A Study to Compare Efficacy and Safety of Tenofovir Used Alone or in Combination With Pegylated Interferon Alpha-2b in Participants With Chronic Hepatitis B and Elevated Alanine Aminotransferase (MK-4031-384)

NCT01727271 | Withdrawn Phase 4

• 1 other identifier: 4031-384
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will compare monotherapy with tenofovir to sequential therapy with pegylated interferon alpha-2b (pegIFN-2b) followed by tenofovir, and to combination therapy with pegIFN-2b + tenofovir, in participants with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and elevated alanine aminotransferase (ALT). All enrolled participants will be be administered tenofovir alone for 8 weeks and then will be randomly assigned to 1 of the 3 treatment arms.

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (3)

• Number of participants who responded to treatment

  Week 128

• Number of participants experiencing adverse events (AEs)

  Up to 128 weeks

• Number of participants discontinuing study therapy due to AEs

  Up to 104 weeks

Study Arms (3)

Tenofovir Monotherapy

ACTIVE COMPARATOR

Tenofovir 300 mg tablet, orally (PO) once daily for 8 weeks, then Tenofovir 300 mg tablet, PO, once daily for an additional 96 weeks (total treatment duration 104 weeks)

Drug: Tenofovir

PegIFN-2b/Tenofovir Sequential Therapy

EXPERIMENTAL

Tenofovir 300 mg tablet, PO, once daily for 8 weeks, then PegIFN-2b, 1.5 mcg/kg subcutaneously (SC), once weekly, for 24 weeks, then Tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)

Drug: Tenofovir; Biological: Pegylated interferon alpha-2b

Peg-IFN-2b + Tenofovir Combination Therapy

EXPERIMENTAL

Tenofovir 300 mg tablet, PO once daily for 8 weeks, then pegIFN-2b, 1.5 mcg/kg SC once weekly and tenofovir 300 mg tablet, PO, once daily for 24 weeks, and then tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)

Drug: Tenofovir; Biological: Pegylated interferon alpha-2b

Interventions

Tenofovir DRUG

Also known as: Truvada

Peg-IFN-2b + Tenofovir Combination Therapy; PegIFN-2b/Tenofovir Sequential Therapy; Tenofovir Monotherapy

Pegylated interferon alpha-2b BIOLOGICAL

Also known as: SCH 054031, MK-4031

Peg-IFN-2b + Tenofovir Combination Therapy; PegIFN-2b/Tenofovir Sequential Therapy

Eligibility Criteria

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

You may qualify if:

• Chronic hepatitis B (hepatitis B surface antigen \[HBsAg\]-positive for \>6 months or evidence of chronic hepatitis B in liver biopsy)
• Elevated serum ALT level
• Liver biopsy or a non-invasive investigation within 12 months prior to randomization with Chronic Hepatitis B
• Treatment naïve or history of interferon for not more than 1 month, taken at least 6 months before enrollment
• Compensated liver disease

You may not qualify if:

• Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component of the study products
• Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
• Need for prolonged or frequent use of systemic acyclovir or famciclovir
• Previously received lamivudine or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog and were resistant to these drugs
• History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices unless banded or other clinical signs of hepatic decompensation
• History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
• Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole, ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g. frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and foscarnet)
• One or more additional known primary or secondary causes of liver disease, other than hepatitis B
• History of clinical pancreatitis
• Pregnant or breastfeeding
• Female participants of childbearing potential and male participants must be willing to use acceptable method of birth control.
• Medical condition that requires frequent or prolonged use of systemic corticosteroids
• Use of warfarin or other anticoagulants during 30 days prior to screening or if expected to be needed during the study period

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis B

Interventions

Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2012
• First Posted: November 15, 2012
• Study Start: August 1, 2013
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: September 19, 2013

Record last verified: 2013-09