafarnib/ritonavir - III
lonafarnib 75 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW on Week 12
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Drug: PEG IFN-a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-alpha
  • Pegylated interferon-alpha-2a

Experimental: lonafarnib/ritonavir - IV
lonafarnib 50 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW on Week 12
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Drug: PEG IFN-a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-alpha
  • Pegylated interferon-alpha-2a

Experimental: lonafarnib/ritonavir - V
lonafarnib 100 mg BID + ritonavir 50 mg BID;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Experimental: lonafarnib/ritonavir - VI
lonafarnib 100 mg QD + ritonavir 100 mg QD;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Experimental: lonafarnib/ritonavir - VII
lonafarnib 50 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Drug: PEG IFN-a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-alpha
  • Pegylated interferon-alpha-2a

Experimental: lonafarnib/ritonavir/PEG IFN-a - VIII
lonafarnib 25 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW;
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Drug: PEG IFN-a
immunomodulator
Other Names:
  • Pegasys
  • PEG IFN-alpha
  • Pegylated interferon-alpha-2a

Experimental: lonafarnib/ritonavir/PEG IFN-a - IX
lonafarnib 50 mg BID + ritonavir 100 mg BID
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir

Experimental: lonafarnib/ritonavir - X
lonafarnib 25 mg BID + ritonavir 100 mg BID
Drug: lonafarnib
antiviral farnesyl transferase inhibitor
Other Name: Sarasar, EBP994

Drug: Ritonavir
CYP 3A4 inhibitor, lonafarnib booster
Other Name: Norvir




Primary Outcome Measures :
  1. Decline of HDV RNA from baseline to end of treatment with lonafarnib and ritonavir [ Time Frame: 12-48 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. abstinence
    2. surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six months minimum
    3. IUD in place for at least six months
    4. barrier methods (condom or diaphragm) with spermicide
    5. surgical sterilization of the partner (vasectomy for six months)
    6. 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

Exclusion Criteria:

  • 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
  • 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/mm3; platelet count < 100,000 cells/mm3; 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:

    1. variceal bleeding, ascites, hepatic encephalopathy, CTP score > 6, decompensated liver disease or any other form of non-viral hepatitis
    2. 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)
    3. any malignancy within 3 years except for basal cell skin cancer
    4. significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)
    5. chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) associated with functional impairment
    6. 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/m2
  • Concomitant drugs known to prolong the QT interval

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02430194


Locations
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Turkey
Ankara University Medical School
Ankara, Turkey
Sponsors and Collaborators
Eiger BioPharmaceuticals
Ankara University
Investigators
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Principal Investigator: Cihan Yurdaydin, MD Ankara University
Additional Information:
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Responsible Party: Eiger BioPharmaceuticals
ClinicalTrials.gov Identifier: NCT02430194    
Other Study ID Numbers: EIG-300-Amendment 3
First Posted: April 30, 2015    Key Record Dates
Last Update Posted: July 31, 2017
Last Verified: July 2017
Additional relevant MeSH terms:
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Hepatitis D
Hepatitis D, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Hepatitis, Chronic
Interferons
Ritonavir
Interferon-alpha
Interferon alpha-2
Peginterferon alfa-2a
Lonafarnib
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs