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
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis B Infection
Drug: Tenofovir DF
Drug: Placebo to match TDF
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 participants with serum HBV DNA < 400 copies/mL at week 72 [ Time Frame: Week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

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
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.
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®
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.
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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, Colorado
University of Colorado School of Medicine Recruiting
Aurora, Colorado, United States, 80045
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 Withdrawn
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
Medanta -The Medicity Recruiting
Gurgaon, Haryana, India, 122 001
Colors Children Hospital Recruiting
Nagpur, Maharashtra, India, 440012
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 Withdrawn
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 Withdrawn
Myslowice, Poland, 41-400
Romania
National Institute of Infectious Diseases Withdrawn
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 Withdrawn
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, 2012-000586-20
Study First Received: July 25, 2012
Last Updated: July 16, 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
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
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 July 22, 2014