TAF for Chronic Hepatitis B
Recruiting in Palo Alto (17 mi)
+37 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Gilead Sciences
Must not be taking: Immunomodulators, Immunosuppressants
Disqualifiers: Pregnancy, Hepatitis C, HIV, others
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
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.
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.
12345Is 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.
14678How 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.
910111213Eligibility Criteria
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.
+11 more
Exclusion Criteria
I am not pregnant or breastfeeding.
Abnormal hematological and biochemical parameters
I am currently on medication that affects my immune system.
+9 more
Trial Timeline
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
Participant Groups
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.
7Treatment groups
Experimental Treatment
Placebo Group
Group I: TAF (Cohort 2 Group 3)Experimental Treatment1 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 Treatment1 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 Treatment1 Intervention
Participants (6 to \< 12 years) weighing ≥ 25 kg will receive TAF 25 mg tablet for 24 weeks
Group IV: TAF (Cohort 1)Experimental Treatment1 Intervention
Participants (12 to \< 18 years) weighing ≥ 35 kg will receive TAF 25 mg tablet for 24 weeks
Group V: Open-Label TAFExperimental Treatment1 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 PlaceboPlacebo Group1 Intervention
Participants will receive matching placebo of TAF (tablet or oral granules) for 24 weeks.
Group VII: Placebo (Cohort 1)Placebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nationwide Children's HospitalColumbus, OH
Johns Hopkins UniversityBaltimore, MD
Monroe Carell Jr. Children's Hospital at VanderbiltNashville, TN
Texas Children's Hospital - Main HospitalHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Gilead SciencesLead Sponsor
References
96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. [2021]Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials.
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]Tenofovir alafenamide (TAF) may be preferable to other nucleos(t)ide analogues (NA) regarding outcomes against chronic hepatitis B virus (HBV) infection.
3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China. [2022]Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).
Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. [2021]Tenofovir alafenamide (TAF) has been newly approved for the treatment of chronic hepatitis B (CHB). We aimed to assess the effectiveness and renal safety of switching from entecavir (ETV) or nucleos(t)ide analogue (NA) combination therapy to TAF.
Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy. [2021]Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has been approved for the treatment of chronic hepatitis B virus (HBV) infection. TAF has been shown to be a potent inhibitor of HBV replication at a low dose, with high intracellular concentration and more than 90% lower systemic TFV concentration than tenofovir disoproxil fumarate (TDF). In two randomized, double-blind, multinational, Phase 3, non-inferiority trials for hepatitis B e antigen (HBeAg)-positive and -negative patients (primary analysis: 48 weeks), TAF 25 mg orally once-daily was not inferior to TDF 300 mg in achieving an HBV DNA level
Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study. [2023]Real-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population.
Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection. [2021]Tenofovir alafenamide (TAF) is indicated for adult patients with chronic hepatitis B virus (HBV) infection with compensated liver disease at an oral dose of 25 mg/day. TAF is a more stable prodrug in the plasma than tenofovir disoproxil fumarate (TDF), leading to decreased plasma exposure of tenofovir. Decreased exposure is thought to reduce the risk of long-term TDF toxicities, such as nephrotoxicity and decreased bone mineral density (BMD). TAF, a nucleotide reverse transcriptase inhibitor, has the same mechanism of action as TDF. The results of phase III primary trials and extensions showed that TAF is noninferior to TDF at suppressing the HBV viral load in treatment-naive and treatment-experienced HBeAg-negative and HBeAg-positive patients at 48 weeks, 96 weeks, and 144 weeks of therapy. The most commonly reported adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. At all evaluated time points (out to 144 wks of treatment), patients who received TAF had less risk of nephrotoxicity and less of a decline in BMD than the patients who received TDF. TAF appears to be safe in patients with a creatinine clearance (Clcr ) above 15 ml/min; however, TAF is not currently recommended in patients with an estimated Clcr below this threshold. TAF is safe in patients with mild hepatic impairment but is not currently recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).
Real-world experience of switching from tenofovir disoproxil fumarate to tenofovir alafenamide in patients with chronic hepatitis B: a retrospective study. [2022]Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited.
Successful treatment of familial Mediterranean fever attacks with thalidomide in a colchicine resistant patient. [2017]Colchicine is the treatment of choice in familial Mediterranean fever (FMF) both for attacks and for prevention of secondary amyloidosis. The overall non-responder rate varies from 5-10 to 40%. Thalidomide is known to blunt the acute phase response. We report the efficacy of the addition of thalidomide to colchicine in controlling the febrile attacks and acute phase response in a patient with FMF resistant to 2 mg colchicine per day.
Association analysis of three ABCB1 (MDR1) gene variants (C1236T, G2677A/T and C3435T) and their genotype/haplotype combinations with the familial Mediterranean fever. [2018]1. Familial Mediterranean fever (FMF) is considered an autosomal recessive disorder, associated with a single gene named Mediterranean fever (MEFV). The aim of this study was to perform genotyping and haplotyping analysis of the multidrug resistance (ATP-binding cassette, subfamily B, member 1 - ABCB1) gene in FMF patients. 2. Three ABCB1 gene polymorphisms (C1236T, G2677T/A and C3435T) were analyzed in 309 FMF patients and 250 healthy control subjects. All subjects were genotyped by PCR-restriction fragment length polymorphism analysis, and statistical analysis was performed using the Arlequin 3.1.1 and SPSS 16.0 software packages. 3. The CT genotype frequency of the C3435T polymorphism (p = 0.003), the CT-GT-CT (C1236T-G2677T/A-C3435T) triple genotype (p = 0.001) and the C-G (C1236T-G2677T/A) haplotype (p = 0.030) were more common in the FMF patients. The CT-GG-CC triple genotype and T-G-C, C-T-T and T-G-T haplotypes (C1236T-G2677T/A-C3435T) were higher in the control subjects (p = 0.011, 0.001, 0.009 and 0.000, respectively). The CT-GG binary genotype and C-T and T-G haplotypes for C1236T-G2677T/A polymorphisms may have a high degree of protective effect against FMF (p = 0.0005, 0.002 and 0.000, respectively). 4. Our study showed that genotypes and haplotypes of ABCB1 gene polymorphisms may affect patients' FMF susceptibility.
EULAR recommendations for the management of familial Mediterranean fever. [2022]Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0-10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF.
Interventions for reducing inflammation in familial Mediterranean fever. [2023]Familial Mediterranean fever (FMF), a hereditary auto-inflammatory disease, mainly affects ethnic groups living in the Mediterranean region. Early studies reported colchicine may potentially prevent FMF attacks. For people who are colchicine-resistant or intolerant, drugs such as anakinra, rilonacept, canakinumab, etanercept, infliximab or adalimumab might be beneficial. This is an update of the review last published in 2018.
Canakinumab for the treatment of familial Mediterranean fever. [2019]Familial Mediterranean fever (FMF) is the most frequent of all hereditary autoinflammatory syndromes. It is characterized by recurrent attacks of fever and serositis. If not treated it may be complicated with AA amyloidosis. It is caused by mutations in the MEFV gene that encodes pyrin which is involved in the regulation of IL-1β. The mainstay of treatment is colchicine, however a subset of patients requires an alternative treatment either due to inadequate response or intolerance. The accumulating data indicates that anti IL-1 drugs are effective in treating colchicine resistant FMF cases and improving their quality of life. Areas covered: This review focuses on canakinumab, a fully human anti IL-1β antibody, treatment in FMF. Expert commentary: Canakinumab became the first approved therapy by the Food and Drug Administration for FMF very recently, which highlights its importance as the alternative treatment in FMF.