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

This study is currently recruiting participants.
Verified March 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01651403
First received: July 25, 2012
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

This placebo-controlled study evaluates the efficacy, safety and tolerability of tenofovir disoproxil fumarate (TDF) in patients 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.


Condition Intervention Phase
Chronic Hepatitis B Infection
Drug: Tenofovir DF
Drug: Tenofovir DF Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of patients with serum HBV DNA < 400 copies/mL at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients 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 ]
  • 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


Estimated Enrollment: 100
Study Start Date: September 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir DF
Tenofovir disoproxil fumarate oral tablet / oral powder
Drug: Tenofovir DF

Tenofovir disoproxil fumarate (tenofovir DF; TDF) oral tablet / oral powder

• Subjects ≥ 17 kg: one tablet once daily (150, 200, 250 or 300 mg tablets based on body weight) or oral powder if unable to swallow a tablet.

Other Name: Viread®
Placebo Comparator: Tenofovir DF Placebo Drug: Tenofovir DF Placebo

Matching placebo oral tablet / oral powder

  • Subjects ≥ 17 kg: one tablet once daily (matching of physical appearance as the corresponding active tablet) or matching oral placebo powder
  • Subjects < 17 kg and subjects ≥ 17 kg who are unable to swallow a tablet will receive once daily matching oral placebo powder

  Eligibility

Ages Eligible for Study:   2 Years to 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01651403

Contacts
Contact: Yvonne Walker yvonne.walker@gilead.com

Locations
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
United States, New York
New York School of Medicine Recruiting
New York, New York, United States, 10016
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Bulgaria
Dr. Georgi Stranski Multiprofile Hospital for Active Treatment Recruiting
Pleven, Bulgaria, 5800
University Multiprofile Hospital for Active Treatment "Sveti Georgi" Recruiting
Plodiv, Bulgaria, 4002
Multiprofile Hospital for Active Treatment "Tokuda Hospital" Recruiting
Sofia, Bulgaria, 1407
India
Gandhi Hospital and Medical College Active, not recruiting
Secunderabad, Andhra Pradesh, India, 500-033
King George Hospital Active, not recruiting
Visakhapatnam, Andhra Prasad, India, 530 002
Nirmal Hospital Private Limited Recruiting
Gujarat, India, 395 002
Korea, Republic of
Kyungpook National University Recruiting
Daegu, Korea, Republic of, 700-721
Gachon University Gil Hospital, Department of Pediatrics Recruiting
Incheon, Korea, Republic of, 405-760
Severance Children's Hospital Recruiting
Seoul, Korea, Republic of, 120-752
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 138-736
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 135-710
Pusan National University Yangsan Hospital Recruiting
Yangsan-si, Korea, Republic of, 626 770
Poland
ID Clinic Recruiting
Myslowice, Poland, 41-400
Romania
National Institute of Infectious Diseases Recruiting
Bucharest, Romania, 021105
Fundeni Clinical Institute - Constantinesco Recruiting
Bucharest, Romania, 022328
Grigore Alexandrescu Emergency Clinical Hospital for Children Recruiting
Bucharest, Romania, 011743
Clinical Infectious Diseases Hospital of Constanta Recruiting
Constanta, Romania, 900708
"Victor Babes" Clinical Hospital of Infectious Diseases and Pneumophtisology Recruiting
Craiova, Romania, 200515
Taiwan
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan, 11217
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Bittoo Kanwar, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01651403     History of Changes
Other Study ID Numbers: GS-US-174-0144
Study First Received: July 25, 2012
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Bulgarian Drug Agency
India: Drugs Controller General of India
Poland: The Central Register of Clinical Trials
Romania: National Agency for Medicines and Medical Devices
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan : Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis
Hepatitis B
HBV

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 17, 2014