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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

Tracking Information
First Submitted Date  ICMJE April 21, 2015
First Posted Date  ICMJE April 30, 2015
Last Update Posted Date July 31, 2017
Actual Study Start Date  ICMJE December 2014
Actual Primary Completion Date April 18, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2017)
Decline of HDV RNA from baseline to end of treatment with lonafarnib and ritonavir [ Time Frame: 12-48 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 25, 2015)
Decline of HDV RNA from baseline to end of treatment with lonafarnib and ritonavir [ Time Frame: 4-12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lonafarnib With Ritonavir in HDV (LOWR-2)
Official Title  ICMJE 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)
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).
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis D Infection
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: lonafarnib/ritonavir - I
    lonafarnib 100 mg BID + ritonavir 100 mg QD;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
  • Experimental: lonafarnib/ritonavir - II
    lonafarnib 150 mg QD + ritonavir 100 mg QD;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
  • Experimental: lonafarnib/ritonavir - III
    lonafarnib 75 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW on Week 12
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
    • Drug: PEG IFN-a
  • Experimental: lonafarnib/ritonavir - IV
    lonafarnib 50 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW on Week 12
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
    • Drug: PEG IFN-a
  • Experimental: lonafarnib/ritonavir - V
    lonafarnib 100 mg BID + ritonavir 50 mg BID;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
  • Experimental: lonafarnib/ritonavir - VI
    lonafarnib 100 mg QD + ritonavir 100 mg QD;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
  • Experimental: lonafarnib/ritonavir - VII
    lonafarnib 50 mg BID + ritonavir 100 mg BID; + PEG IFN-a 180 ug QW;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
    • Drug: PEG IFN-a
  • Experimental: lonafarnib/ritonavir/PEG IFN-a - VIII
    lonafarnib 25 mg BID + ritonavir 100 mg BID + PEG IFN-a 180 ug QW;
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
    • Drug: PEG IFN-a
  • Experimental: lonafarnib/ritonavir/PEG IFN-a - IX
    lonafarnib 50 mg BID + ritonavir 100 mg BID
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
  • Experimental: lonafarnib/ritonavir - X
    lonafarnib 25 mg BID + ritonavir 100 mg BID
    Interventions:
    • Drug: lonafarnib
    • Drug: Ritonavir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 27, 2017)
58
Original Estimated Enrollment  ICMJE
 (submitted: April 25, 2015)
40
Actual Study Completion Date  ICMJE June 15, 2017
Actual Primary Completion Date April 18, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Turkey
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02430194
Other Study ID Numbers  ICMJE EIG-300-Amendment 3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eiger BioPharmaceuticals
Study Sponsor  ICMJE Eiger BioPharmaceuticals
Collaborators  ICMJE Ankara University
Investigators  ICMJE
Principal Investigator: Cihan Yurdaydin, MD Ankara University
PRS Account Eiger BioPharmaceuticals
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP