Chronic Hepatitis bPhase 4NPGVNCT03332329
Sequential/Combination Therapy in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients
A Phase 4 study testing Entecavir, Granulocyte Macrophage Colony Stimulating Factor and Y peginterferon alfa-2b in people with Chronic Hepatitis b, run by Qin Ning.
Trial summary
The aim of the prospective study is to determine whether combination/ sequential therapy with Entecavir, Peginterferon alfa-2b and immunomodulators Granulocyte Macrophage Colony Stimulating Factor (GMCSF)+vaccine could induce HBsAg loss in chronic hepatitis B patients with maintained Hepatitis B Virus (HBV) DNA… 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?
- Entecavir, Granulocyte Macrophage Colony Stimulating Factor and Y peginterferon alfa-2b
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2015to 31 Dec 2019
- Phase
- Phase 4
- 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
- Male and female patients from 18 to 65 years of age;
- HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
- Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;
- Serum HBV DNA < 1000 copies/ml;
- 2000 IU/ml ≤HBsAg≤6000 IU/ml;
- HBsAg positive;
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- Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;
- Absence of cirrhosis confirmed by ultrasonic test;
- Agree to participate in the study and sign the patient informed consent.
Who cannot join
- Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugs with interferon longer than 6 months;
- Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
- Women with ongoing pregnancy or breast-feeding;
- Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
- ALT >10 ULN;
- Evidence of decompensated liver disease (Child-Pugh score > 5). Child-Pugh > 5 means, if one of the following 5 conditions are met, the patient has to be excluded:
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- one of the following 5 conditions are met, the patient has to be excluded:
- Serum albumin < 3.5 g/L;
- Prothrombin time > 3 seconds prolonged;
- Serum bilirubin > 34 µ mol/L;
- History of encephalopathy;
- History of variceal bleeding;
- Ascites;
- History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
- Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;
- Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
- Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
- Serum creatinine level > 1.5 ULN in screening period.
- Phosphorus < 0.65 mmol/L;
- antinuclear antibody (ANA) > 1:100;
- History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
- History of a severe seizure disorder or current anticonvulsant use;
- History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
- History of chronic pulmonary disease associated with functional limitation;
- Diseases that interferon and Nucleotides or nucleosides are not suitable.
About this study
Official title: Efficacy and Safety of Combination Therapy With Entecavir, Peginterferon Alfa-2b and Immunomodulators in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients
The aim of the prospective study is to determine whether combination/ sequential therapy with Entecavir, Peginterferon alfa-2b and immunomodulators Granulocyte Macrophage Colony Stimulating Factor (GMCSF)+vaccine could induce HBsAg loss in chronic hepatitis B patients with maintained Hepatitis B Virus (HBV) DNA suppression on long-term nucleoside or nucleotide analogue (NA).
Read the detailed description
Patents who were treated with NA at least one year and achieved HBV DNA suppression are enrolled in this study, they will receive Entecavir (ETV) for 60 weeks, HBV vaccine (60ug/month, every four weeks) for 24 weeks, GMCSF (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84, and Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108.
- Conditions
- Chronic Hepatitis b
- Being tested
- Entecavir, Granulocyte Macrophage Colony Stimulating Factor, Y peginterferon alfa-2b, HBV vaccine
- Keywords
- HBsAg, PegIFN, ETV, Chronic Hepatitis B (CHB), HBV, GMCSF
- 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.
EntecavirDrug
Also called ETV
Entecavir is used for 96 weeks
Granulocyte Macrophage Colony Stimulating FactorDrug
Also called GMCSF
Granulocyte-macrophage colony stimulating factor is used intermittently from baseline to week 16 and from 60 to week 84
Y peginterferon alfa-2bDrug
Also called peginterferon a-2b
Y peginterferon alfa-2b is used for 96 weeks
HBV vaccineDrug
Also called vaccine
60ug HBV vaccine is used every four week for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sequential combination arm | Experimental | Drug: Entecavir for 60 weeks Drug: HBV vaccine (60ug/month, every four weeks) for 24 weeks Drug: Granulocyte Macrophage Colony Stimulating Factor (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84 Drug: Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108 Receives: Drug: Entecavir; Drug: Granulocyte Macrophage Colony Stimulating Factor; Drug: Y peginterferon alfa-2b; Drug: HBV vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBsAg loss rate
Percentages of patients who achieve HBsAg loss at the end of treatment
Measured: at week 108
Secondary outcomes (13)
HBsAg level
Dynamic change in HBsAg level from baseline to the end of treatment
Measured: at week 60
HBsAg level
Dynamic change in HBsAg level from baseline to the end of treatment
Measured: at week 108
decline in HBsAg level
Decline in HBsAg level from baseline to the end of treatment
Measured: at week 60
decline in HBsAg level
Decline in HBsAg level from baseline to the end of treatment
Measured: at week 108
HBsAb appearance rate
Percentages of HBsAb appearance at the end of treatment
Measured: at week 108
HBsAb seroconversion rate
Percentages of HBsAb seroconversion at the end of treatment
Measured: at week 108
HBeAg loss rate
Percentages of HBeAg loss in the HBeAg-positive patients at the end of treatment
Measured: at week 108
HBeAg seroconversion rate
Percentages of HBeAg seroconversion in the HBeAb-negative patients at the end of treatment
Measured: at week 108
Rate of HBV DNA level <1000 copies/mL
Percentages of HBV DNA level <1000 copies/mL at the end of treatment
Measured: at week 108
Rate of alanine aminotransferase (ALT) normalisation
Percentages of ALT normalisation at the end of treatment
Measured: at week 108
Sustained HBsAg loss rate
Percentages of sustained HBsAg loss at the end of follow-up
Measured: at week 156
The rate of progression to cirrhosis
The rate of progression to cirrhosis at the end of follow-up
Measured: at week 156
The incidence rate of hepatocarcinoma
The incidence rate of hepatocarcinoma at the end of follow-up
Measured: at week 156
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start1 Dec 2015
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (estimated)
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.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Qin Ning
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Qin Ning, Tongji Hospital
- Investigators
- Qin Ning, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332329
- Sponsor's protocol ID
- NPGV study
- Acronym
- NPGV
- Status last verified
- Nov 2017
- First submitted
- 29 Oct 2017
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Combination Therapy With Entecavir, Peginterferon Alfa-2b and Immunomodulators in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients
- ClinicalTrials.gov ID
- NCT03332329
- Acronym / sponsor ID
- NPGV / NPGV study
- Conditions
- Chronic Hepatitis b
- Keywords
- HBsAg, PegIFN, ETV, Chronic Hepatitis B (CHB), HBV, GMCSF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Qin NingUniversity, hospital or other
- Study start
- 1 Dec 2015 (actual)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 6 Nov 2017 (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.
The aim of the prospective study is to determine whether combination/ sequential therapy with Entecavir, Peginterferon alfa-2b and immunomodulators Granulocyte Macrophage Colony Stimulating Factor (GMCSF)+vaccine could induce HBsAg loss in chronic hepatitis B patients with maintained Hepatitis B Virus (HBV) DNA suppression on long-term nucleoside or nucleotide analogue (NA).
Detailed description
Patents who were treated with NA at least one year and achieved HBV DNA suppression are enrolled in this study, they will receive Entecavir (ETV) for 60 weeks, HBV vaccine (60ug/month, every four weeks) for 24 weeks, GMCSF (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84, and Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sequential combination arm | Experimental | Drug: Entecavir, Drug: Granulocyte Macrophage Colony Stimulating Factor, Drug: Y peginterferon alfa-2b, Drug: HBV vaccineDrug: Entecavir for 60 weeks Drug: HBV vaccine (60ug/month, every four weeks) for 24 weeks Drug: Granulocyte Macrophage Colony Stimulating Factor (75 μg/day, first 5 days each month, subcutaneous) from baseline to week 16 and from week 60 to week 84 Drug: Y peginterferon alfa-2b (180 μg/week, subcutaneous) from week 16 to week 108 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male and female patients from 18 to 65 years of age;
- HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history;
- Before nucleotides or nucleosides treatment, ALT > 2 upper limit of normal value (ULN), HBV DNA >10000 copies/ml, HBsAg positive;
- Serum HBV DNA < 1000 copies/ml;
- 2000 IU/ml ≤HBsAg≤6000 IU/ml;
Key exclusion criteria (25 listed)
- Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugs with interferon longer than 6 months;
- Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
- Women with ongoing pregnancy or breast-feeding;
- Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
- ALT >10 ULN;
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 |
|---|---|---|
| EntecavirAlso: ETVEntecavir is used for 96 weeks | Drug | Sequential combination arm |
| Granulocyte Macrophage Colony Stimulating FactorAlso: GMCSFGranulocyte-macrophage colony stimulating factor is used intermittently from baseline to week 16 and from 60 to week 84 | Drug | Sequential combination arm |
| Y peginterferon alfa-2bAlso: peginterferon a-2bY peginterferon alfa-2b is used for 96 weeks | Drug | Sequential combination arm |
| HBV vaccineAlso: vaccine60ug HBV vaccine is used every four week for 24 weeks | Drug | Sequential combination arm |
Primary outcome
HBsAg loss rate
Time frame: at week 108
Percentages of patients who achieve HBsAg loss at the end of treatment
13 secondary outcomes
HBsAg level
Time frame: at week 60
HBsAg level
Time frame: at week 108
decline in HBsAg level
Time frame: at week 60
decline in HBsAg level
Time frame: at week 108
HBsAb appearance rate
Time frame: at week 108
HBsAb seroconversion rate
Time frame: at week 108
HBeAg loss rate
Time frame: at week 108
HBeAg seroconversion rate
Time frame: at week 108
Rate of HBV DNA level <1000 copies/mL
Time frame: at week 108
Rate of alanine aminotransferase (ALT) normalisation
Time frame: at week 108
Sustained HBsAg loss rate
Time frame: at week 156
The rate of progression to cirrhosis
Time frame: at week 156
The incidence rate of hepatocarcinoma
Time frame: at week 156
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Individual participant dataSharing planned: Undecided
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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.
Qin Ning principal investigator
Tongji Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entecavir, Granulocyte Macrophage Colony Stimulating Factor and Y peginterferon alfa-2b in people with Chronic Hepatitis b, run by Qin Ning.
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 9 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
HBsAg loss rate (time frame: at week 108). 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 6 Nov 2017.