A Perspective Study of the Antiviral Efficacy and Safety of Switching to TAF Treatment in CHB Adults With Suboptimal Response (SOR) and Intolerant to Entecavir

A Perspective Study of the Antiviral Efficacy and Safety of Switching to TAF Treatment in CHB Adults With Suboptimal Response (SOR) or Intolerant to Entecavir

This is a multicenter, single arm, open label, historical control pilot Study to the antiviral efficacy and safety of Suboptimal Responders to Entecavir Switching to TAF Treatment at week 48 (investigate the rates of complete virological response on switching to TAF in patients with Suboptimal response or ETV intolerance to standard ETV= 0.5 mg monotherapy).

Study Overview

• Status: Unknown
• Conditions: HBV
• Intervention / Treatment: Drug: Tenofovir Alafenamide (TAF)

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures;
2. Male and female subjects,18 years of age and older, based on the date of the screening visit;
3. Suboptimal Responders to Entecavir (defined as CHB patients treated with at least 12 months of ETV 0.5mg QD with prior suboptimal response viral load still detectable at week 48).
4. ETV intolerance population (defined as unwilling or poor adherence to administer ETV in fasting food, renal impairment with ETV dosage adjustment required, pts with other unidentified reasons willing to switch, etc);
5. Screening serum ALT level ≤ 10 × ULN;
6. Normal ECG (or if abnormal, determined by the Investigator not to be clinically significant);
7. Must be willing and able to comply with all study requirements.

Exclusion Criteria:

1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study;
2. Co-infection with HCV, HIV, or HDV;
3. Any history of, or current evidence of, clinical hepatic decompensation (i.e., moderate-severe ascites, encephalopathy or variceal hemorrhage);
4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging);
5. Abnormal hematological and biochemical parameters, including: Hemoglobin < 10 g/dl, Absolute neutrophil count < 0.75×109/L, Platelets ≤ 50×109/L, AST or ALT > 10 × ULN, Total bilirubin > 2.5 × ULN, Albumin < 3.0 g/dl, INR > 1.5 × ULN;
6. Received solid organ or bone marrow transplant;
7. Recent history of pancreatitis (within 24 weeks prior to the first dose of study medication);
8. Evidence of other autoimmune or metabolic liver diseases (except non-alcoholic fatty liver disease);
9. Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the investigator;
10. Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection(basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible;
11. Known hypersensitivity to study drugs, metabolites, or formulation excipients;
12. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance;
13. Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental Arm; Tenofovir alafenamide (TAF) 25 mg QD, oral administration, 48 weeks；	Drug: Tenofovir Alafenamide (TAF); Tenofovir alafenamide (TAF) 25 mg QD, oral administration, 48 weeks；

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main efficacy endpoint	The primary efficacy endpoint is the proportion of subjects with plasma HBV DNA levels below 20 IU/ml at Week 48.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary efficacy endpoint	The proportion of subjects with plasma HBV DNA < 20 IU/mL at Weeks 24	Week 24
Key secondary efficacy endpoint	The change from baseline in plasma HBV DNA levels at Weeks 48	Week 48
Key secondary efficacy endpoint	The proportion of subjects with ALT normalization at Weeks 24 and 48	Week 24 and Week 48
Key secondary efficacy endpoint	The proportion of subjects with HBeAg seroconversion to anti-HBe at Weeks 48	Week 48
Key secondary efficacy endpoint	The HBV DNA maintenance rate at week 48 in ETV intolerant pts.	Week 48
Key secondary efficacy endpoint	The proportion of subjects with HBsAg seroconversion to anti-HBs at Weeks 48	Week 48
Key secondary efficacy endpoint	The incidence of drug resistant mutations at Weeks 48	Week 48

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2019
• Primary Completion (ANTICIPATED): June 1, 2021
• Study Completion (ANTICIPATED): June 1, 2021

Study Registration Dates

• First Submitted: July 24, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (ACTUAL): July 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: ISR-CN-18-10478

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes