Safety and Efficacy of Therapeutic Hepatitis B Adenovirus Injection (T101) Combined With Nucleoside (Acid) Analogues in Chronic Hepatitis B Patients

A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Therapeutic Hepatitis B Adenovirus Injection (T101) Combined With Nucleoside (Acid) Analogues in Chronic Hepatitis B Patients

A multi-center, randomized, open-label, group controlled study to evaluate the safety and efficacy of T101 combined with nucleoside (acid) analogues in chronic hepatitis B patients.

Study Overview

• Status: Unknown
• Conditions: Hepatitis B Virus (HBV)
• Intervention / Treatment: Biological: ETV/TDF+T101 No.1; Biological: ETV/TDF+T101 No.2; Biological: ETV or TDF; Biological: ETV/TDF+Peg-IFNα-2b

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital,Capital Medical University
    • Beijing, Beijing, China
      • Beijing Ditan Hospital Capital Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300150
      • Tianjin Second People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients must meet all the following inclusion criteria to be enrolled in this study:

• 1. Patients between the ages of 18 and 60 years, male or female;
• 2. Body weight is no less than 45kg for female and no less than 50kg for male;
• 3. Meets the diagnosis and treatment standards of chronic hepatitis B in China's 2015 Guidelines for the Prevention and Treatment of Chronic Hepatitis B;
• 4. Currently, should have taken nucleoside (acid) analogues for 1 year or more;
• 5. HBV DNA<100 IU/ml; HBsAg is positive and no more than 3000 IU/ml；HBeAg is negative；
• 6. Be able to understand and sign informed consent.

Exclusion Criteria:

Patients with any of the following items will not be enrolled in this study:

• 1. Pregnant or lactating women; male or female who have planned to have children from the start of the study to sixth month after the end of the study.
• 2. Have received interferon treatment within 6 months prior to the screening;
• 3. Have taken strong immunomodulators (such as adrenocortical hormone, thymosin alpha 1, thymosin 5, etc.) within 6 months before the screening, and the course of treatment was more than 2 weeks;
• 4. Have taken hepatotoxic drugs (such as dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) within 6 months before screening, and the course of treatment was more than 2 weeks;
• 5. Currently or previously diagnosed or suspected with cirrhosis or liver cancer; or AFP > 50ng/ml;
• 6. Liver diseases caused by other causes: including alcoholic hepatitis, drug hepatitis, autoimmune liver disease;
• 7. Currently be infected of HAV, HCV, HDV, HEV, HIV and syphilis;
• 8. Have mental diseases, including but not limited to depression, anxiety, mania, schizophrenia;
• 9. Uncontrolled epilepsy;
• 10. Complicated with serious systemic diseases, including but not limited to: autoimmune diseases (such as psoriasis, systemic lupus erythematosus, etc.); not well controlled cardiovascular disease (such as high blood pressure, unstable angina pectoris, heart failure, etc.), endocrine system disease (such as thyroid function hyperfunction or loss, diabetes, etc.), respiratory system diseases (such as pulmonary infection, chronic obstructive pulmonary disease and pulmonary interstitial diseases, etc.), digestive system diseases (e.g., chronic colitis, etc.), kidney disease (such as chronic kidney disease, renal insufficiency, etc.), blood system diseases (such as autoimmune anemia, hemophilia, etc.); currently or previously diagnosed or suspected with malignant tumor;
• 11. Fundus diseases, such as not well controlled retinopathy, etc.;
• 12. Laboratory neutrophil count<1.5×109/L; platelet count <90×109/L;
• 13. Prothrombin time was extended by more than 3 seconds compared with the upper limit of normal reference value (ULN);
• 14. ALT>1.5×ULN; TBIL>2×ULN; SCR>1.5×ULN; serum creatine kinase >3×ULN; ALB<35g/L;
• 15. ANA>1:1000, anti-smooth muscle antibody>1:1000, thyrotropic hormone receptor antibody >2×ULN;
• 16. Allergic constitution or allergic to experimental drugs and excipients;
• 17. Plan to receive or have already had an organ transplant;
• 18. Participated in any clinical trial or taken any IMP (investigational medical product) within 3 months prior to the trial;
• 19. Other cases that could not be enrolled in the judgement of the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group1; T101+ETV(Entecavir) /TDF(Tenofovir)	Biological: ETV/TDF+T101 No.1; Patients will be injected with T101 once on Day1 (Week0), Day8 (Week1), Day15 (Week2), Day106 (Week15), Day113 (Week16), Day120 (Week17), Day211 (Week30), Day218 (Week31), Day225 (Week32), Day316 (Week45), Day323 (Week46), Day330 (Week47); ETV or TDF will be administrated once each day successively until Day420.
Active Comparator: Group2; T101+ETV/TDF	Biological: ETV/TDF+T101 No.2; Patients will be injected with T101 once on Day1 (Week0), Day106 (Week15), Day211 (Week30), Day316 (Week45); ETV or TDF will be administrated once each day successively until Day420.
Active Comparator: Group3; ETV or TDF	Biological: ETV or TDF; Patients will be administrated ETV or TDF once each day successively until Day420.
Active Comparator: Group4; Peg-IFNα-2b+ETV/TDF	Biological: ETV/TDF+Peg-IFNα-2b; Patients will be administrated Peg-IFNα-2b successively once a week until Day330 (Week47); ETV or TDF will be administrated once each day successively until Day420.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All the observed or reported AEs (adverse events)	observe and record all the AEs of patients during the clinical trial and determine their correlation with the investigational medical product	through study completion, an average of 60 weeks
HBsAg change	evaluate the HBsAg change from the baseline to evaluate the efficacy of T101	Day106 (Week15), Day211 (Week30), Day316 (Week45), Day337 (Week48), Day421 (Week60) after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of Subjects' HBsAg decrease ≥ 1 log	to evaluate the efficacy of T101	Day106 (Week15), Day211 (Week30), Day316 (Week45), Day337 (Week48), Day421 (Week60) after administration
The percentage of Subjects' HBsAg decrease ≥ 0.5 log	to evaluate the efficacy of T101	Day106 (Week15), Day211 (Week30), Day316 (Week45), Day337 (Week48), Day421 (Week60) after administration
Negative convention rate of HBsAg	to evaluate the efficacy of T101	Day316 (Week45), Day337 (Week48), Day421 (Week60) after administration
Positive convention rate of HBsAb	to evaluate the efficacy of T101	Day316 (Week45), Day337 (Week48), Day421 (Week60) after administration

Collaborators and Investigators

• Sponsor: Tasly Tianjin Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Anticipated): June 30, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: November 3, 2019
• First Submitted That Met QC Criteria: December 4, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): February 8, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Hepatitis B Virus (HBV) infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2b
• Other Study ID Numbers: TSL-BM-T101-II

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No