Safety and Efficacy of Therapeutic Hepatitis B Adenovirus Injection (T101) in Chronic Hepatitis B Patients

NCT04168333 | Completed Phase 1

• 1 other identifier: TC-2017-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatitis B virus (HBV) infection is a worldwide health problem. It has been proved that the persistence of HBV is associated with the failure to stimulate an efficient HBV-specific immune response. T101, the Chinese counterpart of TG1050, is a replication-defective adenovirus serotype 5 (Ad5) expressing multiple HBV-specific antigens (core, polymerase and envelope) and is used as therapeutic vaccine for chronic hepatitis B patients. The application of T101 aims at inducing a broad HBV-specific cellular immune response and ultimately eliminating HBV infection.

Conditions

Hepatitis B Virus (HBV)

Keywords

Hepatitis B virus (HBV) infection

Outcome Measures

Primary Outcomes (6)

• Adverse events

  Observe all the adverse events of all patients, record their clinical features, severity, time of occurence, end time, duration, treatment measures, recovery and determine their correlation with T101

  through study completion, an average of 1 year

• Vital signs index

  vital signs measure: include body temperature, pulse rate, respiratory rate and blood pressure, to observe whether there are abnormal index, especially whether there are abnormal index caused by acute allergic reaction.

  Single Dose Group: baseline, Day-1, Day1, Day8, Day15, Day2ine9; Multiple Dose Group: baseline, Day-1, Day7, Day8, Day14, Day15, Day22, Day29, Day43, Day71, Day99.

• Routine blood test

  Observe the blood routine tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.

  Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.

• Blood biochemical test

  Observe the blood biochemical tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.

  Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.

• Coagulation function test

  Observe the coagulation function tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.

  Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.

• Routine urinalysis

  Observe the routine urinalysis tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.

  Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.

Secondary Outcomes (4)

• HBsAg quantitative levels

  Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.

• HBeAg quantitative levels

  Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.

• Ad5 neutralizing antibodies

  Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.

• Cellular and humoral immune responses

  Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.

Study Arms (2)

T101 Group

ACTIVE COMPARATOR

The study will consist of 2 cohorts: Single Dose (SD) Cohort: 9 chronic hepatitis B patients will be enrolled and be divided into 3 groups, with 3 patients in each group. Multiple Dose (MD) Cohort: 18 chronic hepatitis B patients will be enrolled and be divided into 2 groups, with 9 patients in each group.

Biological: T101 Group

Placebo Group

PLACEBO COMPARATOR

The study will consist of 2 cohorts: Single Dose (SD) Cohort: 3 chronic hepatitis B patients will be enrolled in this group. Multiple Dose (MD) Cohort: 6 chronic hepatitis B patients will be enrolled in this group.

Biological: Placebo Group

Interventions

T101 Group BIOLOGICAL

Single Dose (SD) Cohort: In each group, 3 of chronic hepatitis B patients will be subcutaneously injected with different dose level of T101 at 1.0E+9VP (Group1)/1.0E+10VP (Group2)/1.0E+11VP (Group 3) on D1. Multiple Dose (MD) Cohort: In each group, 9 of chronic hepatitis B patients will be subcutaneously injected with different dose level of T101 at 1.0E+10VP (Group1)/1.0E+11VP (Group2) on D1, D8, D15.

T101 Group

Placebo Group BIOLOGICAL

Single Dose (SD) Cohort: 3 of chronic hepatitis B patients will be subcutaneously injected with placebo on D1. Multiple Dose (MD) Cohort: 6 of chronic hepatitis B patients will be subcutaneously injected with placebo on D1, D8, D15.

Placebo Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Signed, written Independent Ethics Committee (IEC)-approved informed consent.
• \) Patients can cooperate to finish the trial in accordance with the requirements of protocol.
• ）Patients (including partners) are willing to have no pregnancy program and take effective contraceptive measures voluntarily from the initiation of trial to 6 months after the last administration.
• \) 18 through 65 years of age, inclusive.
• ）Body weight is no less than 50 kg for male or no less than 45 kg for female and body mass index(BMI) must be within the range of 18-30kg/m2.
• ）Compensated liver disease; defined as total bilirubin ≤2 × ULN, PT ≤ 1.2 ×ULN, platelets ≥100,000/mm3(100\*109/L), serum albumin ≥35 g/L, and no prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, variceal hemorrhage).
• \) Patients must be receiving antiviral treatment with nucleoside analog and have negative HBV DNA(defined HBV DNA \<20 IU/Ml).
• \) Chronic hepatitis B patients have positive HBsAg.
• \) ALT ≤ 1.5×ULN.
• \) Haemoglobin ≥ 10 g/L
• \) Creatinine clearance \> 50mL/min.
• \) Neutrophils ≥1,200/mm3(1.2\*109/L).
• \) FibroScan score ≤ 17.5 kPa within 6 months prior to screening or during screening, or proven not to have cirrhosis according to liver tissues within 12 months.

You may not qualify if:

• \) Addicted to smoking (\>5 cigarettes per day) for 3 months prior to the initiation of trial.
• \) Subjects susceptible to allergies, including a history of allergy to investigational medical product (IMP) or its buffer.
• \) History of drug abuse and/or alcohol abuse(≥14 units of alcohol per week; 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine).
• \) Patients who have donated or lost an amount of blood\> 450ml within 3 months prior to the screening of the trial.
• \) Patients who are positive urine test of drug on screening or a history of drug abuse or use of narcotic drugs during the past five years.
• \) Patients who have used any drug that can alter the enzyme activity of liver within 28 days prior to screening.
• \) Patients who have taken any prescription, nonprescription, vitamin product or herbal medicine within 14 days prior to the screening(except for nucleoside analogues).
• \) Patients who have taken a special diet (including dragon fruit, mango, grapefruit, etc.) within 2 weeks prior to screening, or have strenuous exercise, or other factors that affect drug absorption, distribution, metabolism and excretion.
• \) Patients who are taking inhibitors or inducers of CYP3A4, P-gp or Bcrp such as itraconazole, ketoconazole or dronedarone.
• \) Patients who have significant changes in diet or exercise habit.
• \) Patients who have participated in any clinical trial or taken any IMP within 3 months prior to the trial.
• \) Patients with an clinically significant and abnormal ECG.
• \) Female patients who are pregnant, breast-feeding or positive result of pregnancy test.
• \) Patients with abnormal laboratory test results that have clinically significant or clinically significant disease(including but not limited to the gastrointestinal tract, kidney, liver, neurological, haematological, endocrine, lung, immune, mental or cardiovascular disease).
• \) Patients with α-fetoprotein \> 50 ng/Ml.

Sponsors & Collaborators

• Tasly Tianjin Biopharmaceutical Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, China

Location

MeSH Terms

Conditions

Hepatitis B; Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2019
• First Posted: November 19, 2019
• Study Start: January 8, 2018
• Primary Completion: October 14, 2019
• Study Completion: October 14, 2019
• Last Updated: December 4, 2019

Record last verified: 2019-12

Locations

CN (1)