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Boceprevir-based Therapy to Rescue HCV Genotype 1/HBV Infected Patients Refractory to Combination Therapy (BOLERO-CB)

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ClinicalTrials.gov Identifier: NCT02060058
Recruitment Status : Completed
First Posted : February 11, 2014
Results First Posted : March 13, 2018
Last Update Posted : March 13, 2018
Sponsor:
Collaborator:
National Taiwan University Hospital
Information provided by (Responsible Party):
Kaohsiung Medical University Chung-Ho Memorial Hospital

Brief Summary:
The aim of this study is to explore the efficacy and safety of boceprevir -based triple therapy to rescue HCV genotype 1 (HCV GT1)/HBV dually infected patients refractory to previous peginterferon (PEG-IFN) plus ribavirin (RBV) combination therapy.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: Stop trial intervention for boceprevir, PEG-IFN and RBV Phase 3

Detailed Description:

Liver disease, especially viral hepatitis, is an important public health issue, which frequent leads to liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related death. Around 340 to 400 million persons are infected with hepatitis B virus (HBV) and 130 to 210 million persons are infected with hepatitis C virus (HCV) worldwide, In Taiwan, the prevalence of HBV infection is 15-20%, and the prevalence of HCV infection is 2-5% in general population. Moreover, there are some HCV-hyperendemic areas in southern Taiwan with anti-HCV prevalence rate of as high as 30-40%.

HBV/HCV dual infections is not uncommon in HBV epidemic areas, such as Southeastern Asia, with a prevalence rate of 1.1% in southern Taiwan. Recent study showed that the risk of HCC incidence is even higher among HBV/HCV co-infected persons than those with HBV or HCV mono-infection, indicating the importance of disease control in this clinical setting.

The PEG-IFN/RBV has been effective in the treatment of HCV-dominant, treatment-naïve patients with HCV/HBV dual infections. For treatment-naive HCV genotype 1 (HCV GT1)/HBV co-infected patients, 48 weeks of peginterferon (PEG-IFN) plus ribavirin (RBV) could achieve an HCV sustained virological response (SVR) rate of 72%, which was comparable to 77% for patients with HCV GT1 monoinfection. For treatment-naive HCV GT2 or GT3 /HBV co-infected patients, 24 weeks of PEG-IFN plus RBV could achieve an HCV SVR rate of 83%, which was comparable to 84% for patients with HCV GT2/3 monoinfection . Furthermore, PEG-IFN plus RBV combination therapy could enhance seroclearance of hepatitis B surface antigen (HBsAg) with an HBsAg loss rate of upto 11%. Nevertheless, there is about 30% of HCV GT1/HBV and 20% of HCV GT2 or 3/HBV co-infected patients refractory to current PEG-IFN/RBV combination therapy, which remains at high risk of HCC and liver-related death.

Boceprevir is an oral antiviral drug, which is NS3/4A protease inhibitor. Boceprevir has been approved for treating HCV GT1 infection by Food and Drug Administration (FDA) on 11 May 2011. For HCV GT1 mono-infected patients who refractory to previous PEG-IFN plus RBV combination therapy, becoprevir combined with PEG-IFN/RBV triple therapy can improve the treatment efficacy. The SVR rate of becoprevir-based triple therapy is about 3 times when compared to patients who received PEG-IFN with RBV dual therapy [14].The investigators , therefore, hypothesize that boceprevir plus PEG-IFN/RBV is effective in treating HCV GT1/HBV dually infected patients who are refractory to previous PEG-IFN/RBV combination therapy.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Boceprevir-based Triple Therapy to Rescue HCV Genotype 1/HBV Dually Infected Patients Refractory to Peginterferon Plus Ribavirin Combination Therapy
Study Start Date : November 2013
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hepatitis
Drug Information available for: Boceprevir

Arm Intervention/treatment
Experimental: Patients with 32 week therapy

For non-cirrhotic patients whose response of previous HCV therapy with PEG-IFN/RBV were relapse or partial response, PEG-IFN/RBV lead-in therapy is performed during 0-4 weeks, then add boceprevir from week 5 (boceprevir+ PEG-IFN/RBV). If HCV RNA is undetectable during 8-24 weeks, boceprevir+PEG-IFN/RBV triple therapy will be administered from week 5 to week 32.

Dosage of drugs: Boceprevir 800mg tid po, PegIntron 1.5 mcg/kg im QW, and Ribavirin 800 to 1400 mg/day PO divided BID Regimen adjusted according to body weight.

Stop trial intervention for patients with 32 week therapy: for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped (Stop trial intervention for boceprevir, PEG-IFN and RBV for arm A).

Drug: Stop trial intervention for boceprevir, PEG-IFN and RBV

Stop trial intervention for patients with 32 week therapy (arm A): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for patients with 48 weeks therapy (arm B): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for for null responder or cirrhotic patients: (arm C) for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Other Names:
  • Stop trial intervention for arm A
  • Stop trial intervention for arm B
  • Stop trial intervention for arm C

Experimental: Patients with 48 weeks therapy

For non-cirrhotic patients whose response of previous HCV therapy with PEG-IFN/RBV were relapse or partial response, PEG-IFN/RBV lead-in therapy is performed during 0-4 weeks, then add boceprevir from week 5 (boceprevir+ PEG-IFN/RBV). If HCV RNA is detectable at week 8 and undetectable at week 24, boceprevir+ PEG-IFN/RBV triple therapy will be administered from week 5 to week 32, followed by additional 12 weeks of PEG-IFN/RBV therapy.

Dosage of drugs: as Patients with 32 week therapy Stop trial intervention for patients with 48 weeks therapy: for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped (Stop trial intervention for boceprevir, PEG-IFN and RBV for arm B).

Drug: Stop trial intervention for boceprevir, PEG-IFN and RBV

Stop trial intervention for patients with 32 week therapy (arm A): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for patients with 48 weeks therapy (arm B): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for for null responder or cirrhotic patients: (arm C) for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Other Names:
  • Stop trial intervention for arm A
  • Stop trial intervention for arm B
  • Stop trial intervention for arm C

Experimental: Null responder or cirrhotic patients

For null responder or cirrhotic patients, PEG-IFN/RBV lead-in therapy is performed during 0-4 weeks, then add boceprevir from week 5 to 48.

Dosage of drugs: as Patients with 32 week therapy Stop trial intervention for for null responder or cirrhotic patients: for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped (Stop trial intervention for boceprevir, PEG-IFN and RBV for arm C).

Drug: Stop trial intervention for boceprevir, PEG-IFN and RBV

Stop trial intervention for patients with 32 week therapy (arm A): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for patients with 48 weeks therapy (arm B): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Stop trial intervention for for null responder or cirrhotic patients: (arm C) for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.

Other Names:
  • Stop trial intervention for arm A
  • Stop trial intervention for arm B
  • Stop trial intervention for arm C




Primary Outcome Measures :
  1. Number of Full Analysis Set Participants Who Received HCV Anti-viral Therapy With Sustained Virological Response (SVR) [ Time Frame: week 24 ]
    The methods used to assess this outcome measure is by full-analysis set (FAS), which is defined as undetectable HCV-RNA at follow-up Week 24 in subjects receiving ≥1 dose of any antiviral medication (Boceprevir/peginterferon/ribavirin)


Secondary Outcome Measures :
  1. Key Secondary Endpoint of This Clinical Trial-SVR in mITT [ Time Frame: week 24 ]
    The total 7 patients had SVR by mITT in this clincial-trial, which is defined as undetectable HCV-RNA at follow-up Week 24 in subjects receiving ≥1 dose of Boceprevir


Other Outcome Measures:
  1. The Other Responses in the mITT Population/Safty- HBV Virologic Response [ Time Frame: week 24 ]
    HBV virologic response, defined as serum HBV DNA levels to < 200 IU/mL at follow-up week 24 among patients with detectable HBV DNA at baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Patient must be 20 years or older
  • 2. Patient must have HCV GT1 infection combined with HBV infection.
  • 3. Patients must be serum HCV RNA detectable, anti-HCV positive, HBsAg positive and HBeAg negative.
  • 4. Patient has previously failed treatment with PEG-IFN-α 2a or 2b/RBV for minimum of 12 weeks of treatment.
  • 5. Patient must have compensated liver disease consistent with CHC and/or CHB, and no other etiology. Note: patients with cirrhosis should have a liver imaging study (e.g. ultrasound, CT scan or MRI) within the preceding 6 months showing no evidence of hepatocellular carcinoma.
  • 6. Patient meets all of the requirements and none of the contra-indications for treatment with PEG-IFN alpha-2b/RBV or boceprevir defined in the labels for the PEG-IFN/RBV to be used in combination with boceprevir.
  • 7. Patient is able and willing to provide signed informed consent (prepared by and administered by the physician) as required by local country requirements.

Exclusion Criteria:

  • 1. Mixed genotypes including HCV genotype other than genotype 1.
  • 2. Patient has received boceprevir, narlaprevir, telaprevir, or any other HCV protease inhibitor treatment.
  • 3. Patient has evidence of decompensated liver disease including but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
  • 4. Patient meets any of the following exclusionary hematologic and biochemical criteria (documentation required) Hemoglobin <12 gm/dL for females and <13 gm/dL for males Neutrophils <1500/mm3 Platelets <100,000/mm3
  • 5. Patient has an organ transplant other than cornea or hair.
  • 6. Patient is co-infected with human immunodeficiency virus (HIV)
  • 7. Patient requires or is anticipated to require any of the following prohibited medications: midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives
  • 8. Patient with clinical diagnosis or evidence of substance abuse involving alcohol, intravenous drugs, inhalational psychotropics, narcotics, cocaine prescription or over-the-counter drugs.
  • 9. Patient previously demonstrated clinically significant hypersensitivity or other contraindication to any component of the boceprevir formulation. This drug contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
  • 10. Serious illness, including malignancy, active coronary artery disease or cardiac dysfunction within 24 weeks prior to study entry, that in the opinion of the site investigator may preclude completion of the treatment regimen.
  • 11. Major hemoglobinopathy (e.g., thalassemia major), coagulopathy or any other cause of or tendency to hemolysis or bleeding

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): NCT02060058


Locations
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Taiwan
Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Kaohsiung, Taiwan, 80787
Sponsors and Collaborators
Kaohsiung Medical University Chung-Ho Memorial Hospital
National Taiwan University Hospital
Investigators
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Study Chair: Ming-Lung Yu, Professsor Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Additional Information:
Publications:

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Responsible Party: Kaohsiung Medical University Chung-Ho Memorial Hospital
ClinicalTrials.gov Identifier: NCT02060058     History of Changes
Other Study ID Numbers: KMUHIRB-2013-10-03 (I)
First Posted: February 11, 2014    Key Record Dates
Results First Posted: March 13, 2018
Last Update Posted: March 13, 2018
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Until now if sharing data is not decided

Keywords provided by Kaohsiung Medical University Chung-Ho Memorial Hospital:
hepatitis C virus
hepatitis B virus
boceprevir
null responder
partial responder
relapser

Additional relevant MeSH terms:
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Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ribavirin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents