Evaluating the Efficacy, Safety and Tolerability of Tenofovir DF in Pediatric Patients With Chronic Hepatitis B Infection

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01651403
First received: July 25, 2012
Last updated: July 16, 2014
Last verified: July 2014

July 25, 2012
July 16, 2014
September 2012
May 2016   (final data collection date for primary outcome measure)
Proportion of participants with serum HBV DNA < 400 copies/mL at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
Proportion of patients with serum HBV DNA < 400 copies/mL at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01651403 on ClinicalTrials.gov Archive Site
  • Proportion of participants with hepatitis B e antigen (HBeAg) seroconversion at Week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Cumulative Incidence of at least 4% decrease from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
  • Proportion of participants with normal ALT and normalization of ALT [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Composite endpoint of proportion of participants with HBV DNA < 400 copies/mL and normal ALT [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Genotypic changes from baseline within the HBV polymerase for patients who were viremic (HBV DNA > or equal 400 copies/mL) with confirmed virologic breakthrough [ Time Frame: Weeks 72, 144, 192 or Early Discontinuation ] [ Designated as safety issue: No ]
  • Proportion of participants with HBV DNA < 169 copies/mL [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of participants with HBsAg loss and seroconversion [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Proportion of patients with HBeAg seroconversion at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
  • Cumulative Incidence of at least 4% decrease from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in bone mineral density of lumbar spine [ Time Frame: Week 72 ] [ Designated as safety issue: Yes ]
  • Safety and Tolerability of Therapy [ Time Frame: Up to Week 192 ] [ Designated as safety issue: Yes ]
    Safety and tolerability is measured by the frequency of laboratory abnormalities reported as adverse events.
  • Biochemical and serological responses [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    Biochemical and serological responses as measured by normal/normalization of ALT, proportion of subjects with HBV DNA < 400 copies/mL and normal ALT, proportion of subjects with HBV DNA < 169 copies/mL, proportion of subjects with HBsAg loss and seroconversion
  • Viral Resistance [ Time Frame: Weeks 72, 144, 192 or Early Discontinuation ] [ Designated as safety issue: No ]
    Genotypic changes from baseline within the HBV polymerase for patients who were viremic (HBV DNA > or equal 400 copies/mL) with confirmed virologic breakthrough
Not Provided
Not Provided
 
Evaluating the Efficacy, Safety and Tolerability of Tenofovir DF in Pediatric Patients With Chronic Hepatitis B Infection
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

This placebo-controlled study evaluates the efficacy, safety and tolerability of tenofovir disoproxil fumarate (TDF) in participants 2 to < 12 years old with chronic Hepatitis B infection. While studies have shown significant virologic response in adults and adolescents, the effect in children is not well established. This study will provide valuable data that can help establish the efficacy and safety profiles of TDF in children. The study will consist of 72 weeks of blinded randomized treatment, after which participants will switch to open-label TDF treatment for an additional 120 weeks.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Chronic Hepatitis B Infection
  • Drug: Tenofovir DF
    • Participants ≥ 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight).
    • Participants < 17 kg and participants ≥ 17 kg who are unable to swallow a tablet will receive oral powder containing 40 mg of TDF once daily.
    Other Name: Viread®
  • Drug: Placebo to match TDF

    Matching placebo oral tablet / oral powder

    • Participants ≥ 17 kg will receive one tablet of placebo to match TDF administered orally once daily
    • Participants < 17 kg and participants ≥ 17 kg who are unable to swallow a tablet will receive placebo to match TDF oral powder once daily
  • Experimental: Tenofovir DF
    Participants will receive tenofovir disoproxil fumarate (tenofovir DF; TDF) for 72 weeks during the blinded randomized treatment, and will switch to open-label TDF treatment for an additional 120 weeks.
    Intervention: Drug: Tenofovir DF
  • Placebo Comparator: Placebo to match TDF
    Participants will receive placebo to match TDF for 72 weeks during the blinded randomized treatment, and will switch to open-label TDF treatment for an additional 120 weeks.
    Interventions:
    • Drug: Tenofovir DF
    • Drug: Placebo to match TDF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
March 2019
May 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

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

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
Both
2 Years to 11 Years
No
Contact: Yvonne Walker yvonne.walker@gilead.com
United States,   Bulgaria,   India,   Korea, Republic of,   Poland,   Romania,   Taiwan
 
NCT01651403
GS-US-174-0144, 2012-000586-20
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Bittoo Kanwar, MD Gilead Sciences
Gilead Sciences
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP