Study to Evaluate the Antiviral Efficacy, Safety and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Participants With Chronic Hepatitis B Infection

Chronic Hepatitis B Clinical Trial

Official title:

A Randomized, Double-Blind Evaluation of the Antiviral Efficacy, Safety, and Tolerability of Tenofovir Disoproxil Fumarate Versus Placebo in Pediatric Patients With Chronic Hepatitis B Infection

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01651403
• Other study ID #: GS-US-174-0144
• Secondary ID: 2012-000586-20
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 6, 2012
• Est. completion date: July 2027

Study information

• Verified date: June 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: July 2027
• Est. primary completion date: August 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 11 Years

Eligibility

Key Inclusion Criteria:

• Male or Female, 2 to < 12 years of age
• Weight = 10 kg
• Chronic HBV infection = 6 months
• Hepatitis B e antigen (HBeAg)-positive or HBeAg-negative
• HBV Viral Load = 100,000 copies/mL
• Alanine aminotransferase (ALT) = 1.5 x the upper limit of the normal range (ULN) at screening
• Creatinine Clearance = 80 mL/min/1.73m^2
• Absolute neutrophil count (ANC) = 1,500/mm^3, hemoglobin = 10 g/dL
• Negative pregnancy test at screening
• 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)

Key Exclusion Criteria:

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Tenofovir DF
Participants weighing = 17 kg will receive TDF one tablet administered orally once daily (150, 200, 250 or 300 mg tablets based on body weight). Participants weighing < 17 kg or = 17 kg who are unable to swallow a tablet will receive TDF oral powder in a dose of 8 mg/kg once daily up to a maximum dose of 300 mg.
• TDF Placebo
Participants weighing = 17 kg will receive TDF placebo tablet administered orally once daily. Participants weighing < 17 kg or = 17 kg who are unable to swallow a tablet will receive TDF placebo oral powder once daily.

Locations

Country	Name	City	State
India	St. John Hospital & Medical Center	Bangalore
India	Medanta -The Medicity	Gurgaon	Haryana
India	SMS Medical College and Hospital	Jaipur	Rajasthan
India	M.V. Hospital and Research Centre 314/30 Mirza Mandi Chowk	Lucknow	Uttar Pradesh
India	Colors Children Hospital	Nagpur	Maharashtra
India	Nirmal Hospital Private Limited	Surat	Gujrat
Korea, Republic of	Kyungpook National University	Daegu
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Children's Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongnam
Romania	Fundeni Clinical Institute - Constantinesco	Bucharest
Romania	Grigore Alexandrescu Emergency Clinical Hospital for Children	Bucharest
Romania	Victor Babes Clinical Hospital of Infectious Diseases and Pneumophtisology	Craiova
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  India,  Korea, Republic of,  Romania,  Taiwan, 

References & Publications (1)

(Oral Presentation) Mei-Hwei Chang, Jae Hong Park, Jorge A. Bezerra, Daniela Pacura, Sandeep Nijhawan, Byung-Ho Choe, et al. Randomized, Double-Blind, Placebo-Controlled Trial of Tenofovir Disoproxil Fumarate (TDF) in Children with Chronic Hepatitis B (CH

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Failure Approach)		Week 48
Primary	Percentage of Participants With Serum HBV DNA < 400 Copies/mL (69 IU/mL) at Week 48 (Missing = Excluded Approach)		Week 48
Secondary	Percentage of Participants With Hepatitis B e Antigen (HBeAg) Seroconversion at Week 48	HBeAg seroconversion was defined as HBeAg loss and a change from HBeAb negative or missing at baseline to HBeAb positive.	Week 48
Secondary	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	Normal ALT was defined as = 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.	Week 48
Secondary	Percentage of Participants With Normal ALT at Week 192, Based on the AASLD Normal Range	Normal ALT was defined as = 30 U/L for males and females 0-12 years based on the AASLD pediatric normal range.	Week 192
Secondary	Percentage of Participants With Normal ALT at Week 48, Based on the Central Lab Normal Range	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.	Week 48
Secondary	Percentage of Participants With Normal ALT at Week 192, Based on the Central Lab Normal Range	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.	Week 192
Secondary	Percentage of Participants With Normalized ALT at Week 48, Based on the AASLD Normal Range	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.	Week 48
Secondary	Percentage of Participants With Normalized ALT at Week 192, Based on the AASLD Normal Range	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.	Week 192
Secondary	Percentage of Participants With Normalized ALT at Week 48, Based on the Central Lab Normal Range	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.	Week 48
Secondary	Percentage of Participants With Normalized ALT at Week 192, Based on the Central Lab Normal Range	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.	Week 192
Secondary	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	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.	Week 48
Secondary	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	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.	Week 192
Secondary	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	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.	Week 48
Secondary	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	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.	Week 192
Secondary	Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 48		Week 48
Secondary	Percentage of Participants With HBV DNA < 169 Copies/mL (29 IU/mL) at Week 192		Week 192
Secondary	Percentage of Participants With HBsAg Loss at Week 48	HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.	Week 48
Secondary	Percentage of Participants With HBsAg Loss at Week 192	HBsAg Loss was defined as a change from HBsAg positive or missing at baseline to HBsAg negative.	Week 192
Secondary	Percentage of Participants With HBsAg Seroconversion at Week 48	HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.	Week 48
Secondary	Percentage of Participants With HBsAg Seroconversion at Week 192	HBsAg seroconversion was defined as HBsAg loss and a change from HBsAb negative or missing at baseline to HBsAb positive.	Week 192
Secondary	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		Baseline; Week 48
Secondary	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		Baseline; Week 96
Secondary	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		Baseline; Week 144
Secondary	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		Baseline; Week 192
Secondary	Percentage of Participants With = 4% Decrease From Baseline in Spine Bone Mineral Density (BMD) at Week 48		Baseline; Week 48
Secondary	Percentage of Participants With = 4% Decrease From Baseline in Spine BMD at Week 192		Baseline; Week 192
Secondary	Percent Change From Baseline in BMD of Spine at Week 48		Baseline; Week 48
Secondary	Percent Change From Baseline in BMD of Spine at Week 192		Baseline; Week 192

External Links

•   Gilead Clinical Trials Website