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)

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Pilot, Randomized, Multi-Center Study to Compare Efficacy and Safety of Tenofovir Monotherapy Alone With Tenofovir Monotherapy Followed by Concurrent Combination of Pegylated Interferon-Alpha-2b and Tenofovir or Tenofovir Monotherapy Followed by Sequential Therapy of Pegylated Interferon-Alpha-2b and Tenofovir in HBeAG-Positive Chronic Hepatitis B Patients With Raised ALT.

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Tenofovir
* Biological: Pegylated interferon alpha-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tenofovir Monotherapy<br>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<br> <br> * Other names: Truvada;|
| Experimental: PegIFN-2b/Tenofovir Sequential Therapy<br>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<br> <br> * Other names: Truvada;Biological: Pegylated interferon alpha-2b<br> <br> * Other names: MK-4031;|
| Experimental: Peg-IFN-2b + Tenofovir Combination Therapy<br>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<br> <br> * Other names: Truvada;Biological: Pegylated interferon alpha-2b<br> <br> * Other names: MK-4031;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |