Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: TAF

Study type: Interventional

Funder types: Industry

Identifiers

NCT03180619

2016-004625-16 (EudraCT Number)

GS-US-320-4035

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and tolerability and virologic response of tenofovir alafenamide (TAF) in virologically suppressed chronic hepatitis B participants with renal and/or hepatic impairment.

Enrollment: 124 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

All Participants (Parts A and B):

• Adult male or non-pregnant female individuals
• Documented evidence of chronic HBV infection
• Alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN)

Part A Only (renal impairment):

• Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV deoxyribonucleic acid [DNA] < lower limit of quantitation [LLOQ]) for ≥ 6 months prior to screening

  • All individuals must have HBV DNA < 20 International units per milliliter (IU/mL) at screening by central laboratory
  • Both Hepatitis B e-Antigen (HBeAg) positive and negative individuals are eligible to participate

• Moderate renal impairment (30 milliliters per minute [mL/min] ≤ estimated glomerular filtration rate by the cockcroft-gault formula [eGFRcg] ≤ 59 mL/min), severe renal impairment (15 mL/min ≤ eGFRcg < 30 mL/min) or end stage renal disease (ESRD) (eGFR < 15 mL/min) maintained on hemodialysis (HD)

• Stable renal function (for participants with moderate or severe impairment): serum creatinine measured at least once within three months prior to screening. The measurement difference between the value measured within three months prior to screening versus the screening value must be ≤ 25% of the screening value

Part B Only (hepatic impairment):

• Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for ≥ 6 months prior to screening

  • All individuals must have HBV DNA < 20 IU/mL at screening by central laboratory
  • Both HBeAg positive and negative individuals are eligible to participate

• Child-pugh-turcotte (CPT) score of 7-12 (inclusive) OR a past history of CPT score ≥ 7 and any CPT score ≤ 12 at screening

• eGFRCG ≥ 30 mL/min using the Cockcroft-Gault equation

Key Exclusion Criteria:

All Individuals (Parts A & B):

• Women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
• Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study
• Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
• Prior Interferon (IFN) use within 6 months of screening
• Evidence of hepatocellular carcinoma
• Received solid organ or bone marrow transplant
• Significant cardiovascular, pulmonary, or neurological disease
• Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Individuals under evaluation for possible malignancy are not eligible
• Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
• Known hypersensitivity to study drugs, metabolites, or formulation excipients
• Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.

Part A Only (Renal Impairment):

• Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)

• Abnormal hematological and biochemical parameters, including:

  • Hemoglobin < 9 grams per deciliter (g/dL)
  • Absolute neutrophil count < 750/cubic millimeter (mm^3)
  • Platelets ≤ 50,000/mm^3
  • Aspartate aminotransferase (AST) > 10 × ULN
  • Albumin < 3.0 g/dL
  • Total bilirubin > 2.5 × ULN
  • International normalized ratio of prothrombin time (INR) > 1.5 × ULN (unless stable on anticoagulant regimen)

• Individuals with ESRD (i.e. eGFRcg < 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis)

Part B Only (Hepatic Impairment):

• Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt [TIPS])

• History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of screening

• Grade 2 hepatic encephalopathy at screening

• Model for end-stage liver disease (MELD) score ≥ 30

• Abnormal hematological and biochemical parameters, including

  • Absolute neutrophil count < 750/mm^3
  • Platelets < 30,000/mm^3
  • Hemoglobin < 8.0 g/dL

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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124 participants in 3 patient groups

Part A (Renal Impairment): Moderate or Severe Renal Impairment

Experimental group

Description:

Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks.

Treatment:

Drug: TAF

Part A (Renal Impairment): End Stage Renal Disease

Experimental group

Description:

Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks.

Treatment:

Drug: TAF

Part B: Hepatic Impairment

Experimental group

Description:

Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks.

Treatment:

Drug: TAF