Tenofovir Alafenamide in HBV Related Decompensated Liver

Kaohsiung Medical University

Status and phase: Enrolling; Phase 4

Conditions: HBV

Treatments: Drug: Tenofovir Alafenamide Tablets

Study type: Interventional

Funder types: Other

Identifiers

NCT04683341

TAF-Deliver

Details and patient eligibility

About

TAF is a new prodrug of tenofovir, specifically designed to achieve higher intracellular active drug concentration allowing for dosing of only 25 mg once daily and thus can potentially lower the already relatively low risk of renal toxicity and bone loss with TDF. However, such renal and bone complications with TDF may become more pronounced in decompensated CHB patients10. In the phase 3 trials11, 12, TAF had demonstrated a compatible antiviral effect (noninferior efficacy), and a higher rate of alanine aminotransferase (ALT) normalization to TDF. TAF also demonstrated an improved renal function and less bone loss compared to TDF. Therefore, TAF was approved as the first line therapy for CHB patients with compensated liver function. The lack of data regarding TAF therapy in decompensated CHB patients raised the concern of safety and efficacy of TAF in this group of patients. A small, single arm Phase 2 switch study (GS-US-320-4035; Study 4035; NCT03180619) which has enrolled 31 subjects with CPT scores ≥7, either at time of screening or by history, who were virally suppressed on TDF and/or other oral antiviral agents is currently underway with favorable safety and efficacy results through 48 weeks.[Lim YS, Lin CY, Heo J, et al. EASL 2020, poster SAT442.] While Gilead Study 4035 will continue through 96 weeks of treatment, additional data in this population are thus needed, particularly in CHB patients who have decompensated liver disease and are not being treated and are viremic. Herein, we conduct the present study and aim to investigate the safety and efficacy of TAF in CHB patients with hepatic decompensation.

Enrollment: 100 estimated patients

Sex: All

Ages: 20 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or non-pregnant female, age ≥20 years
• Chronic HBV infection with positive hepatitis B surface antigen (HBsAg) for at least 6 months at screening.
• Hepatic decompensation, defined as Child-Turcotte-Pugh (CTP) score ≥7, or the presence of portal hypertension related complications including ascites, hepatic encephalopathy (<grade 2) at screening.
• HBV NUC treatment naïve or experienced (except prior TAF) for Arm A or currently under HBV NUC treatment (except TAF) with HBV DNA < 20 IU/mL within 6 months prior screening for Arm B.
• Patients with either liver cirrhosis or non-cirrhosis (defined by histology, non-invasive assessments, or imaging/clinical based diagnosis).
• Estimated creatinine clearance ≥30 ml/min (using the Cockcroft-Gault method) at screening. (Note: multiply estimated rate by 0.85 for women).
• Willing and able to provide informed consent
• Able to comply with dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion criteria

• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study.
• Previous recipient of a solid organ (including liver), or bone marrow transplant.
• Severe or uncontrolled comorbidities determined by the Investigator.
• Currently ≥grade 2 hepatic encephalopathy, currently or history (within 60 days) of variceal bleeding, hepatorenal syndrome, refractory ascites or spontaneous bacterial peritonitis; cytopenia of absolute neutrophil count < 750/mm3, or hemoglobin < 8 g/dL, or platelet <30000/mm3; or MELD score ≥30 at screening.
• Malignancy history including hepatocellular carcinoma, except basal cell skin cancer without recurrence for more than 5 years.
• Acute exacerbation of HBV, defined as an elevation of alanine aminotransferase (ALT) activity to more than 10 times the upper limit of normal and more than twice the baseline value.
• On any of the disallowed concomitant medications listed in the prior and concomitant medications list (pg. 16). Subjects on prohibited medications who are otherwise eligible will need a wash out period of at least 30 days prior to the Screening.
• Males and females of reproductive potential who are unwilling to use "effective" protocol-specified method(s) of contraception during the study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Arm A - initial TAF treatment group

Experimental group

Description:

cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and HBV NUC treatment naïve or experienced (except prior TAF) will receive initial treatment (Arm A) with TAF 25 mg/day.

Treatment:

Drug: Tenofovir Alafenamide Tablets

Arm B - switch to TAF treatment group

Experimental group

Description:

cirrhotic or non-cirrhotic CHB patients with hepatic decompensation and currently under HBV NUC treatment (except TAF) with HBV DNA \< 20 IU/mL within 6 months prior screening will switch (Arm B) to TAF 25 mg/day

Treatment:

Drug: Tenofovir Alafenamide Tablets