Chronic Hepatitis BPhase 1NCT03585322
APG-1387 Study of Safety, Tolerability ,PK/PD in Patients With Chronic Hepatitis B
A Phase 1 study testing APG-1387 for Injection in people with Chronic Hepatitis B, run by Ascentage Pharma Group Inc. at 2 sites in China.
Trial summary
This study is a Multiple Ascending Dose study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of APG-1387 in Chronic Hepatitis B Patients. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- APG-1387 for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 2 sitesChina
- Study dates
- 4 Jul 2018to 15 Oct 2021
- 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
- Age ≥18 and ≤ 65 years old.
- Confirmed diagnosis of chronic hepatitis B, HBsAg positive≥6 months.
- HBV DNA≥2×103 IU/mL for HBeAg negative patients, HBV DNA≥1×104IU/mL for HBeAg positive patients in screening phase.
- ALT≥ ULN and <10 ×ULN in screening phase (exclude non-HBV related ALT elevation such as drug or alcohol et al).
- BMI 18~26.
- Patients should not use antivirus treatment such as NAs and IFN within 6 months before screening.
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- Adequate hematologic function.
- QTc interval ≤ 450 ms in males, and ≤ 470 ms in females.
- Adequate renal and liver function.
- Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour prior to the first dose of investigational product. Willing to use contraception by a method that is deemed effective by the investigator by Subject and their partners throughout the treatment period and for at least three months following the last dose of study drug.
- Ability to understand and willing to sign a written informed consent form, the consent form must be signed by the patient prior to any study-specific procedures.
Who cannot join
- Clinical confirmed HCC or suspected HCC or AFP>50μg/L.
- A history of decompensated liver function (such as Child-Pugh B or C or history of ascites, digestive tract bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis et al.).
- Advanced fibrosis/cirrhosis, defined as a fiber screening scan≥12.4kPa during screening phase or liver biopsy at any time found Metavir score F3, F4 fibrosis.
- Patients with other liver diseases except hepatitis B, including chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, hereditary liver disease and other causes of active hepatitis.
- Patients with malignant tumours (excluding basal cell and in situ cervical cancer that have been cured without recurrence) or lymphatic proliferative diseases.
- Have a clear history of neurological or psychiatric disorders, such as epilepsy, dementia, poor compliance.
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- Chronic kidney disease, renal insufficiency.
- Poor control of other important primary diseases of the viscera, such as clear history of nervous system, cardiovascular system, urinary system, digestive system, respiratory system, Metabolism and skeletal muscle system (such as poor control diabetes, hypertension and etc.), which the investigator considers not suitable for the study.
- Females who are pregnant or nursing.
- History of alcoholism (average daily ethanol intake of 30 grams (male) or ≥ 20 grams (female) for 1 years), drug abuse history or drug abuse screening results positive.
- Severe infection, trauma or a major surgical operation within 4 weeks prior to screening.
- Use of immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) within 3 months prior to screening, or will use immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) during the study.
- Treatment with an investigational agent or device within three months prior to screening.
- Anti-HDV total antibody/IgM antibody positive, HCV antibody positive and HCV-RNA positive, anti-HIV antibody positive, or treponema pallidum antibody positive.
- Known or suspected Wilson's Disease, or other disease that may affect copper accumulates or regulates.
- Prior treatment with IAP inhibitors.
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510515
Guangzhou Eighth People's Hospital
Guangzhou, Guangdong
About this study
Official title: A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 in Patients With Chronic Hepatitis B.
This study is a Multiple Ascending Dose study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of APG-1387 in Chronic Hepatitis B Patients.
Read the detailed description
APG-1387 is a potent, bivalent small-molecule IAP antagonist. This study is multi-center, single-agent, open-label, Phase I dose-escalation study of APG-1387.
This study has a 4-dose-schedule which is escalated one by one after confirming safety in the previous lower dose schedule. A total of 60 subjects with Chronic Hepatitis B will be participated in the study. APG-1387 will be administrated via intravenous infusion, once a week for consecutive 4 weeks as one cycle.The start dose is 7mg. 3 patients' cohorts will be evaluated, the dose of APG-1387 will be increased in subsequent cohorts, to 12mg, 20 mg, 30 mg, 45 mg accordingly. 3 patients in 7mg,12mg cohorts and 6 patients in 20mg, 30mg and 45mg cohorts will be recruited. If there is any one of the following event is observed within 28 days of the first dose of APG-1387, the recruitment will be hold and a discussion on MTD dose level will happened.1 ≥1/2 patients experience ≥Grade 2 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387 and with clinical manifestation. 2 ≥1/3 patients experience ≥Grade 3 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387.3 any SAE related or possibly related with APG-1387. Expansion study will be designed to explore primary efficacy and safety after the dose escalation study. The expansion number and dosage will be decided according to the results of each cohort.(no more than 36 patients).
- Conditions
- Chronic Hepatitis B
- Being tested
- APG-1387 for Injection
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-1387 for InjectionDrug
Multiple dose cohorts, 30 minute IV infusion, once weekly for 4 weeks .
| Study group | Role | What they receive |
|---|---|---|
| APG-1387 for Injection | Experimental | APG-1387 will be explored sequentially using a escalation scheme at the dose escalation phase. Receives: Drug: APG-1387 for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0.3
Measured: 28 days
Secondary outcomes (8)
Pharmacokinetic evaluation
Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-1387.
Measured: 28 days
Pharmacokinetic evaluation
Area under the plasma concentration versus time curve (AUC) will be assessed in the patients treated with APG-1387 .
Measured: 28 days
Change in serum HBV DNA from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBsAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBeAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBsAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBeAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBcAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
treatment effects of APG-1387 on Chronic Hepatitis B
Measured: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2018
- Study start4 Jul 2018
- Primary completion15 Oct 2021
- Study completion15 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- dose escalation study
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- HealthQuest Pharma Inc.
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, M.D., Ph.D., Study director, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03585322
- Sponsor's protocol ID
- APG-1387-CN-HBV-001
- Status last verified
- Nov 2021
- First submitted
- 26 Jun 2018
- Last updated
- 8 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of APG-1387 in Patients With Chronic Hepatitis B.
- ClinicalTrials.gov ID
- NCT03585322
- Acronym / sponsor ID
- APG-1387-CN-HBV-001
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Collaborators
- HealthQuest Pharma Inc.
- Study start
- 4 Jul 2018 (actual)
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 15 Oct 2021 (actual)
- First posted
- 13 Jul 2018 (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.
This study is a Multiple Ascending Dose study to Explore the Tolerability, Safety and Pharmacokinetics/Pharmacodynamics of APG-1387 in Chronic Hepatitis B Patients.
Detailed description
APG-1387 is a potent, bivalent small-molecule IAP antagonist. This study is multi-center, single-agent, open-label, Phase I dose-escalation study of APG-1387.
This study has a 4-dose-schedule which is escalated one by one after confirming safety in the previous lower dose schedule. A total of 60 subjects with Chronic Hepatitis B will be participated in the study. APG-1387 will be administrated via intravenous infusion, once a week for consecutive 4 weeks as one cycle.The start dose is 7mg. 3 patients' cohorts will be evaluated, the dose of APG-1387 will be increased in subsequent cohorts, to 12mg, 20 mg, 30 mg, 45 mg accordingly. 3 patients in 7mg,12mg cohorts and 6 patients in 20mg, 30mg and 45mg cohorts will be recruited. If there is any one of the following event is observed within 28 days of the first dose of APG-1387, the recruitment will be hold and a discussion on MTD dose level will happened.1 ≥1/2 patients experience ≥Grade 2 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387 and with clinical manifestation. 2 ≥1/3 patients experience ≥Grade 3 toxicities[CTCAE 4.0.3] related or possibly related with APG-1387.3 any SAE related or possibly related with APG-1387. Expansion study will be designed to explore primary efficacy and safety after the dose escalation study. The expansion number and dosage will be decided according to the results of each cohort.(no more than 36 patients).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- dose escalation study
| Arm | Type | Receives |
|---|---|---|
| APG-1387 for Injection | Experimental | Drug: APG-1387 for InjectionAPG-1387 will be explored sequentially using a escalation scheme at the dose escalation phase. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥18 and ≤ 65 years old.
- Confirmed diagnosis of chronic hepatitis B, HBsAg positive≥6 months.
- HBV DNA≥2×103 IU/mL for HBeAg negative patients, HBV DNA≥1×104IU/mL for HBeAg positive patients in screening phase.
- ALT≥ ULN and <10 ×ULN in screening phase (exclude non-HBV related ALT elevation such as drug or alcohol et al).
- BMI 18~26.
Key exclusion criteria (17 listed)
- Clinical confirmed HCC or suspected HCC or AFP>50μg/L.
- A history of decompensated liver function (such as Child-Pugh B or C or history of ascites, digestive tract bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis et al.).
- Advanced fibrosis/cirrhosis, defined as a fiber screening scan≥12.4kPa during screening phase or liver biopsy at any time found Metavir score F3, F4 fibrosis.
- Patients with other liver diseases except hepatitis B, including chronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, hereditary liver disease and other causes of active hepatitis.
- Patients with malignant tumours (excluding basal cell and in situ cervical cancer that have been cured without recurrence) or lymphatic proliferative diseases.
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 |
|---|---|---|
| APG-1387 for InjectionMultiple dose cohorts, 30 minute IV infusion, once weekly for 4 weeks . | Drug | APG-1387 for Injection |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 28 days
Patients with APG-1387 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0.3
8 secondary outcomes
Pharmacokinetic evaluation
Time frame: 28 days
Pharmacokinetic evaluation
Time frame: 28 days
Change in serum HBV DNA from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBsAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBeAg from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBsAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBeAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
Change in serum HBcAb from baseline at Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84 and Day 112.
Time frame: Day 1, Day 8, Day15, Day 22, Day28，Day56，Day84，and Day 112
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 8 Nov 2021.
- Individual participant dataSharing planned: No
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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.
Yifan Zhai, M.D., Ph.D. study director
Ascentage Pharma Group Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APG-1387 for Injection in people with Chronic Hepatitis B, run by Ascentage Pharma Group Inc. at 2 sites 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 11 inclusion and 17 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 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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?
Maximum Tolerated Dose (MTD) (time frame: 28 days). 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 8 Nov 2021.