Tenofovir Alafenamide in HBV Related Decompensated Liver

NCT ID: NCT04683341

Last Updated: 2020-12-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2025-04-01

Brief Summary

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.

Conditions

HBV

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - initial TAF treatment group

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.

Group Type: EXPERIMENTAL

Tenofovir Alafenamide Tablets

Intervention Type: DRUG

Approximately 100 adults, cirrhotic or non-cirrhotic (capped at 50), CHB patients with hepatic decompensation, will receive initial treatment (Arm A) with or switch (Arm B) to TAF 25 mg/day for 144 weeks. For Initiation Arm (Arm A), CHB patients with hepatic decompensation, who are currently not under HBV antiviral treatment will be enrolled. For Switch Arm (Arm B), CHB patients who are currently with hepatic decompensation and virally suppressed under HBV NUC treatment (HBV DNA \< 20 IU/mL) will be enrolled.

Arm B - switch to TAF treatment group

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

Group Type: EXPERIMENTAL

Tenofovir Alafenamide Tablets

Intervention Type: DRUG

Approximately 100 adults, cirrhotic or non-cirrhotic (capped at 50), CHB patients with hepatic decompensation, will receive initial treatment (Arm A) with or switch (Arm B) to TAF 25 mg/day for 144 weeks. For Initiation Arm (Arm A), CHB patients with hepatic decompensation, who are currently not under HBV antiviral treatment will be enrolled. For Switch Arm (Arm B), CHB patients who are currently with hepatic decompensation and virally suppressed under HBV NUC treatment (HBV DNA \< 20 IU/mL) will be enrolled.

Interventions

Tenofovir Alafenamide Tablets

Approximately 100 adults, cirrhotic or non-cirrhotic (capped at 50), CHB patients with hepatic decompensation, will receive initial treatment (Arm A) with or switch (Arm B) to TAF 25 mg/day for 144 weeks. For Initiation Arm (Arm A), CHB patients with hepatic decompensation, who are currently not under HBV antiviral treatment will be enrolled. For Switch Arm (Arm B), CHB patients who are currently with hepatic decompensation and virally suppressed under HBV NUC treatment (HBV DNA \< 20 IU/mL) will be enrolled.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ming-Lung Yu, Professor

Role: PRINCIPAL_INVESTIGATOR

Hepatobiliary Division, Kaohsiung Medical University Hospital

Locations

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ming-Lung Yu, Professor

Role: CONTACT

Phone: 886-7-3121101

Email: fish6069@gmail.com

Facility Contacts

Ming-Lung Yu

Role: primary

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Other Identifiers

TAF-Deliver

Identifier Type: -

Identifier Source: org_study_id