TAF for Chronic Hepatitis B

Recruiting at 30 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

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goals of this clinical study are to compare the effectiveness, safety and tolerability of study drug, tenofovir alafenamide (TAF), versus placebo in teens and children with CHB and to learn more about the dosing levels in children.

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 Tenofovir Alafenamide (TAF) safe for humans?

Tenofovir Alafenamide (TAF) is generally considered safe for humans, with studies showing it has fewer kidney and bone side effects compared to a similar drug, Tenofovir Disoproxil Fumarate (TDF). Common side effects include headache, abdominal pain, fatigue, cough, nausea, and back pain, and it is not recommended for people with severe liver or kidney issues. ^{1 2 3 4 5}

How does the drug Tenofovir Alafenamide (TAF) differ from other treatments for chronic Hepatitis B?

Tenofovir Alafenamide (TAF) is unique because it is a prodrug, meaning it is converted into its active form inside the body, allowing for lower doses and potentially fewer side effects compared to other treatments for chronic Hepatitis B. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Tenofovir Alafenamide (TAF) for treating chronic hepatitis B?

Research shows that Tenofovir Alafenamide (TAF) is effective in treating chronic hepatitis B, with similar efficacy to Tenofovir Disoproxil Fumarate (TDF) but with better kidney and bone safety. Studies have demonstrated that TAF efficiently delivers the active ingredient to the liver, where it is needed, while maintaining lower levels in the bloodstream, reducing potential side effects. ^{3 4 11 12 13}

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)

I am a man or a woman not pregnant or breastfeeding.

My weight is between 30 lbs and 55 lbs.

Exclusion Criteria

I am not pregnant or breastfeeding.

Abnormal hematological and biochemical parameters

I am currently on medication that affects my immune system.

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

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 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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. [2021]

2. England 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection. [2021]

8. United States 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. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. [2017]

10. England 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. [2018]

11. England pubmed.ncbi.nlm.nih.gov

EULAR recommendations for the management of familial Mediterranean fever. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Interventions for reducing inflammation in familial Mediterranean fever. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Canakinumab for the treatment of familial Mediterranean fever. [2019]