Evaluation of Tenofovir Disoproxil Fumarate in Adolescents With Chronic Hepatitis B Infection
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT00734162
Collaborator
(none)
106
21
2
84
5
0.1
Study Details
Study Description
Brief Summary
The primary purpose of the study is to evaluate the effectiveness, safety, and tolerability of tenofovir disoproxil fumarate (TDF) in adolescents (aged 12-17 years) with chronic hepatitis B virus (HBV) infection.
The optimal treatment for adolescents with chronic HBV infection is currently unknown. Treatment with interferon alfa, lamivudine, and adefovir dipivoxil in pediatric populations has been shown to be less than optimal. Further, the safety and efficacy of entecavir and telbivudine have not been established in patients < 16 years of age. A study evaluating TDF in adolescents (ages 12-17) was needed to assess the safety and efficacy of this agent in the treatment of chronic hepatitis B in this patient population. In addition, the study will help to further elucidate the pharmacokinetic (PK) and resistance profiles of TDF. Through their participation, study participants will help generate critical new information to help guide the most optimal treatment of chronic HBV infection in adolescents.
This is a randomized, double-blind study to evaluate the antiviral efficacy, safety, and tolerability of TDF versus placebo in adolescents with chronic HBV infection. TDF treatment-naive participants were randomized in a 1:1 ratio to TDF or placebo. After 72 weeks of blinded treatment, participants were to switch to open-label TDF for an additional 2.5 years of treatment, provided that no safety concerns are identified by the Independent Data Monitoring Committee monitoring the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
106 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, 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 Adolescents With Chronic Hepatitis B Infection
Study Start Date
:
Dec 1, 2008
Actual Primary Completion Date
:
Mar 1, 2011
Actual Study Completion Date
:
Dec 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tenofovir disoproxil fumarate (TDF)
|
Drug: Tenofovir disoproxil fumarate (TDF)
TDF administered as a 300-mg tablet once daily
Other Names:
|
| Placebo Comparator: Placebo
|
Drug: Placebo
TDF placebo tablet once daily
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72 [Week 72]
The percentage of participants with HBV DNA < 400 copies/mL at Week 72 was summarized by treatment and age group (grouped by baseline age for analysis), using the missing = failure (M = F) analysis with the double-blind efficacy evaluation (DBEE) algorithm. In the M = F analysis method, all missing data were considered as failure to meet the outcome measure threshold. This method was combined with the DBEE algorithm, which included all available data for the double-blind period, and any data for the open-label period were not included; data generated during treatment-free follow-up from subjects who achieved HBsAg loss and entered treatment-free follow-up during double-blind treatment period were included.
- Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72 [Baseline to Week 72]
Data were summarized by treatment and age group (grouped by baseline age for analysis). In contrast with what was previously reported in the interim results posting, 1 participant met the primary safety endpoint of at least a 6% decrease from baseline in spine BMD at Week 72, based on the final BMD data analysis. The apparent discrepancy was due to the correction factor applied to the subject-specific BMD calculations performed at the time of the Interim Week 72 clinical study report that could not take into account the actual Week 72 phantom data (ie, calibration test used in longitudinal clinical trials to monitor and adjust for shifts in the dual-energy x-ray absorptiometry (DXA) scanner calibration over time), which were not provided by the site at that time. The correction factor applied to the final analysis has been properly based on all phantom data through the end of Week 72, as well as through the end of Week 192.
Secondary Outcome Measures
- Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192 [Weeks 48, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192 [Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192 [Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192 [Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.
- Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F.
- Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192 [Baseline; Weeks 48, 96, 144, and 192]
The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48 [Baseline; Week 48]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Spine BMD at Week 72 [Baseline; Week 72]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Spine BMD at Week 96 [Baseline; Week 96]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Spine BMD at Week 144 [Baseline; Week 144]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Spine BMD at Week 192 [Baseline; Week 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Whole Body BMD at Week 48 [Baseline; Week 48]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Whole Body BMD at Week 72 [Baseline; Week 72]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Whole Body BMD at Week 96 [Baseline; Week 96]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Whole Body BMD at Week 144 [Baseline; Week 144]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Percent Change From Baseline in Whole Body BMD at Week 192 [Baseline; Week 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Spine BMD at Week 48 [Baseline; Week 48]
To assess any effect of treatment on growth, Z-scores were used to express the deviation from a reference population for lumbar spine BMD. A Z-score of 0 indicated that a subject was typical of the population for their age, ethnicity, and gender. A negative Z-score indicated that the subject's recorded value was lower than typical for their age, ethnicity, and gender. A positive Z-score indicates that the subject's recorded value was higher than typical for their age, ethnicity, and gender. Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Spine BMD at Week 72 [Baseline; Week 72]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Spine BMD at Week 96 [Baseline; Week 96]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Spine BMD at Week 144 [Baseline; Week 144]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Spine BMD at Week 192 [Baseline; Week 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Whole Body BMD at Week 48 [Baseline; Week 48]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Whole Body BMD at Week 72 [Baseline; Week 72]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Whole Body BMD at Week 96 [Baseline; Week 96]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Whole Body BMD at Week 144 [Baseline; Week 144]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Change From Baseline in Z-score for Whole Body BMD at Week 192 [Baseline; Week 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis).
- Number of Participants With Changes in Drug-Resistant Mutations During the Study [Baseline through Week 192]
The number of participants with changes in drug-resistant mutations during the study was summarized.
- Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
- Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192 [Baseline; Weeks 48, 72, 96, 144, and 192]
Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria
-
Male or female, 12 through 17 years of age, inclusive (consent of parent/legal guardian required)
-
Documented chronic HBV infection
-
HBeAg positive or HBeAg negative
-
Weight > 35 kg
-
Able to swallow oral tablets
-
HBV DNA > 100,000 copies/mL (polymerase chain reaction (PCR) method)
-
Alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN) at screening, OR any history of ALT > 2 × ULN over the past 24 months
-
Willing and able to provide written informed consent/assent (child and parent/legal guardian)
-
Negative serum pregnancy test (for postmenarchal females only)
-
Estimated glomerular filtration rate (creatinine clearance [using the Schwartz formula]) > 80 mL/min/1.73m^2
-
Adequate hematologic function (absolute neutrophil count ≥ 1,500/mm^3; hemoglobin ≥ 10.0 g/dL)
-
No prior TDF therapy (participants may have received prior interferon or oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon therapy ≥ 6 months prior to screening; participants experienced on 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 women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study
-
Males and females of reproductive potential who are not willing to use an effective method of contraception during the study
-
Decompensated liver disease
-
Receipt of interferon (pegylated or not) therapy within 6 months of the Screening Visit
-
Receipt of anti-HBV nucleoside/nucleotide therapy within 16 weeks of the Screening Visit
-
Alpha fetoprotein > 50 ng/mL
-
Evidence of hepatocellular carcinoma (HCC)
-
Coinfection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
-
History of significant renal disease (eg, nephrotic syndrome, renal dysgenesis, polycystic kidney disease, congenital nephrosis, acute tubular necrosis, other renal disease)
-
History of significant bone disease (eg, osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses, multiple bone fractures)
-
Significant cardiovascular, pulmonary, or neurological disease
-
Evidence of a gastrointestinal malabsorption syndrome that may interfere with absorption of orally administered medications
-
History of solid organ or bone marrow transplantation
-
Ongoing therapy with nephrotoxic agents, competitors of renal excretion, systemic chemotherapeutic agents, systemic corticosteroids, interleukin-2 (IL-2), or other immunomodulating or investigational agents
-
Known hypersensitivity to the study drugs, the metabolites or formulation excipients
-
Any other condition (including alcohol or substance abuse) or prior therapy that, in the opinion of the Investigator, would make the participants unsuitable for the study or unable to comply with dosing requirements
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital & Research Center at Oakland | Oakland | California | United States | 94609 |
| 2 | Riley Hospital for Children | Indianapolis | Indiana | United States | 46202 |
| 3 | Children's Hospital & Regional Medical Center, d/b/a Seattle Children's Research Institute | Seattle | Washington | United States | 98105 |
| 4 | Multiprofile Hospital for Active Treatment Sveti Georgi | Plovdiv | Bulgaria | 4002 | |
| 5 | Clinic of Gastroenterology, Specialized Hospital for Active Treatment of Pediatric Diseases, Sofia | Sofia | Bulgaria | 1606 | |
| 6 | Hopital Femmes Meres Enfants | Bron Cedex | France | 69677 | |
| 7 | Hôpital Claude Huriez | Lille Cedex | France | 59037 | |
| 8 | Samodzielny Publiczny Dzieciecy Szpital Kliniczny Akademii Medycznej w Bialymstoku | Białystok | Poland | 15-274 | |
| 9 | Wojewodzki Specjalistyczny Szpital im Bieganskiego | Bydgoszcz | Poland | 85-030 | |
| 10 | Wojewodzki Szpital Obserwacyjno-Zakazny im. T. Browicza | Bydgoszcz | Poland | 85-030 | |
| 11 | Krakowski Szpital Specjalistyczny im. Jana Pawla II | Kraków | Poland | 31-202 | |
| 12 | Samodzielny Publiczny Szpital Kliniczny im. Karola Johschera | Poznan | Poland | 60-572 | |
| 13 | Specjalistyczny Zespol Opieki Zdrowotnej nad Matka i Dzieckiem | Poznań | Poland | 61-734 | |
| 14 | Wojewodzki Szpital Zakazny | Warszawa | Poland | 01-201 | |
| 15 | Samodzielny Publiczny Szpital Kliniczny Nr 1 | Wrocław | Poland | 50-368 | |
| 16 | Fundeni Clinical Institute | Bucharest | Romania | 022328 | |
| 17 | Institute for Infectious Diseases | Bucharest | Romania | 21105 | |
| 18 | Cluj Childrens Emergency Hospital | Napaco | Romania | 400217 | |
| 19 | Hosp Univ y Politecnico La Fe de Valencia | Madrid | Spain | 28046 | |
| 20 | Hospital Universitario De Getafe | Madrid | Spain | 46009 | |
| 21 | Ege Universitesi Tip Fakultesi Hastanesi | Izmir | Turkey | 35100 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Benedetta Massetto, MD, PhD, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00734162
Other Study ID Numbers:
- GS-US-174-0115
First Posted:
Aug 14, 2008
Last Update Posted:
Sep 1, 2016
Last Verified:
Jul 1, 2016
Keywords provided by Gilead Sciences
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at 3 sites in the United States, 8 sites in Poland, 3 sites in Romania, 2 sites in Bulgaria, 2 sites in France, 2 sites in Spain, and 1 site in Turkey. The first participant was screened on 03 December 2008. The last study visit occurred on 02 December 2015. |
|---|---|
| Pre-assignment Detail | 149 participants were screened. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years |
|---|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate (TDF) 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Period Title: Randomized Phase (Through Week 72) | ||||
| STARTED | 10 | 42 | 13 | 41 |
| COMPLETED | 10 | 41 | 13 | 37 |
| NOT COMPLETED | 0 | 1 | 0 | 4 |
| Period Title: Randomized Phase (Through Week 72) | ||||
| STARTED | 10 | 41 | 13 | 39 |
| COMPLETED | 7 | 39 | 12 | 36 |
| NOT COMPLETED | 3 | 2 | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total |
|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | Total of all reporting groups |
| Overall Participants | 10 | 42 | 13 | 41 | 106 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
13.3
(0.82)
|
16.1
(0.75)
|
13.2
(0.69)
|
15.9
(0.82)
|
15.4
(1.38)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
30%
|
11
26.2%
|
4
30.8%
|
15
36.6%
|
33
31.1%
|
| Male |
7
70%
|
31
73.8%
|
9
69.2%
|
26
63.4%
|
73
68.9%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| Asian |
0
0%
|
1
2.4%
|
1
7.7%
|
0
0%
|
2
1.9%
|
| Black |
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
1
0.9%
|
| White |
10
100%
|
39
92.9%
|
12
92.3%
|
37
90.2%
|
98
92.5%
|
| Other |
0
0%
|
1
2.4%
|
0
0%
|
4
9.8%
|
5
4.7%
|
| Region of Enrollment (participants) [Number] | |||||
| Bulgaria |
0
0%
|
3
7.1%
|
3
23.1%
|
1
2.4%
|
7
6.6%
|
| France |
0
0%
|
1
2.4%
|
0
0%
|
1
2.4%
|
2
1.9%
|
| Poland |
6
60%
|
31
73.8%
|
6
46.2%
|
31
75.6%
|
74
69.8%
|
| Romania |
4
40%
|
4
9.5%
|
2
15.4%
|
4
9.8%
|
14
13.2%
|
| Spain |
0
0%
|
0
0%
|
0
0%
|
2
4.9%
|
2
1.9%
|
| Turkey |
0
0%
|
1
2.4%
|
1
7.7%
|
0
0%
|
2
1.9%
|
| United States |
0
0%
|
2
4.8%
|
1
7.7%
|
2
4.9%
|
5
4.7%
|
| Region of Enrollment (participants) [Number] | |||||
| Europe |
10
100%
|
40
95.2%
|
12
92.3%
|
39
95.1%
|
101
95.3%
|
| North America |
0
0%
|
2
4.8%
|
1
7.7%
|
2
4.9%
|
5
4.7%
|
| Alanine aminotransferase (ALT) level at baseline (U/L) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [U/L] |
77
(54.8)
|
106
(116.4)
|
101
(95.4)
|
101
(89.5)
|
101
(98.5)
|
| ALT normal at baseline (participants) [Number] | |||||
| Normal |
3
30%
|
14
33.3%
|
4
30.8%
|
8
19.5%
|
29
27.4%
|
| Abnormal |
7
70%
|
28
66.7%
|
9
69.2%
|
33
80.5%
|
77
72.6%
|
| HBV Genotype (participants) [Number] | |||||
| Genotype A |
5
50%
|
30
71.4%
|
5
38.5%
|
29
70.7%
|
69
65.1%
|
| Genotype B |
0
0%
|
1
2.4%
|
1
7.7%
|
1
2.4%
|
3
2.8%
|
| Genotype C |
0
0%
|
1
2.4%
|
0
0%
|
0
0%
|
1
0.9%
|
| Genotype D |
5
50%
|
10
23.8%
|
7
53.8%
|
11
26.8%
|
33
31.1%
|
| Hepatitis B e Antigen (HBeAg) status at baseline (participants) [Number] | |||||
| Negative |
1
10%
|
3
7.1%
|
0
0%
|
6
14.6%
|
10
9.4%
|
| Positive |
9
90%
|
39
92.9%
|
13
100%
|
35
85.4%
|
96
90.6%
|
| HBV DNA level at baseline (Log_10 copies/mL) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Log_10 copies/mL] |
8.26
(1.455)
|
7.95
(1.421)
|
8.61
(1.166)
|
8.12
(1.451)
|
8.13
(1.403)
|
Outcome Measures
| Title | Percentage of Participants With HBV DNA < 400 Copies/mL at Week 72 |
|---|---|
| Description | The percentage of participants with HBV DNA < 400 copies/mL at Week 72 was summarized by treatment and age group (grouped by baseline age for analysis), using the missing = failure (M = F) analysis with the double-blind efficacy evaluation (DBEE) algorithm. In the M = F analysis method, all missing data were considered as failure to meet the outcome measure threshold. This method was combined with the DBEE algorithm, which included all available data for the double-blind period, and any data for the open-label period were not included; data generated during treatment-free follow-up from subjects who achieved HBsAg loss and entered treatment-free follow-up during double-blind treatment period were included. |
| Time Frame | Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: participants who were randomized and received at least one dose of study drug |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Number [percentage of participants] |
90.0
900%
|
88.1
209.8%
|
0
0%
|
0
0%
|
88.5
83.5%
|
0
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TDF 12-14 Years, TDF 15-17 Years, Placebo 12-14 Years, Placebo 15-17 Years |
|---|---|---|
| Comments | Analysis is the difference between treatment groups in the proportion of participants who met the outcome measure criterion, controlling for randomization age group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.001 |
| Comments | A p-value of < 0.05 was considered statistically significant. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Percentage of Participants With at Least a 6% Decrease From Baseline in Bone Mineral Density (BMD) of the Spine at Week 72 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). In contrast with what was previously reported in the interim results posting, 1 participant met the primary safety endpoint of at least a 6% decrease from baseline in spine BMD at Week 72, based on the final BMD data analysis. The apparent discrepancy was due to the correction factor applied to the subject-specific BMD calculations performed at the time of the Interim Week 72 clinical study report that could not take into account the actual Week 72 phantom data (ie, calibration test used in longitudinal clinical trials to monitor and adjust for shifts in the dual-energy x-ray absorptiometry (DXA) scanner calibration over time), which were not provided by the site at that time. The correction factor applied to the final analysis has been properly based on all phantom data through the end of Week 72, as well as through the end of Week 192. |
| Time Frame | Baseline to Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: participants who received at least one dose of study drug. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Number [percentage of participants] |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Title | Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Weeks 48, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
90.0
900%
|
85.7
204%
|
0
0%
|
0
0%
|
86.5
81.6%
|
0
NaN
|
| Week 96 |
90.0
900%
|
88.1
209.8%
|
53.8
413.8%
|
68.3
166.6%
|
88.5
83.5%
|
64.8
NaN
|
| Week 144 |
100.0
1000%
|
90.5
215.5%
|
69.2
532.3%
|
85.4
208.3%
|
92.3
87.1%
|
81.5
NaN
|
| Week 192 |
90.0
900%
|
85.7
204%
|
76.9
591.5%
|
73.2
178.5%
|
86.5
81.6%
|
74.1
NaN
|
| Title | Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
70.0
700%
|
76.2
181.4%
|
30.8
236.9%
|
26.8
65.4%
|
75.0
70.8%
|
27.8
NaN
|
| Week 72 |
80.0
800%
|
76.2
181.4%
|
30.8
236.9%
|
41.5
101.2%
|
76.9
72.5%
|
38.9
NaN
|
| Week 96 |
80.0
800%
|
76.2
181.4%
|
69.2
532.3%
|
65.9
160.7%
|
76.9
72.5%
|
66.7
NaN
|
| Week 144 |
60.0
600%
|
71.4
170%
|
69.2
532.3%
|
75.6
184.4%
|
69.2
65.3%
|
74.1
NaN
|
| Week 192 |
80.0
800%
|
71.4
170%
|
84.6
650.8%
|
75.6
184.4%
|
73.1
69%
|
77.8
NaN
|
| Title | Percentage of Participants With HBV DNA < 400 Copies/mL and Normal ALT at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
70.0
700%
|
69.0
164.3%
|
0
0%
|
0
0%
|
69.2
65.3%
|
0
NaN
|
| Week 72 |
80.0
800%
|
69.0
164.3%
|
0
0%
|
0
0%
|
71.2
67.2%
|
0
NaN
|
| Week 96 |
80.0
800%
|
73.8
175.7%
|
46.2
355.4%
|
51.2
124.9%
|
75.0
70.8%
|
50.0
NaN
|
| Week 144 |
60.0
600%
|
69.0
164.3%
|
53.8
413.8%
|
68.3
166.6%
|
67.3
63.5%
|
64.8
NaN
|
| Week 192 |
80.0
800%
|
64.3
153.1%
|
69.2
532.3%
|
63.4
154.6%
|
67.3
63.5%
|
64.8
NaN
|
| Title | Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
80.0
800%
|
81.0
192.9%
|
0
0%
|
0
0%
|
80.8
76.2%
|
0
NaN
|
| Week 72 |
90.0
900%
|
83.3
198.3%
|
0
0%
|
0
0%
|
84.6
79.8%
|
0
NaN
|
| Week 96 |
90.0
900%
|
88.1
209.8%
|
53.8
413.8%
|
63.4
154.6%
|
88.5
83.5%
|
61.1
NaN
|
| Week 144 |
90.0
900%
|
88.1
209.8%
|
69.2
532.3%
|
82.9
202.2%
|
88.5
83.5%
|
79.6
NaN
|
| Week 192 |
90.0
900%
|
83.3
198.3%
|
76.9
591.5%
|
73.2
178.5%
|
84.6
79.8%
|
74.1
NaN
|
| Title | Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 72 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 96 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 144 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 192 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Title | Percentage of Participants With HBsAg Seroconversion at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | HBsAg seroconversion was defined as change of detectable antibody to HBsAg from negative to positive. Data were summarized by treatment and age group (grouped by baseline age for analysis), using the M = F. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 72 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 96 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 144 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 192 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Title | Percentage of Participants With at Least a 6% Decrease From Baseline in Spine BMD at Weeks 48, 96, 144, and 192 |
|---|---|
| Description | The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Weeks 48, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 96 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 144 |
0
0%
|
2.4
5.7%
|
0
0%
|
0
0%
|
1.9
1.8%
|
0
NaN
|
| Week 192 |
0
0%
|
4.8
11.4%
|
0
0%
|
4.9
12%
|
3.8
3.6%
|
3.7
NaN
|
| Title | Percentage of Participants With at Least a 6% Decrease From Baseline in Whole Body BMD at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | The percentage of participants reported is the cumulative incidence from baseline to the respective time point. Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 42 | 13 | 41 | 52 | 54 |
| Week 48 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 72 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 96 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
NaN
|
| Week 144 |
0
0%
|
0
0%
|
0
0%
|
2.4
5.9%
|
0
0%
|
1.9
NaN
|
| Week 192 |
0
0%
|
0
0%
|
0
0%
|
2.4
5.9%
|
0
0%
|
1.9
NaN
|
| Title | Percent Change From Baseline in Spine Bone Mineral Density (BMD) at Week 48 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 41 | 12 | 37 | 51 | 49 |
| Mean (Standard Deviation) [percentage change] |
9.234
(3.4782)
|
2.114
(3.6023)
|
9.038
(6.6575)
|
4.435
(4.9091)
|
3.510
(4.5507)
|
5.562
(5.6772)
|
| Title | Percent Change From Baseline in Spine BMD at Week 72 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 41 | 12 | 37 | 51 | 49 |
| Mean (Standard Deviation) [percentage change] |
11.516
(3.8818)
|
3.589
(4.5633)
|
14.131
(9.9563)
|
6.117
(6.0624)
|
5.144
(5.4291)
|
8.080
(7.8996)
|
| Title | Percent Change From Baseline in Spine BMD at Week 96 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 40 | 11 | 39 | 50 | 50 |
| Mean (Standard Deviation) [percentage change] |
13.811
(4.6712)
|
4.196
(4.8021)
|
16.687
(10.4359)
|
4.272
(7.0463)
|
6.119
(6.1200)
|
7.003
(9.3658)
|
| Title | Percent Change From Baseline in Spine BMD at Week 144 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 39 | 10 | 38 | 49 | 48 |
| Mean (Standard Deviation) [percentage change] |
19.224
(8.7594)
|
5.289
(5.8084)
|
21.346
(13.4709)
|
6.144
(8.3286)
|
8.133
(8.5611)
|
9.311
(11.3262)
|
| Title | Percent Change From Baseline in Spine BMD at Week 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 37 | 11 | 35 | 46 | 46 |
| Mean (Standard Deviation) [percentage change] |
23.933
(8.5166)
|
6.673
(7.2870)
|
25.036
(14.2346)
|
6.867
(9.3736)
|
10.050
(10.1637)
|
11.212
(13.1459)
|
| Title | Percent Change From Baseline in Whole Body BMD at Week 48 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 39 | 13 | 37 | 48 | 50 |
| Mean (Standard Deviation) [percentage change] |
5.123
(3.8309)
|
1.339
(1.9324)
|
5.470
(3.4958)
|
3.236
(2.8573)
|
2.048
(2.7830)
|
3.817
(3.1576)
|
| Title | Percent Change From Baseline in Whole Body BMD at Week 72 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 41 | 13 | 38 | 50 | 51 |
| Mean (Standard Deviation) [percentage change] |
7.282
(3.9156)
|
2.141
(2.6284)
|
8.480
(4.4770)
|
4.335
(3.4073)
|
3.067
(3.4819)
|
5.391
(4.0902)
|
| Title | Percent Change From Baseline in Whole Body BMD at Week 96 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 40 | 12 | 38 | 49 | 50 |
| Mean (Standard Deviation) [percentage change] |
8.034
(3.4973)
|
3.023
(3.2063)
|
10.056
(5.4296)
|
4.291
(4.3195)
|
3.943
(3.7730)
|
5.675
(5.1858)
|
| Title | Percent Change From Baseline in Whole Body BMD at Week 144 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 38 | 11 | 38 | 47 | 49 |
| Mean (Standard Deviation) [percentage change] |
10.940
(4.8819)
|
3.529
(3.1734)
|
12.638
(5.9973)
|
4.730
(5.2213)
|
4.949
(4.5753)
|
6.505
(6.2944)
|
| Title | Percent Change From Baseline in Whole Body BMD at Week 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 8 | 35 | 12 | 34 | 43 | 46 |
| Mean (Standard Deviation) [percentage change] |
13.923
(4.6139)
|
4.295
(3.7318)
|
14.797
(6.4993)
|
4.549
(5.4494)
|
6.086
(5.4029)
|
7.223
(7.2666)
|
| Title | Change From Baseline in Z-score for Spine BMD at Week 48 |
|---|---|
| Description | To assess any effect of treatment on growth, Z-scores were used to express the deviation from a reference population for lumbar spine BMD. A Z-score of 0 indicated that a subject was typical of the population for their age, ethnicity, and gender. A negative Z-score indicated that the subject's recorded value was lower than typical for their age, ethnicity, and gender. A positive Z-score indicates that the subject's recorded value was higher than typical for their age, ethnicity, and gender. Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 41 | 12 | 37 | 51 | 49 |
| Mean (Standard Deviation) [z-score] |
0.02
(0.247)
|
-0.10
(0.255)
|
0.04
(0.393)
|
0.05
(0.322)
|
-0.08
(0.256)
|
0.05
(0.337)
|
| Title | Change From Baseline in Z-score for Spine BMD at Week 72 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 41 | 12 | 37 | 51 | 49 |
| Mean (Standard Deviation) [z-score] |
-0.10
(0.312)
|
-0.05
(0.325)
|
0.09
(0.498)
|
0.10
(0.339)
|
-0.06
(0.320)
|
0.10
(0.378)
|
| Title | Change From Baseline in Z-score for Spine BMD at Week 96 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 40 | 11 | 39 | 50 | 50 |
| Mean (Standard Deviation) [z-score] |
-0.19
(0.365)
|
-0.07
(0.356)
|
-0.02
(0.498)
|
-0.13
(0.414)
|
-0.10
(0.357)
|
-0.11
(0.431)
|
| Title | Change From Baseline in Z-score for Spine BMD at Week 144 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 10 | 39 | 10 | 38 | 49 | 48 |
| Mean (Standard Deviation) [z-score] |
-0.20
(0.560)
|
-0.05
(0.417)
|
-0.16
(0.625)
|
-0.04
(0.405)
|
-0.08
(0.447)
|
-0.06
(0.455)
|
| Title | Change From Baseline in Z-score for Spine BMD at Week 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 37 | 11 | 35 | 46 | 46 |
| Mean (Standard Deviation) [z-score] |
-0.24
(0.518)
|
0.08
(0.544)
|
-0.26
(0.654)
|
-0.05
(0.504)
|
0.02
(0.548)
|
-0.10
(0.543)
|
| Title | Change From Baseline in Z-score for Whole Body BMD at Week 48 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 39 | 13 | 37 | 48 | 50 |
| Mean (Standard Deviation) [z-score] |
0.02
(0.426)
|
-0.15
(0.257)
|
0.10
(0.370)
|
0.04
(0.308)
|
-0.12
(0.298)
|
0.05
(0.322)
|
| Title | Change From Baseline in Z-score for Whole Body BMD at Week 72 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 41 | 13 | 38 | 50 | 51 |
| Mean (Standard Deviation) [z-score] |
0.02
(0.398)
|
-0.19
(0.338)
|
0.20
(0.450)
|
0.06
(0.306)
|
-0.16
(0.355)
|
0.09
(0.349)
|
| Title | Change From Baseline in Z-score for Whole Body BMD at Week 96 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 96 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 40 | 12 | 38 | 49 | 50 |
| Mean (Standard Deviation) [z-score] |
-0.12
(0.294)
|
-0.19
(0.451)
|
0.09
(0.528)
|
-0.06
(0.432)
|
-0.18
(0.424)
|
-0.03
(0.456)
|
| Title | Change From Baseline in Z-score for Whole Body BMD at Week 144 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 144 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 38 | 11 | 38 | 47 | 49 |
| Mean (Standard Deviation) [z-score] |
-0.27
(0.431)
|
-0.21
(0.473)
|
-0.06
(0.554)
|
-0.16
(0.468)
|
-0.22
(0.462)
|
-0.14
(0.484)
|
| Title | Change From Baseline in Z-score for Whole Body BMD at Week 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis). |
| Time Frame | Baseline; Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Safety Analysis Set with available data were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 8 | 35 | 12 | 34 | 43 | 46 |
| Mean (Standard Deviation) [z-score] |
-0.34
(0.499)
|
-0.11
(0.524)
|
-0.21
(0.486)
|
-0.19
(0.517)
|
-0.16
(0.521)
|
-0.19
(0.504)
|
| Title | Number of Participants With Changes in Drug-Resistant Mutations During the Study |
|---|---|
| Description | The number of participants with changes in drug-resistant mutations during the study was summarized. |
| Time Frame | Baseline through Week 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with HBV DNA ≥ 400 copies/mL, with confirmed virologic breakthrough (defined as 2 consecutive increases in HBV DNA of at least 10-fold from nadir, or confirmed values ≥ 400 copies/mL after being < 400 copies/mL while on study medication), or subjects who discontinued early (after Week 24 with HBV DNA ≥ 400 copies/mL) were analyzed. |
| Arm/Group Title | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 52 | 54 |
| New TDF Drug-Resistant Mutations |
0
0%
|
0
0%
|
| Enrichment of TDF Drug-Resistant Mutations |
0
0%
|
0
0%
|
| Title | Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Loss at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set who were HBeAg-positive at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 39 | 13 | 35 | 48 | 48 |
| Week 48 |
11.1
111%
|
17.9
42.6%
|
7.7
59.2%
|
8.6
21%
|
16.7
15.8%
|
8.3
NaN
|
| Week 72 |
11.1
111%
|
23.1
55%
|
23.1
177.7%
|
11.4
27.8%
|
20.8
19.6%
|
14.6
NaN
|
| Week 96 |
44.4
444%
|
30.8
73.3%
|
38.5
296.2%
|
28.6
69.8%
|
33.3
31.4%
|
31.3
NaN
|
| Week 144 |
44.4
444%
|
38.5
91.7%
|
53.8
413.8%
|
34.3
83.7%
|
39.6
37.4%
|
39.6
NaN
|
| Week 192 |
33.3
333%
|
43.6
103.8%
|
53.8
413.8%
|
37.1
90.5%
|
41.7
39.3%
|
41.7
NaN
|
| Title | Percentage of Participants Who Were HBeAg-Positive at Baseline and Who Had HBeAg Seroconversion at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set who were HBeAg-positive at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 39 | 13 | 35 | 48 | 48 |
| Week 48 |
11.1
111%
|
15.4
36.7%
|
7.7
59.2%
|
8.6
21%
|
14.6
13.8%
|
8.3
NaN
|
| Week 72 |
11.1
111%
|
23.1
55%
|
23.1
177.7%
|
11.4
27.8%
|
20.8
19.6%
|
14.6
NaN
|
| Week 96 |
44.4
444%
|
30.8
73.3%
|
38.5
296.2%
|
25.7
62.7%
|
33.3
31.4%
|
29.2
NaN
|
| Week 144 |
33.3
333%
|
38.5
91.7%
|
53.8
413.8%
|
34.3
83.7%
|
37.5
35.4%
|
39.6
NaN
|
| Week 192 |
33.3
333%
|
38.5
91.7%
|
53.8
413.8%
|
37.1
90.5%
|
37.5
35.4%
|
41.7
NaN
|
| Title | Percentage of Participants Who Were HBeAg-Positive at Baseline Who Had HBV DNA < 400 Copies/mL, Normal ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set who were HBeAg-positive at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 9 | 39 | 13 | 35 | 48 | 48 |
| Week 48 |
11.1
111%
|
12.8
30.5%
|
0
0%
|
0
0%
|
12.5
11.8%
|
0
NaN
|
| Week 72 |
11.1
111%
|
15.4
36.7%
|
0
0%
|
0
0%
|
14.6
13.8%
|
0
NaN
|
| Week 96 |
44.4
444%
|
28.2
67.1%
|
30.8
236.9%
|
22.9
55.9%
|
31.3
29.5%
|
25.0
NaN
|
| Week 144 |
22.2
222%
|
30.8
73.3%
|
46.2
355.4%
|
25.7
62.7%
|
29.2
27.5%
|
31.3
NaN
|
| Week 192 |
33.3
333%
|
28.2
67.1%
|
46.2
355.4%
|
25.7
62.7%
|
29.2
27.5%
|
31.3
NaN
|
| Title | Percentage of Participants With Abnormal ALT at Baseline Who Had Normalized ALT at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with abnormal ALT at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 7 | 28 | 9 | 33 | 35 | 42 |
| Week 48 |
85.7
857%
|
71.4
170%
|
11.1
85.4%
|
21.2
51.7%
|
74.3
70.1%
|
19.0
NaN
|
| Week 72 |
85.7
857%
|
71.4
170%
|
22.2
170.8%
|
33.3
81.2%
|
74.3
70.1%
|
31.0
NaN
|
| Week 96 |
85.7
857%
|
78.6
187.1%
|
66.7
513.1%
|
63.6
155.1%
|
80.0
75.5%
|
64.3
NaN
|
| Week 144 |
57.1
571%
|
71.4
170%
|
66.7
513.1%
|
72.7
177.3%
|
68.6
64.7%
|
71.4
NaN
|
| Week 192 |
85.7
857%
|
75.0
178.6%
|
77.8
598.5%
|
69.7
170%
|
77.1
72.7%
|
71.4
NaN
|
| Title | Percentage of Participants With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL and Normalized ALT at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with abnormal ALT at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 7 | 28 | 9 | 33 | 35 | 42 |
| Week 48 |
85.7
857%
|
71.4
170%
|
0
0%
|
0
0%
|
74.3
70.1%
|
0
NaN
|
| Week 72 |
85.7
857%
|
71.4
170%
|
0
0%
|
0
0%
|
74.3
70.1%
|
0
NaN
|
| Week 96 |
85.7
857%
|
78.6
187.1%
|
55.6
427.7%
|
54.5
132.9%
|
80.0
75.5%
|
54.8
NaN
|
| Week 144 |
57.1
571%
|
71.4
170%
|
66.7
513.1%
|
69.7
170%
|
68.6
64.7%
|
69.0
NaN
|
| Week 192 |
85.7
857%
|
67.9
161.7%
|
77.8
598.5%
|
57.6
140.5%
|
71.4
67.4%
|
61.9
NaN
|
| Title | Percentage of Participants Who Were HBeAg-Positive With Abnormal ALT at Baseline Who Had HBV DNA < 400 Copies/mL, Normalized ALT, and HBeAg Loss/Seroconversion at Weeks 48, 72, 96, 144, and 192 |
|---|---|
| Description | Data were summarized by treatment and age group (grouped by baseline age for analysis) using the missing = failure method. |
| Time Frame | Baseline; Weeks 48, 72, 96, 144, and 192 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set who were HBeAg-Positive with abnormal ALT at baseline were analyzed. |
| Arm/Group Title | TDF 12-14 Years | TDF 15-17 Years | Placebo 12-14 Years | Placebo 15-17 Years | Total TDF 12-17 Years | Total Placebo 12-17 Years |
|---|---|---|---|---|---|---|
| Arm/Group Description | TDF 300 mg tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-14 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 15-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF 300 mg tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase | TDF placebo tablet once daily in participants 12-17 years of age in the Randomized Phase, followed by TDF 300 mg tablet once daily in the Open-Label Phase |
| Measure Participants | 6 | 27 | 9 | 33 | 33 | 42 |
| Week 48 |
16.7
167%
|
18.5
44%
|
0
0%
|
0
0%
|
18.2
17.2%
|
0
NaN
|
| Week 72 |
16.7
167%
|
22.2
52.9%
|
0
0%
|
0
0%
|
21.2
20%
|
0
NaN
|
| Week 96 |
50.0
500%
|
33.3
79.3%
|
33.3
256.2%
|
24.2
59%
|
36.4
34.3%
|
26.2
NaN
|
| Week 144 |
33.3
333%
|
29.6
70.5%
|
55.6
427.7%
|
27.3
66.6%
|
30.3
28.6%
|
33.3
NaN
|
| Week 192 |
50.0
500%
|
29.6
70.5%
|
55.6
427.7%
|
27.3
66.6%
|
33.3
31.4%
|
33.3
NaN
|
Adverse Events
| Time Frame | Baseline through end of the Open-Label Phase (up to 4 years) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set | |||||||
| Arm/Group Title | Double-Blind TDF | Double-Blind Placebo | Open-Label TDF-TDF | Open-Label Placebo-TDF | ||||
| Arm/Group Description | Adverse events reported in this group occurred during the Randomized Phase (+7 days for participants who did not continue to the Open-Label Phase) and includes all participants who received double-blind TDF during the Randomized Phase of the study. | Adverse events reported in this group occurred during the Randomized Phase (+7 days for participants who did not continue to the Open-Label Phase) and includes all participants who received placebo during the Randomized Phase of the study. | Adverse events reported in this group occurred during the Open-Label Phase and includes all participants who received double-blind TDF during the Randomized Phase of the study and continued to the Open-Label Phase. | Adverse events reported in this group occurred during the Open-Label Phase and includes all participants who received placebo during the Randomized Phase of the study and continued to the Open-Label Phase. | ||||
All Cause Mortality |
||||||||
| Double-Blind TDF | Double-Blind Placebo | Open-Label TDF-TDF | Open-Label Placebo-TDF | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Double-Blind TDF | Double-Blind Placebo | Open-Label TDF-TDF | Open-Label Placebo-TDF | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/52 (9.6%) | 11/54 (20.4%) | 8/51 (15.7%) | 10/52 (19.2%) | ||||
| Cardiac disorders | ||||||||
| Bradycardia | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Ventricular extrasystoles | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Phimosis | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/52 (0%) | 1/54 (1.9%) | 1/51 (2%) | 1/52 (1.9%) | ||||
| Gastritis | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Gastroduodenitis | 1/52 (1.9%) | 0/54 (0%) | 0/51 (0%) | 0/52 (0%) | ||||
| Peptic ulcer perforation | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatitis | 1/52 (1.9%) | 7/54 (13%) | 1/51 (2%) | 0/52 (0%) | ||||
| Infections and infestations | ||||||||
| Appendicitis | 1/52 (1.9%) | 0/54 (0%) | 0/51 (0%) | 0/52 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Hand fracture | 1/52 (1.9%) | 0/54 (0%) | 0/51 (0%) | 0/52 (0%) | ||||
| Jaw fracture | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Ligament sprain | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Multiple injuries | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Patella fracture | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Wound | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase abnormal | 0/52 (0%) | 1/54 (1.9%) | 0/51 (0%) | 0/52 (0%) | ||||
| Alanine aminotransferase increased | 0/52 (0%) | 1/54 (1.9%) | 0/51 (0%) | 3/52 (5.8%) | ||||
| Aspartate aminotransferase increased | 0/52 (0%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Blood creatinine increased | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Glucose urine present | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Protein urine present | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Nervous system disorders | ||||||||
| Syncope | 1/52 (1.9%) | 0/54 (0%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Drug dependence | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal colic | 0/52 (0%) | 1/54 (1.9%) | 0/51 (0%) | 0/52 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Menstrual disorder | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 0/52 (0%) | 1/54 (1.9%) | 0/51 (0%) | 0/52 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/52 (0%) | 0/54 (0%) | 1/51 (2%) | 0/52 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Double-Blind TDF | Double-Blind Placebo | Open-Label TDF-TDF | Open-Label Placebo-TDF | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/52 (65.4%) | 40/54 (74.1%) | 30/51 (58.8%) | 31/52 (59.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Lymphadenopathy | 0/52 (0%) | 5/54 (9.3%) | 1/51 (2%) | 0/52 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 3/52 (5.8%) | 7/54 (13%) | 1/51 (2%) | 9/52 (17.3%) | ||||
| Constipation | 1/52 (1.9%) | 3/54 (5.6%) | 0/51 (0%) | 0/52 (0%) | ||||
| Diarrhoea | 4/52 (7.7%) | 1/54 (1.9%) | 3/51 (5.9%) | 2/52 (3.8%) | ||||
| Nausea | 2/52 (3.8%) | 3/54 (5.6%) | 0/51 (0%) | 2/52 (3.8%) | ||||
| Toothache | 1/52 (1.9%) | 3/54 (5.6%) | 1/51 (2%) | 1/52 (1.9%) | ||||
| Vomiting | 0/52 (0%) | 3/54 (5.6%) | 0/51 (0%) | 0/52 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 4/52 (7.7%) | 1/54 (1.9%) | 1/51 (2%) | 2/52 (3.8%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 2/52 (3.8%) | 1/54 (1.9%) | 6/51 (11.8%) | 4/52 (7.7%) | ||||
| Gastroenteritis | 2/52 (3.8%) | 2/54 (3.7%) | 0/51 (0%) | 5/52 (9.6%) | ||||
| Herpes zoster | 0/52 (0%) | 3/54 (5.6%) | 0/51 (0%) | 0/52 (0%) | ||||
| Nasopharyngitis | 5/52 (9.6%) | 12/54 (22.2%) | 6/51 (11.8%) | 12/52 (23.1%) | ||||
| Pharyngitis | 15/52 (28.8%) | 11/54 (20.4%) | 9/51 (17.6%) | 13/52 (25%) | ||||
| Respiratory tract infection | 1/52 (1.9%) | 2/54 (3.7%) | 1/51 (2%) | 3/52 (5.8%) | ||||
| Rhinitis | 5/52 (9.6%) | 3/54 (5.6%) | 3/51 (5.9%) | 1/52 (1.9%) | ||||
| Tonsillitis | 2/52 (3.8%) | 4/54 (7.4%) | 2/51 (3.9%) | 4/52 (7.7%) | ||||
| Upper respiratory tract infection | 5/52 (9.6%) | 7/54 (13%) | 3/51 (5.9%) | 7/52 (13.5%) | ||||
| Viral infection | 0/52 (0%) | 0/54 (0%) | 4/51 (7.8%) | 2/52 (3.8%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 1/52 (1.9%) | 3/54 (5.6%) | 0/51 (0%) | 0/52 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/52 (3.8%) | 5/54 (9.3%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Blood creatine phosphokinase increased | 3/52 (5.8%) | 0/54 (0%) | 2/51 (3.9%) | 1/52 (1.9%) | ||||
| Nervous system disorders | ||||||||
| Headache | 2/52 (3.8%) | 9/54 (16.7%) | 1/51 (2%) | 2/52 (3.8%) | ||||
| Reproductive system and breast disorders | ||||||||
| Dysmenorrhoea | 0/52 (0%) | 4/54 (7.4%) | 0/51 (0%) | 3/52 (5.8%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 3/52 (5.8%) | 3/54 (5.6%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Epistaxis | 3/52 (5.8%) | 2/54 (3.7%) | 0/51 (0%) | 0/52 (0%) | ||||
| Oropharyngeal pain | 0/52 (0%) | 5/54 (9.3%) | 0/51 (0%) | 1/52 (1.9%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 2/52 (3.8%) | 10/54 (18.5%) | 2/51 (3.9%) | 6/52 (11.5%) | ||||
| Nail disorder | 3/52 (5.8%) | 0/54 (0%) | 0/51 (0%) | 0/52 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years
Results Point of Contact
| Name/Title | Clinical Trial Disclosures |
|---|---|
| Organization | Gilead Sciences |
| Phone | |
| ClinicalTrialDisclosures@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00734162
Other Study ID Numbers:
- GS-US-174-0115
First Posted:
Aug 14, 2008
Last Update Posted:
Sep 1, 2016
Last Verified:
Jul 1, 2016