Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04683341




Registration number
NCT04683341
Ethics application status
Date submitted
12/11/2020
Date registered
24/12/2020
Date last updated
24/12/2020

Titles & IDs
Public title
Tenofovir Alafenamide in HBV Related Decompensated Liver
Scientific title
Safety and Efficacy of Tenofovir Alafenamide for Chronic Hepatitis B Patients With Decompensated Liver Disease
Secondary ID [1] 0 0
TAF-Deliver
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HBV 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: 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.

Experimental: Experimental: SHR8735 cohort 3 - The subjects will receive a single dose of SHR8735 (high dose).

Experimental: 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
Comparator / control treatment
Control group

Outcomes

Eligibility
Key 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
Minimum age
20 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2025
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Other
Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04683341
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Ming-Lung Yu, Professor
Address 0 0
Hepatobiliary Division, Kaohsiung Medical University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Ming-Lung Yu, Professor
Address 0 0
Country 0 0
Phone 0 0
886-7-3121101
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04683341