TAF for Chronic Hepatitis B

Not currently recruiting at 51 trial locations

Overseen By Gilead Study Team

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Immunomodulators, Immunosuppressants

Disqualifiers: Pregnancy, Hepatitis C, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called tenofovir alafenamide (TAF) for children and teens with chronic hepatitis B, a long-lasting liver infection. The researchers aim to assess the safety and effectiveness of TAF compared to a placebo (a pill with no active drug) and determine the best dose for young patients. Children and teens diagnosed with chronic hepatitis B for at least six months and meeting certain liver test criteria might be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently receiving therapy with immunomodulators or immunosuppressants. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tenofovir alafenamide (TAF) has been well-studied in adults with chronic hepatitis B. In a study with 1,298 people, researchers found TAF to be generally safe and well-tolerated over 96 weeks. Common side effects included headache, stomach pain, and tiredness, while serious side effects were rare. Another study demonstrated that TAF remained effective and safe over eight years.

The FDA has approved TAF for use in adults with chronic hepatitis B, indicating a strong safety record. However, its safety in children under six years old remains unknown. This trial aims to provide more information about how children and teens handle TAF. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic hepatitis B?

Researchers are excited about Tenofovir Alafenamide (TAF) because it offers a new way to tackle chronic Hepatitis B, especially in younger patients. Unlike the standard treatments like Tenofovir Disoproxil Fumarate (TDF), TAF is designed to be more targeted, allowing for lower doses with potentially fewer side effects. This is particularly important for children, as TAF's dosing can be adjusted based on weight, providing a more personalized treatment approach. Additionally, TAF might offer a longer-term treatment option with its open-label extension, which could mean extended effectiveness and improved patient outcomes.

What evidence suggests that Tenofovir Alafenamide (TAF) might be an effective treatment for chronic hepatitis B?

Research shows that tenofovir alafenamide (TAF), which participants in this trial may receive, works well for treating chronic hepatitis B. Earlier studies proved that TAF greatly lowers hepatitis B virus levels in the body, with many patients achieving a full response within 24 weeks. Long-term research has found that TAF effectively keeps the virus under control. These studies also show that TAF is safe and generally well-tolerated, with no resistance developing even after several years of use. This evidence suggests that TAF is a promising option for managing chronic hepatitis B. ^{6 7 8 9 10}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for children and teens with chronic hepatitis B. They must have had the virus for at least 6 months, weigh a minimum of 10 kg (22 lbs), and not be pregnant or breastfeeding. Participants should not have other liver diseases, HIV, HCV, HDV co-infections, cancer history within the last 5 years or substance abuse issues.

Inclusion Criteria

Willing and able to provide written informed consent/assent (child and parent/legal guardian)

Documented evidence of CHB (eg, HBsAg-positive for ≥ 6 months)

Estimated creatinine clearance (CLCr) ≥ 80 mL/min/1.73m^2 (using the Schwartz formula)

Exclusion Criteria

I am not pregnant or breastfeeding.

I am currently on medication that affects my immune system.

Abnormal hematological and biochemical parameters

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAF or placebo for 24 weeks

24 weeks

Weekly visits for PK sampling and monitoring

Open-label extension

Participants may opt into continuation of TAF treatment for an additional 216 weeks

216 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tenofovir Alafenamide (TAF)

Trial Overview The study tests Tenofovir Alafenamide (TAF) against a placebo to see how effective and safe it is in treating young people with chronic hepatitis B. It also aims to find out the right dose levels for children.

How Is the Trial Designed?

Group I: TAF (Cohort 2 Group 3) Experimental Treatment 1 Intervention

Participants (2 to \< 6 years) will receive TAF for 24 weeks as follows: * weight ≥ 10 kg to \< 14 kg (7.5 mg oral granules) * weight ≥ 14 kg to \< 25 kg (15 mg oral granules)

Group II: TAF (Cohort 2 Group 2) Experimental Treatment 1 Intervention

Participants (6 to \< 12 years) weighing ≥ 14 kg to \< 25 kg will receive TAF 15 mg oral granules for 24 weeks

Group III: TAF (Cohort 2 Group 1) Experimental Treatment 1 Intervention

Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks

Group IV: TAF (Cohort 1) Experimental Treatment 1 Intervention

Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks

Group V: Open-Label TAF Experimental Treatment 1 Intervention

Following 24 weeks of blinded randomized treatment, participants will be eligible to participate in an open-label extension phase to receive TAF for an additional 216 weeks.

Group VI: Cohort 2 Placebo Placebo Group 1 Intervention

Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.

Group VII: Placebo (Cohort 1) Placebo Group 1 Intervention

Participants (12 to \< 18 years) weighing ≥ 35 kg will receive placebo tablet for 24 weeks

Tenofovir Alafenamide (TAF) is already approved in United States, European Union for the following indications:

Approved in United States as Vemlidy for:

• Chronic hepatitis B virus (HBV) infection
• HIV-1 infection

Approved in European Union as Vemlidy for:

• Chronic hepatitis B virus (HBV) infection
• HIV-1 infection

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Published Research Related to This Trial

In patients with familial Mediterranean fever (FMF) who do not respond adequately to colchicine (5-10% to 40% non-responder rate), adding thalidomide may enhance control over febrile attacks and the acute phase response.

This case report highlights the potential of thalidomide as an effective adjunct therapy for patients resistant to standard colchicine treatment, suggesting a new avenue for managing FMF symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. Seyahi, E., Ozdogan, H., Masatlioglu, S., et al.[2017]

In a study of 309 FMF patients and 250 healthy controls, specific polymorphisms in the ABCB1 gene were found to be associated with increased susceptibility to Familial Mediterranean fever (FMF), particularly the CT genotype of the C3435T polymorphism and the CT-GT-CT triple genotype.

Conversely, certain genotypes and haplotypes, such as the CT-GG binary genotype and specific haplotypes, were identified as having a protective effect against FMF, suggesting that genetic variations in the ABCB1 gene may influence the risk of developing this disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association analysis of three ABCB1 (MDR1) gene variants (C1236T, G2677A/T and C3435T) and their genotype/haplotype combinations with the familial Mediterranean fever. Rustemoglu, A., Gumus-Akay, G., Karakus, N., et al.[2018]

Familial Mediterranean fever (FMF) is a hereditary autoinflammatory syndrome caused by mutations in the MEFV gene, leading to recurrent fever and potential complications like AA amyloidosis.

Canakinumab, an anti IL-1β antibody, has recently been approved by the FDA as an effective alternative treatment for FMF in patients who do not respond to or cannot tolerate colchicine, significantly improving their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab for the treatment of familial Mediterranean fever. Ozdogan, H., Ugurlu, S.[2019]

In a study of 334 chronic hepatitis B patients in China, Tenofovir alafenamide (TAF) demonstrated similar efficacy to Tenofovir disoproxil fumarate (TDF) in reducing HBV DNA levels after 3 years, with 83% of TAF patients achieving HBV DNA <29 IU/mL compared to 79% for TDF.

TAF showed improved safety profiles, with less decline in kidney function and bone mineral density compared to TDF, indicating it may be a safer option for long-term treatment in chronic hepatitis B patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China. Hou, J., Ning, Q., Duan, Z., et al.[2022]

In a study of 272 patients with hepatitis B virus-related acute-on-chronic liver failure, those treated with tenofovir alafenamide (TAF) had a significantly higher survival rate without transplantation (76%) compared to those treated with entecavir (ETV) (58%) after 48 weeks.

TAF also demonstrated better kidney safety, with a greater improvement in kidney function and a lower risk of chronic kidney disease progression compared to ETV, indicating it may be a safer option for patients with liver failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study. Peng, W., Gu, H., Cheng, D., et al.[2023]

Tenofovir alafenamide (TAF) is effective in suppressing HBV viral load and is noninferior to tenofovir disoproxil fumarate (TDF) over 144 weeks of treatment, making it a suitable option for both treatment-naive and treatment-experienced patients.

TAF has a better safety profile than TDF, showing a reduced risk of nephrotoxicity and less decline in bone mineral density, particularly beneficial for patients with chronic hepatitis B and compensated liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection. Childs-Kean, LM., Egelund, EF., Jourjy, J.[2021]

At 96 weeks, tenofovir alafenamide (TAF) demonstrated similar efficacy to tenofovir disoproxil fumarate (TDF) in suppressing the hepatitis B virus in both HBeAg-positive and HBeAg-negative patients, with viral suppression rates of 73% vs. 75% and 90% vs. 91%, respectively.

TAF showed improved safety profiles compared to TDF, with significantly less impact on bone mineral density and renal function, indicating it may be a safer long-term treatment option for patients with chronic hepatitis B.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. Agarwal, K., Brunetto, M., Seto, WK., et al.[2021]

In a study of 313 chronic hepatitis B patients, switching from entecavir or nucleos(t)ide analogue combination therapy to tenofovir alafenamide (TAF) significantly increased HBV DNA suppression rates from 75.9% to 96.9% after 48 weeks, demonstrating TAF's effectiveness in viral control.

Patients with chronic kidney disease (CKD) who switched to TAF showed significant improvement in renal function, with an increase in estimated glomerular filtration rate (eGFR) compared to those without CKD, indicating TAF's renal safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. Ogawa, E., Nomura, H., Nakamuta, M., et al.[2021]

Tenofovir alafenamide (TAF) is as effective as tenofovir disoproxil fumarate (TDF) in reducing HBV DNA levels in patients with chronic hepatitis B, with no detected resistance through 96 weeks of treatment.

TAF shows improved safety profiles compared to TDF, including a lower impact on kidney function and bone mineral density, along with a higher rate of ALT normalization, suggesting it may be a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. Ogawa, E., Furusyo, N., Nguyen, MH.[2021]

A multidisciplinary panel developed 18 evidence-based recommendations for the treatment and follow-up of Familial Mediterranean fever (FMF), aimed at guiding rheumatologists and health professionals in managing this common autoinflammatory disease.

The recommendations received strong agreement (greater than 7/10) from experts, indicating a consensus on their importance, although some areas, like follow-up and dose adjustments, remain controversial due to limited supporting evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EULAR recommendations for the management of familial Mediterranean fever. Ozen, S., Demirkaya, E., Erer, B., et al.[2022]

In a study of 391 patients with chronic hepatitis B who switched to tenofovir alafenamide (TAF), 99% achieved undetectable HBV DNA levels after 144 weeks, demonstrating TAF's long-term virological effectiveness.

Switching to TAF improved kidney function in patients previously treated with tenofovir disoproxil fumarate (TDF), although there was a notable increase in cholesterol and triglyceride levels, highlighting the need for monitoring lipid levels in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to tenofovir alafenamide for nucleos(t)ide analogue-experienced patients with chronic hepatitis B: week 144 results from a real-world, multi-centre cohort study. Ogawa, E., Nakamuta, M., Koyanagi, T., et al.[2023]

Colchicine taken three times daily may significantly reduce the number of attacks in patients with Familial Mediterranean fever (FMF), although evidence is limited and based on low-certainty studies involving 10 participants.

Canakinumab has shown promise in reducing the frequency of attacks in colchicine-resistant FMF patients, with moderate-certainty evidence from a study of 63 participants, and it also appears to lower inflammatory markers like C-reactive protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for reducing inflammation in familial Mediterranean fever. Yin, X., Tian, F., Wu, B., et al.[2023]

Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in 167 patients with chronic hepatitis B maintained similar rates of complete viral suppression (77.8% vs 76% after 48 weeks), indicating TAF's effective antiviral efficacy.

The study also found that renal function stabilized after switching to TAF, with a decrease in estimated glomerular filtration rate during TDF therapy, while body weight and BMI initially decreased on TDF but returned to baseline levels after switching to TAF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study. Su, PY., Su, WW., Hsu, YC., et al.[2022]

Citations

1. vemlidy.com vemlidy.com/results

Results with VEMLIDY VEMLIDY was shown to reduce the amount of hepatitis B virus in patients. The studies looked at hepatitis B virus levels in the body, which is called HBV DNA ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8845166/

Effectiveness of Tenofovir Alafenamide in Chronic Hepatitis ... CHB patients who had normal ALT and detectable HBV DNA and did not meet “CHB prevention guide (2019)”, could achieve complete virological response in 24 weeks.

3. vemlidyhcp.com vemlidyhcp.com/taf-vs-tdf-virologic-response/

VEMLIDY TAF vs TDF Virologic Response | HCP Site Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: final results from two randomised phase 3 trials.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39327857/

Eight-year efficacy and safety of tenofovir alafenamide for ... Long-term TAF treatment exhibited favourable safety and tolerability with high rates of viral suppression and no development of resistance.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2542568424000618

Long-term efficacy and safety of tenofovir alafenamide, ... A small-sample study comparing the efficacy of TDF and ETV suggested that TDF may outperform ETV in treating HBV-ACLF by rapidly suppressing the virus, ...

6. gilead.com gilead.com/-/media/files/pdfs/medicines/liver-disease/vemlidy/vemlidy_pi.pdf

VEMLIDY® (tenofovir alafenamide) tablets, for oral use Safety and effectiveness of VEMLIDY has not been established in pediatric patients with chronic HBV infection who are less than 6 years of age or weigh less ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11599788/

Eight‐year efficacy and safety of tenofovir alafenamide for ... Eight‐year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/208464s008lbl.pdf

VEMLIDY® (tenofovir alafenamide) - accessdata.fda.gov The safety assessment of VEMLIDY was based on pooled data through the Week 96 data analysis from 1298 subjects in two randomized, double-blind, ...

9. vemlidy.com vemlidy.com/

Chronic Hep B Treatment | VEMLIDY® (tenofovir ... VEMLIDY® is a prescription medication used to treat chronic hepatitis B virus in adults with stable liver disease. See Important Safety Information and

10. vemlidyhcp.com vemlidyhcp.com/clinical-resources/

Clinical Resources for VEMLIDY | HCP Site The following resources provide an overview of VEMLIDY clinical data for healthcare providers managing patients with chronic hepatitis B.