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Trial record 77 of 339 for:    hepatitis b | Recruiting, Not yet recruiting, Available Studies

Tenofovir Alafenamide (TAF) in Children and Adolescents With Chronic Hepatitis B Virus Infection

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ClinicalTrials.gov Identifier: NCT02932150
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : June 14, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

The primary objective of Cohort 1 of this study is to evaluate the safety, tolerability, and antiviral activity (HBV DNA < 20 IU/mL) of tenofovir alafenamide (TAF) 25 mg once daily versus placebo through Week 24 in treatment-naive and treatment-experienced adolescent adolescents (aged 12 to < 18 years) with chronic hepatitis B (CHB).

Cohort 2 will consist of 2 parts: Part A and Part B. Intensive pharmacokinetic (PK) data will be collected from all participants in Part A to confirm the dose of TAF in each dose group and the remaining participants will be enrolled into Part B once dose confirmation is achieved. The primary objectives of Part A are to evaluate the steady-state PK of TAF and tenofovir (TFV) and confirm the dose of TAF given once daily in children (aged 2 to < 12 years) with CHB. The primary objective of Part B is to evaluate the safety and tolerability of TAF at Week 48 and the antiviral activity (HBV DNA < 20 IU/mL) of TAF at Week 24 in children (aged 2 to < 12 years) with CHB.


Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: TAF Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Evaluation of the Pharmacokinetics, Safety, and Antiviral Efficacy of Tenofovir Alafenamide (TAF) in Children and Adolescent Subjects With Chronic Hepatitis B Virus Infection
Actual Study Start Date : November 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Tenofovir

Arm Intervention/treatment
Experimental: TAF (Cohort 1)
Participants (12 to < 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks
Drug: TAF
Administered orally once daily

Placebo Comparator: Placebo (Cohort 1)
Participants (12 to < 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks
Drug: Placebo
Administered orally once daily

Experimental: TAF (Cohort 2 Group 1)
Participants (6 to < 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks
Drug: TAF
Administered orally once daily

Experimental: TAF (Cohort 2 Group 2)
Participants (6 to < 12 years) weighing 17 kg to < 25 kg will receive TAF 15 mg tablet for 24 weeks
Drug: TAF
Administered orally once daily

Experimental: TAF (Cohort 2 Group 3)
Participants (2 to < 6 years) weighing < 17 kg who are unable to swallow a tablet will receive oral granules of TAF (dose to be determined) for 24 weeks.
Drug: TAF
Administered orally once daily

Experimental: TAF (Cohort 2 Placebo)
Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.
Drug: Placebo
Administered orally once daily

Experimental: Open-Label TAF
Following 24 weeks of blinded randomized treatment, participants will be eligible to participate in an open-label extension phase to receive TAF for an additional 216 weeks.
Drug: TAF
Administered orally once daily




Primary Outcome Measures :
  1. Incidence of treatment-emergent serious adverse events (SAEs) and treatment-emergent adverse events at Week 24 (Cohort 1) [ Time Frame: Week 24 ]
  2. Incidence of treatment-emergent SAEs and treatment-emergent adverse events in participants treated with TAF or placebo for 24 weeks followed by 24 weeks of open-label TAF at Week 48 (Cohort 2) [ Time Frame: Week 48 ]
  3. Percentage of participants with plasma HBV DNA < 20 IU/mL at Week 24 [ Time Frame: Week 24 ]
  4. PK Parameter: AUCtau of TAF for participants from Cohort 2 Part A [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).


Secondary Outcome Measures :
  1. Percentage of participants experiencing graded laboratory abnormalities [ Time Frame: Weeks 24, 48, 96, and 240 ]
  2. Development as measured by Tanner Stage Assessment [ Time Frame: Weeks 24, 48, 96, and 240 ]
  3. Percentage change from baseline in bone mineral density (BMD) of whole body (minus head) by dual imaging x-ray absorptiometry (DXA) [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  4. Percentage change from baseline in BMD of lumbar spine by DXA [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  5. Change from baseline in serum creatinine [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  6. Change from baseline in estimated glomerular filtration rate (eGFR) by the Schwartz formula [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  7. Incidence of treatment-emergent SAEs and treatment-emergent adverse events at Week 24 (Cohort 2) [ Time Frame: Week 24 ]
  8. Incidence of treatment-emergent SAEs and treatment-emergent adverse events in participants treated with TAF or placebo for 24 weeks followed by open-label TAF at Week 48 (Cohort 1) and Weeks 96 and 240 (Cohorts 1 and 2) [ Time Frame: Week 48 (Cohort 1) and Week 96 and 240 (Cohort 1 and 2) ]
  9. Change from baseline in retinol-binding protein at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  10. Change from baseline in beta-2-microglobulin at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  11. Change from baseline in glucose at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  12. Percentage change from baseline in glucose at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  13. Change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  14. Percentage change from baseline in phosphate at Weeks 4, 8, 12, 24, and 48 [ Time Frame: Baseline; Weeks 4, 8, 12, 24, and 48 ]
  15. Percentage of participants with plasma HBV DNA < 20 IU/mL at Weeks 48, 96, and 240 [ Time Frame: Weeks 48, 96, and 240 ]
  16. Proportion of participants with plasma HBV DNA < 20 IU/mL (target not detected) at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  17. Percentage of participants with alanine aminotransferase (ALT) normalization at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  18. Composite endpoint of percentage of participants with ALT normalization and HBV DNA < 20 IU/mL at Weeks 24, 48, 96 and 240 [ Time Frame: Weeks 24, 48, 96 and 240 ]
  19. Change from baseline in fibrosis as assessed by FibroTest at Weeks 24, 48, 96, and 240 [ Time Frame: Baseline; Weeks 24, 48, 96, and 240 ]
  20. Percentage of participants with hepatitis B e antigen (HBeAg) loss at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  21. Percentage of participants with HBeAg seroconversion to anti-HBe at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only) [ Time Frame: Weeks 24, 48, 96, and 240 ]
  22. Percentage of participants with composite endpoint of HBeAg seroconversion and HBV DNA < 20 IU/mL at Weeks 24, 48, 96, and 240 (in HBeAg-positive participants only) [ Time Frame: Weeks 24, 48, 96, and 240 ]
  23. Percentage of participants with hepatitis B surface antigen (HBsAg) loss at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  24. Percentage of participants with HBsAg seroconversion to anti-HBs at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  25. Incidence of resistance mutations at Weeks 24, 48, 96, and 240 [ Time Frame: Weeks 24, 48, 96, and 240 ]
  26. Acceptability of study drug [ Time Frame: Baseline; Weeks 4, 24, and 36 ]
    To assess acceptability of study drug, the investigator will ask participants on a scale of 1-7 how much they like the taste of the medication (1 = dislike very much to 7 = like very much).

  27. Palatability of study drug [ Time Frame: Baseline; Weeks 4, 24, and 36 ]
    To assess palatability of study drug, the investigator will ask participants on a scale of 0-3 how easy it was to swallow the pill (0 = poor to 3 = excellent).

  28. PK Parameter: AUCtau of TAF (Cohort 1 only) and tenofovir (TFV) for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  29. PK Parameter: AUClast of TAF and TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  30. PK Parameter: Ctau of TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  31. PK Parameter: Cmax of TAF and TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Cmax is defined as the maximum observed concentration of drug.

  32. PK Parameter: Clast of TAF and TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Clast is defined as the last observable concentration of drug.

  33. PK Parameter: Tmax of TAF and TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Tmax is defined as the time of Cmax (the maximum concentration of drug).

  34. PK Parameter: Tlast of TAF and TFV for participants who participate in the optional intensive PK substudy [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Tlast is defined as the time (observed time point) of Clast.

  35. PK Parameter: λz of TAF and TFV for participants who participate in the optional intensive PK substudy (where possible) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.

  36. PK Parameter: CL/F of TAF and TFV for participants who participate in the optional intensive PK substudy (where possible) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    CL/F is defined as the apparent oral clearance following administration of the drug.

  37. PK Parameter: Vz/F of TAF and TFV for participants who participate in the optional intensive PK substudy (where possible) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    Vz/F is defined as the apparent volume of distribution of the drug.

  38. PK Parameter: t1/2 of TAF and TFV for participants who participate in the optional intensive PK substudy (where possible) [ Time Frame: Predose, 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 5, and 8 hours postdose at Week 4 or 8 ]
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion criteria:

  • Males and non-pregnant, non-lactating females
  • Weight at screening as follows:

    • Cohort 1 = ≥ 35 kg (≥ 77 lbs)
    • Cohort 2 Group 1 = ≥ 25 kg (≥ 55 lbs)
    • Cohort 2 Group 2 = ≥ 17 kg to < 25 kg (≥ 37 lbs to <55 lbs)
    • Cohort 2 Group 3 = < 17 kg (< 37 lbs)
  • Willing and able to provide written informed consent/assent (child and parent/legal guardian)
  • Documented evidence of CHB (eg, HBsAg-positive for ≥ 6 months)
  • Treatment-naive or treatment-experienced will be eligible for enrollment.
  • Estimated creatinine clearance (CLCr) ≥ 80 mL/min/1.73m^2 (using the Schwartz formula)
  • Normal ECG

Key Exclusion criteria:

  • Females who are breastfeeding
  • Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study.
  • Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
  • Evidence of hepatocellular carcinoma (Note: if screening alpha-fetoprotein (AFP) is < 50 ng/mL no imaging study is needed; however, if the screening AFP is > 50 ng/mL an imaging study is required)
  • Any history of, or current evidence of, clinical hepatic decompensation
  • Abnormal hematological and biochemical parameters
  • Chronic liver disease of non-HBV etiology (e.g., hemochromatosis, alpha-1 antitrypsin deficiency, cholangitis)
  • Received solid organ or bone marrow transplant
  • Currently receiving therapy with immunomodulators (eg, corticosteroids), or immunosuppressants
  • Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
  • Malignancy within the 5 years prior to screening. Individuals under evaluation for possible malignancy are not eligible.
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance.

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


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): NCT02932150


Contacts
Contact: Gilead Study Team GS-US-320-1092@gilead.com

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Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02932150     History of Changes
Other Study ID Numbers: GS-US-320-1092
2016-000785-37 ( EudraCT Number )
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: June 14, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:
CHB
HBV

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Virus Diseases
Liver Diseases
Digestive System 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