Boceprevir-based Therapy to Rescue HCV Genotype 1/HBV Infected Patients Refractory to Combination Therapy

NCT02060058 | Completed Phase 3 Results DMC

• 1 other identifier: KMUHIRB-2013-10-03 (I)
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C, Chronic

Keywords

hepatitis C virus; hepatitis B virus; boceprevir; null responder; partial responder; relapser

Outcome Measures

Primary Outcomes (1)

• Number of Full Analysis Set Participants Who Received HCV Anti-viral Therapy With Sustained Virological Response (SVR)

  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)

  week 24

Secondary Outcomes (1)

• Key Secondary Endpoint of This Clinical Trial-SVR in mITT

  week 24

Other Outcomes (1)

• The Other Responses in the mITT Population/Safty- HBV Virologic Response

  week 24

Study Arms (3)

Patients with 32 week therapy

EXPERIMENTAL

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

Patients with 48 weeks therapy

EXPERIMENTAL

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

Null responder or cirrhotic patients

EXPERIMENTAL

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

Interventions

Stop trial intervention for boceprevir, PEG-IFN and RBV DRUG

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.

Also known as: Stop trial intervention for arm A, Stop trial intervention for arm B, Stop trial intervention for arm C

Null responder or cirrhotic patients; Patients with 32 week therapy; Patients with 48 weeks therapy

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patient must be 20 years or older
• \. Patient must have HCV GT1 infection combined with HBV infection.
• \. Patients must be serum HCV RNA detectable, anti-HCV positive, HBsAg positive and HBeAg negative.
• \. Patient has previously failed treatment with PEG-IFN-α 2a or 2b/RBV for minimum of 12 weeks of treatment.
• \. 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.
• \. 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.
• \. Patient is able and willing to provide signed informed consent (prepared by and administered by the physician) as required by local country requirements.

You may not qualify if:

• \. Mixed genotypes including HCV genotype other than genotype 1.
• \. Patient has received boceprevir, narlaprevir, telaprevir, or any other HCV protease inhibitor treatment.
• \. Patient has evidence of decompensated liver disease including but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy.
• \. Patient has an organ transplant other than cornea or hair.
• \. Patient is co-infected with human immunodeficiency virus (HIV)
• \. Patient requires or is anticipated to require any of the following prohibited medications: midazolam, pimozide, amiodarone, flecainide, propafenone, quinidine, and ergot derivatives
• \. Patient with clinical diagnosis or evidence of substance abuse involving alcohol, intravenous drugs, inhalational psychotropics, narcotics, cocaine prescription or over-the-counter drugs.
• \. 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.
• \. 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.
• \. Major hemoglobinopathy (e.g., thalassemia major), coagulopathy or any other cause of or tendency to hemolysis or bleeding

Sponsors & Collaborators

• Kaohsiung Medical University Chung-Ho Memorial Hospital: lead
• National Taiwan University Hospital: collaborator

Study Sites (1)

Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

Kaohsiung City, 80787, Taiwan

Location

Related Publications (16)

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Related Links

• Approval of Victrelis (boceprevir) a direct acting antiviral drug (DAA) to treat hepatitis C virus (HCV). 2011

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C; Hepatitis B

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepadnaviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The limitation of this study is the limited case number.

Results Point of Contact

• Title: Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine
• Organization: Kaohsiung Medical University Hospital

hsmonyan@gmail.com

+886-7-3121101

Study Officials

• Ming-Lung Yu, Professsor

  Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: February 11, 2014
• Study Start: November 1, 2013
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2016-05

Locations

TW (1)