N/A

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc., Gilead Sciences Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

6 Dec 2012 → 5 Jun 2025

Decision date (initial)

2024-11-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2024-517526-26-00

EudraCT number

2012-000586-20

ClinicalTrials.gov

NCT01651403

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy, Safety

To evaluate the antiviral efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) versus placebo in pediatric population (aged 2 to < 12 years at the time of enrollment) with chronic hepatitis B (CHB) infection.

Secondary objectives 5

1. To evaluate the proportion of subjects with HBeAg seroconversion at Week 72 (in subjects with baseline HBeAg sero-positivity)
2. To characterize the safety and tolerability profile of tenofovir DF in pediatric patients (aged 2 to < 12 years, at the time of enrollment) with chronic hepatitis B infection
3. To evaluate the biochemical and serological responses to tenofovir DF versus placebo
4. To evaluate the incidence of potential resistance mutations to tenofovir DF in the hepatitis B virus polymerase/reverse transcriptase (pol/RT)
5. To assess the pharmacokinetics of tenofovir in subjects receiving the tablet formulation and those receiving the oral powder formulation

Conditions and MedDRA coding

Hepatitis B Infection

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000533-PIP01-08

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or Female, 2 to < 12 years of age
2. Weight ≥ 10 kg
3. Chronic HBV infection ≥ 6 months
4. Hepatitis B e antigen (HBeAg)-positive or HBeAg-negative
5. HBV Viral Load ≥ 100,000 copies/mL
6. Alanine aminotransferase (ALT) ≥ 1.5 x the upper limit of the normal range (ULN) at screening
7. Creatinine Clearance ≥ 80 mL/min/1.73m^2
8. Absolute neutrophil count (ANC) ≥ 1,500/mm^3, hemoglobin ≥ 10 g/dL
9. Negative pregnancy test at screening
10. No prior tenofovir DF therapy (participants may have received prior interferon-alfa and/or other oral anti-HBV nucleoside/nucleotide therapy; participants must have discontinued interferon-alfa therapy ≥ 6 months prior to screening; participants experienced on other anti-HBV nucleoside/nucleotide therapy must have discontinued therapy ≥ 16 weeks prior to screening to avoid flare if randomized to the placebo arm)

Exclusion criteria 10

1. Pregnant or lactating
2. Decompensated liver disease
3. Received interferon therapy within 6 months of screening
4. Received anti-HBV nucleoside/nucleotide therapy within 16 weeks of screening
5. Alpha-fetoprotein levels > 50 ng/mL
6. Evidence of hepatocellular carcinoma (HCC)
7. Co-infection with human immunodeficiency virus (HIV), acute hepatitis A virus (HAV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
8. Chronic liver disease not due to HBV
9. History of significant renal, cardiovascular, pulmonary, neurological or bone disease
10. Long term non-steroidal, anti-inflammatory drug therapy Note: Other protocol defined Inclusion/Exclusion criteria may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach) [Time Frame: Week 48]
2. Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach) [Time Frame: Week 48]

Secondary endpoints 29

1. Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48 [Time Frame: Week 48] HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.
2. Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48, Based on the American Association for the Study of Liver Diseases (AASLD) Normal Range [Time Frame: Week 48] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.
3. Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.
4. Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.
5. Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range.
6. Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range [Time Frame: Week 48] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
7. Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
8. Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range [Time Frame: Week 48] Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
9. Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range [Time Frame: Week 192] Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
10. Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 48 [Time Frame: Week 48] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
11. Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on AASLD Normal Range) at Week 192 [Time Frame: Week 192] Normal ALT was defined as ≤ 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
12. Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 48 [Time Frame: Week 48]
13. Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
14. Composite Endpoint of Percentage of Participants With HBV DNA < 400 Copies/mL (69 IU/mL) and Normalized ALT (Based on Central Lab Normal Range) at Week 192 [Time Frame: Week 192]
15. Normal ALT was defined as ≤ 34 U/L for females aged 2-15 years old or males aged 1-9 years old, and ≤ 43 U/L for males aged 10-15 years old based on the central lab normal range. ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
16. Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48 [Time Frame: Week 48]
17. Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192 [Time Frame: Week 192]
18. Percentage of Participants With HBsAg Loss at Week 48 [Time Frame: Week 48] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.
19. Percentage of Participants With HBsAg Loss at Week 192 [Time Frame: Week 192] HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.
20. Percentage of Participants With HBsAg Seroconversion at Week 48 [Time Frame: Week 48] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.
21. Percentage of Participants With HBsAg Seroconversion at Week 192 [Time Frame: Week 192] HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.
22. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 48 [Time Frame: Baseline; Week 48]
23. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 96 [Time Frame: Baseline; Week 96]
24. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 144 [Time Frame: Baseline; Week 144]
25. Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Were Viremic (HBV DNA ≥ 400 Copies/mL [69 IU/mL]) Including Participants With Confirmed Virologic Breakthrough at Week 192 [Time Frame: Baseline; Week 192]
26. Percentage of Participants With ≥ 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48 [Time Frame: Baseline; Week 48]
27. Percentage of Participants With ≥ 4% Decrease From Baseline in Spine BMD at Week 192 [Time Frame: Baseline; Week 192]
28. Percent Change From Baseline in BMD of Spine at Week 48 [Time Frame: Baseline; Week 48]
29. Percent Change From Baseline in BMD of Spine at Week 192 [Time Frame: Baseline; Week 192]

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 4

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications