Hepatitis B
Conditions
Brief summary
The primary objective of this study is to characterize the long term (ie, 96 weeks of follow up) bone safety profile of open-label tenofovir disoproxil fumarate (tenofovir DF) treatment in CHB-infected adolescents. This includes prospectively evaluating and comparing the bone mineral density (BMD) change between CHB-infected adolescents 12 to \< 18 years of age treated with tenofovir DF in European treatment centers who are assigned to one of two schedules for renal and bone laboratory monitoring and BMD measurement.
Interventions
DRUGTenofovir DF
300 mg tablet administered orally once daily for up to 96 weeks
RADIATIONDEXA Scan
Dual energy x-ray absorptiometry (DEXA) scans administered at protocol-specified time points
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. 12 to \<16 years of age 2. Documented chronic hepatitis B virus (HBV) infection 3. Weight ≥ 35 kg 4. Able to swallow oral tablets 5. Negative pregnancy test for females of childbearing potential 6. Adequate kidney (renal) function 7. Parent or legal guardian of potential study subjects able to provide written informed consent Key
Exclusion criteria
1. Previously received tenofovir DF 2. Sexually-active males or females of reproductive potential who are not willing to use an effective method of contraception during the study 3. Females who are pregnant or breastfeeding, or females who wish to become pregnant during the course of the study 4. Known hypersensitivity to tenofovir DF, the metabolites or formulation excipients 5. Any condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with treatment requirements Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Bone-Related Adverse Events and/or a ≥ 4% Reduction in Bone Mineral Density (BMD) From Baseline to Week 96 | Baseline to Week 96 |
Countries
Belgium, France, Greece, Italy, Romania, Spain, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study sites in Europe. The first participant was screened on 03 July 2015. The last study visit occurred on 11 April 2018. The study did not achieve targeted enrollment as it was prematurely terminated by the Pharmacovigilance Risk Assessment Committee (PRAC).
Pre-assignment details
35 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir DF + Increased Bone/Renal Monitoring One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans every 24 weeks from baseline to Week 96 (5 scans), and monitoring of renal function at 4 and 12 weeks after baseline and every 12 weeks thereafter. With the exception of an enhanced monitoring protocol for bone and renal outcomes, participants were managed according to local standards of care. | 15 |
| Tenofovir DF + Prespecified Bone Monitoring One 300 mg tablet given once daily for up to 96 weeks + laboratory bone biomarker testing and lumbar spine and whole-body DXA scans at baseline, Week 48, and Week 96. With the exception of pre-specified bone monitoring, participants were managed according to local standards of care. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 13 | 12 |
Baseline characteristics
| Characteristic | Tenofovir DF + Increased Bone/Renal Monitoring | Tenofovir DF + Prespecified Bone Monitoring | Total |
|---|---|---|---|
| Age, Continuous | 14 years STANDARD_DEVIATION 1.4 | 14 years STANDARD_DEVIATION 1.5 | 14 years STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 12 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 5 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment Belgium | 2 participants | 2 participants | 4 participants |
| Region of Enrollment France | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Greece | 1 participants | 1 participants | 2 participants |
| Region of Enrollment Italy | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Romania | 4 participants | 4 participants | 8 participants |
| Region of Enrollment Spain | 3 participants | 3 participants | 6 participants |
| Region of Enrollment United Kingdom | 2 participants | 4 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 10 / 15 | 10 / 15 |
| serious Total, serious adverse events | 1 / 15 | 2 / 15 |
Outcome results
Primary
Percentage of Participants With Bone-Related Adverse Events and/or a ≥ 4% Reduction in Bone Mineral Density (BMD) From Baseline to Week 96
Time frame: Baseline to Week 96
Population: Participants in the Safety Analysis Set (participants who were randomized into the study and received at least one dose of tenofovir DF) with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF + Increased Bone/Renal Monitoring | Percentage of Participants With Bone-Related Adverse Events and/or a ≥ 4% Reduction in Bone Mineral Density (BMD) From Baseline to Week 96 | 6.7 percentage of participants |
| Tenofovir DF + Prespecified Bone Monitoring | Percentage of Participants With Bone-Related Adverse Events and/or a ≥ 4% Reduction in Bone Mineral Density (BMD) From Baseline to Week 96 | 0 percentage of participants |