Hepatitis B Virus (HBV)Phase 1NCT04168333
Safety and Efficacy of Therapeutic Hepatitis B Adenovirus Injection (T101) in Chronic Hepatitis B Patients
A Phase 1 study testing T101 Group in people with Hepatitis B Virus (HBV), run by Tasly Tianjin Biopharmaceutical Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B Virus (HBV)
- What is being tested?
- T101 Group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- 8 Jan 2018to 14 Oct 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1) Signed, written Independent Ethics Committee (IEC)-approved informed consent.
- 2) Patients can cooperate to finish the trial in accordance with the requirements of protocol.
- 3）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.
- 4) 18 through 65 years of age, inclusive.
- 5）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.
- 6）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).
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- 7) Patients must be receiving antiviral treatment with nucleoside analog and have negative HBV DNA(defined HBV DNA <20 IU/Ml).
- 8) Chronic hepatitis B patients have positive HBsAg.
- 9) ALT ≤ 1.5×ULN.
- 10) Haemoglobin ≥ 10 g/L
- 11) Creatinine clearance > 50mL/min.
- 12) Neutrophils ≥1,200/mm3(1.2*109/L).
- 13) 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.
Who cannot join
- 1) Addicted to smoking (>5 cigarettes per day) for 3 months prior to the initiation of trial.
- 2) Subjects susceptible to allergies, including a history of allergy to investigational medical product (IMP) or its buffer.
- 3) 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).
- 4) Patients who have donated or lost an amount of blood> 450ml within 3 months prior to the screening of the trial.
- 5) 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.
- 6) Patients who have used any drug that can alter the enzyme activity of liver within 28 days prior to screening.
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- 7) Patients who have taken any prescription, nonprescription, vitamin product or herbal medicine within 14 days prior to the screening(except for nucleoside analogues).
- 8) 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.
- 9) Patients who are taking inhibitors or inducers of CYP3A4, P-gp or Bcrp such as itraconazole, ketoconazole or dronedarone.
- 10) Patients who have significant changes in diet or exercise habit.
- 11) Patients who have participated in any clinical trial or taken any IMP within 3 months prior to the trial.
- 12) Patients with an clinically significant and abnormal ECG.
- 13) Female patients who are pregnant, breast-feeding or positive result of pregnancy test.
- 14) 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).
- 15) Patients with α-fetoprotein > 50 ng/Ml.
- 16) Patients with positive hepatitis C antibody, HIV antibody, or Treponema pallidum antibody on screening.
- 17) Patients who could not be enrolled in the judgement of the investigators.
- 18) Patients with acute disease or accompanied medication on screening.
- 19) Patients who have taken chocolate or any food and drink that are rich in caffeine or xanthine within 48 hours prior to the administration of IMP.
- 20) Patients who have taken any alcohol product within 24 hours prior to the administration of IMP.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single Center, Randomized, Double-blind, Placebo Controlled, Single Dose (SD) and Multiple Dose (MD), Dose-escalation Clinical Trial to Evaluate the Tolerability and Preliminary Antiviral Activity of Therapeutic Hepatitis B Adenovirus Injection (T101) in Chronic Hepatitis B Patients
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.
Read the detailed description
This study is a randomized, double-blind, placebo-controlled, single dose (SD) and multiple dose (MD) administration study.
Primary Objective: Safety and tolerability;
Secondary Objective:
- Antiviral activity of T101 (HBsAg levels).
- Cellular (HBV-specific) and humoral (AD5 neutralizing antibodies, NAd5) immune responses to T101.
Key Inclusion Criteria:
- Chronic hepatitis B patients with positive HBsAg.
- Patients must be receiving antiviral treatment with nucleoside analogs and have negative HBV DNA (defined as HBV DNA <20 IU/mL).
- Conditions
- Hepatitis B Virus (HBV)
- Being tested
- T101 Group, Placebo Group
- Keywords
- Hepatitis B virus (HBV) infection
- Medical subject headings
- Hepatitis B, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T101 GroupBiological
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.
Placebo GroupBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Placebo Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Evaluate the efficacy of T101
Measured: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
HBeAg quantitative levels
Evaluate the efficacy of T101
Measured: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Ad5 neutralizing antibodies
Use Analysis of luciferase Ad5 neutralizing antibody method to evaluate the changes of NAd5 titers after T101 administration
Measured: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Cellular and humoral immune responses
Detect the T-cell responses by interferon-γ（INF-γ） ELISPOT
Measured: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2019
- Study start8 Jan 2018
- Primary completion14 Oct 2019
- Study completion14 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B Virus (HBV)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tasly Tianjin Biopharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04168333
- Sponsor's protocol ID
- TC-2017-001
- Status last verified
- Dec 2019
- First submitted
- 24 Oct 2019
- Last updated
- 4 Dec 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single Center, Randomized, Double-blind, Placebo Controlled, Single Dose (SD) and Multiple Dose (MD), Dose-escalation Clinical Trial to Evaluate the Tolerability and Preliminary Antiviral Activity of Therapeutic Hepatitis B Adenovirus Injection (T101) in Chronic Hepatitis B Patients
- ClinicalTrials.gov ID
- NCT04168333
- Acronym / sponsor ID
- TC-2017-001
- Conditions
- Hepatitis B Virus (HBV)
- Keywords
- Hepatitis B virus (HBV) infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Tasly Tianjin Biopharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 14 Oct 2019 (actual)
- Study completion
- 14 Oct 2019 (actual)
- First posted
- 19 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a randomized, double-blind, placebo-controlled, single dose (SD) and multiple dose (MD) administration study.
Primary Objective: Safety and tolerability;
Secondary Objective:
- Antiviral activity of T101 (HBsAg levels).
- Cellular (HBV-specific) and humoral (AD5 neutralizing antibodies, NAd5) immune responses to T101.
Key Inclusion Criteria:
- Chronic hepatitis B patients with positive HBsAg.
- Patients must be receiving antiviral treatment with nucleoside analogs and have negative HBV DNA (defined as HBV DNA <20 IU/mL).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| T101 Group | Active comparator | Biological: T101 GroupThe 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. |
| Placebo Group | Placebo comparator | Biological: Placebo GroupThe 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 1) Signed, written Independent Ethics Committee (IEC)-approved informed consent.
- 2) Patients can cooperate to finish the trial in accordance with the requirements of protocol.
- 3）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.
- 4) 18 through 65 years of age, inclusive.
- 5）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.
Key exclusion criteria (20 listed)
- 1) Addicted to smoking (>5 cigarettes per day) for 3 months prior to the initiation of trial.
- 2) Subjects susceptible to allergies, including a history of allergy to investigational medical product (IMP) or its buffer.
- 3) 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).
- 4) Patients who have donated or lost an amount of blood> 450ml within 3 months prior to the screening of the trial.
- 5) 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| T101 GroupSingle 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. | Biological | T101 Group |
| Placebo GroupSingle 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. | Biological | Placebo Group |
Primary outcome
Adverse events
Time frame: through study completion, an average of 1 year
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
Vital signs index
Time frame: 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.
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.
Routine blood test
Time frame: 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.
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.
Blood biochemical test
Time frame: 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.
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.
Coagulation function test
Time frame: 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.
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.
Routine urinalysis
Time frame: 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.
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.
4 secondary outcomes
HBsAg quantitative levels
Time frame: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
HBeAg quantitative levels
Time frame: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Ad5 neutralizing antibodies
Time frame: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Cellular and humoral immune responses
Time frame: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing T101 Group in people with Hepatitis B Virus (HBV), run by Tasly Tianjin Biopharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: through study completion, an average of 1 year). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2019.