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Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Participants With Chronic Hepatitis B Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01651403
Recruitment Status : Active, not recruiting
First Posted : July 27, 2012
Results First Posted : September 19, 2018
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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Brief Summary:
The primary objective of this study is to evaluate the antiviral efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) versus placebo in pediatric population (aged 2 to < 12 years at the time of enrollment) with chronic hepatitis B (CHB) infection.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Infection Drug: Tenofovir DF Drug: TDF Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Patients With Chronic Hepatitis B Infection
Actual Study Start Date : December 6, 2012
Actual Primary Completion Date : August 7, 2017
Estimated Study Completion Date : November 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Tenofovir DF (Blinded Randomized Treatment)
Participants will receive tenofovir disoproxil fumarate (tenofovir DF; TDF) for 48 weeks.
 Drug: Tenofovir DF
  • Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).
  • Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.
Other Name: Viread®
Placebo Comparator: Placebo to match TDF (Blinded Randomized Treatment)
Participants will receive TDF placebo for 48 weeks.
 Drug: TDF Placebo
  • Participants weighing ≥ 17 kg will receive TDF placebo tablet administered orally once daily.
  • Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF placebo oral powder once daily.
Experimental: Tenofovir DF (Open-label Treatment)
Following 72 weeks (protocol amendment 2) or 48 weeks (protocol amendment 3) of blinded randomized treatment, participants will switch to open-label TDF treatment for an additional 120 weeks (protocol amendment 2) or 144 weeks (protocol amendment 3).
 Drug: Tenofovir DF
  • Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).
  • Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.
Other Name: Viread®
Experimental: Tenofovir DF (Open-label Extension Phase)
Following the completion of study at Week 192, participants may have the option to receive open-label TDF until it is commercially available in that country for treatment of chronic HBV in patients of their age and weight.
 Drug: Tenofovir DF
  • Participants weighing ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).
  • Participants weighing < 17 kg or ≥ 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.
Other Name: Viread®


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 [ Time Frame: Week 48 ]

Secondary Outcome Measures :
  1. Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 [ Time Frame: Week 48 ]
    HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.

  2. Percentage of Participants With Normal ALT at Week 48 [ Time Frame: Week 48 ]
    Normal alanine amino transferase (ALT) was defined as ≤ 30 U/L for males and females 0-12 years based on the American Association for the Study of Liver Diseases (AASLD) pediatric normal range.

  3. Percentage of Participants With Normalized ALT at Week 48 [ Time Frame: Week 48 ]
    Normal alanine amino transferase (ALT) was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.

  4. Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT at Week 48 [ Time Frame: Week 48 ]
    Normal alanine amino transferase (ALT) was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.

  5. Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48 [ Time Frame: Week 48 ]
  6. Percentage of Participants With HBsAg Loss [ Time Frame: Week 48 ]
    HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.

  7. Percentage of Participants With HBsAg Seroconversion [ Time Frame: Week 48 ]
    HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.

  8. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 48 [ Time Frame: Baseline; Week 48 ]
  9. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 96 [ Time Frame: Baseline; Week 96 ]
  10. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 144 [ Time Frame: Baseline; Week 144 ]
  11. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 192 [ Time Frame: Baseline; Week 192 ]
  12. Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density [ Time Frame: Baseline; Week 48 ]
  13. Percent Change From Baseline in Bone Mineral Density of Spine [ Time Frame: Baseline; Week 48 ]

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 11 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Male or Female, 2 to < 12 years of age
  • Weight ≥ 10 kg
  • Chronic HBV infection ≥ 6 months
  • HBeAg-positive or HBeAg-negative
  • HBV Viral Load ≥ 100,000 copies/mL
  • Alanine aminotransferase (ALT) ≥ 1.5 x the upper limit of the normal range (ULN) at screening
  • Creatinine Clearance ≥ 80 mL/min/1.73m^2
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3, hemoglobin ≥ 10 g/dL
  • Negative pregnancy test at screening
  • No prior tenofovir DF therapy (participants may have received prior interferon-alfa and/or other oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon-alfa therapy ≥ 6 months prior to screening; participants experienced on other anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm)

Key Exclusion Criteria:

  • Pregnant or lactating
  • Decompensated liver disease
  • Received interferon therapy within 6 months of screening
  • Received anti-HBV nucleoside/nucleotide therapy within 16 weeks of screening
  • Alpha-fetoprotein levels > 50 ng/mL
  • Evidence of hepatocellular carcinoma (HCC)
  • Co-infection with HIV, acute hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
  • Chronic liver disease not due to HBV
  • History of significant renal, cardiovascular, pulmonary, neurological or bone disease
  • Long term non-steroidal, anti-inflammatory drug therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations
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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): NCT01651403


Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol: Original  [PDF] July 22, 2011
Study Protocol: Amendment 1  [PDF] March 7, 2012
Study Protocol: Amendment 2  [PDF] November 8, 2012
Study Protocol: Amendment 3  [PDF] February 29, 2016
Study Protocol: Amendment 4  [PDF] August 4, 2016
Statistical Analysis Plan  [PDF] January 10, 2018

More Information
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01651403    
Other Study ID Numbers: GS-US-174-0144
2012-000586-20 ( EudraCT Number )
First Posted: July 27, 2012    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: July 1, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Hepatitis
Hepatitis B
HBV
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
 RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents