Chronic Hepatitis BPhase 4COSTNCT03357822
A Real-World Study of Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B
A Phase 4 study testing Pegylated interferon, Entecavir and Tenofovir disoproxil fumarate in people with Chronic Hepatitis B, run by Tongji Hospital at 12 sites in China.
Trial summary
The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment. 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?
- Pegylated interferon, Entecavir and Tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 12 sitesChina
- Study dates
- 25 Jan 2018to 25 Jul 2022
- 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 ≤ 500 copies/ml;
- HBsAg<3000 IU/ml;
- HBsAg positive;
Show all 9Show fewer
- 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
- HBV DNA > 500 copies/ml;
- 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:
Show all 25Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
China12 sites, 12 recruiting
- Recruiting
302 Military Hospital of China
Beijing, Beijing Municipality
Junliang Fu
- Not yet recruiting
BeiJing YouAn Hospital, Capital Medical University
Beijing, Beijing Municipality
Xinyue Chen, Doctor
- Not yet recruiting
Departmen of infectious disease, Xiangya Hospital, Central-south Universit
Changsha, Hunan
Deming Tan, Doctor
- Not yet recruiting
The Second Xiangya Hospital of Central South University
Changsha, Hunan
Guozhong Gong
- Not yet recruiting
The First Hospital Affiliated to AMU
Chongqing, Chongqing Municipality
Xuqing Zhang
- Not yet recruiting
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Jiaji Jiang, Doctor
- Not yet recruiting
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu
Chuanlong Zhu
- Not yet recruiting
The Second Hospital of Nanjing
Nanjing, Jiangsu
Wei Zhao
- Not yet recruiting
The First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi
- Not yet recruiting
Traditional Chinese Medicine,Xiamen Hospital
Shantou, Xiamen
Qianguo Mao
- Not yet recruiting
The first affiliated hospital of Wenzhou medical universtiy
Wenzhou, Zhejiang
Yongping Chen, Doctor
- Not yet recruiting
The First Affiliated Hospital of College of Medicine, Zhejiang University
Zhejiang, Hangzhou, Doctor
Qi Xia
About this study
Official title: A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B
The aim of the prospective real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment.
Read the detailed description
Patents who were treated with NA at least one year and achieved hepatitis B virus (HBV) DNA suppression and HBsAg level<3000 international unit (IU) /mL are enrolled in this study, they are assigned into two groups, in group I, patients will receive pegylated interferon plus entecavir/tenofovir for 48/72/96 weeks, in group II, patients will receive entecavir/tenofovir for 96 weeks. HBsAg loss rates at the end of treatment and sustained response at the end of follow up will be evaluated.
- Conditions
- Chronic Hepatitis B
- Being tested
- Pegylated interferon, Entecavir, Tenofovir disoproxil fumarate
- Keywords
- Chronic hepatitis B, Nucleoside analog, Pegylated Interferon, Sequential combination therapy, HBsAg loss
- 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.
Pegylated interferonDrug
Also called Pegylated interferon (PegIFN)
180ug Pegylated interferon is injected subcutaneously once a week
EntecavirDrug
Also called Entecavir (ETV)
0.5mg entecavir is orally taken every day
Tenofovir disoproxil fumarateDrug
Also called Tenofovir disoproxil fumarate (TDF)
300mg tenofovir is orally taken every day
| Study group | Role | What they receive |
|---|---|---|
| Sequential combination therapy group | Experimental | Patients are treated with pegylated Interferon (180ug, subcutaneously, once a week) plus entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 48/72/96 weeks Receives: Drug: Pegylated interferon; Drug: Entecavir; Drug: Tenofovir disoproxil fumarate |
| Nucleoside therapy group | Active comparator | Patients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks Receives: Drug: Entecavir; Drug: Tenofovir disoproxil fumarate |
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 week 48
Measured: at week 48
Secondary outcomes (25)
HBsAg loss rate
Percentages of patients who achieve HBsAg loss at week 72
Measured: at week 72
HBsAg loss rate
Percentages of patients who achieve HBsAg loss at week 96
Measured: at week 96
HBsAg level
Dynamic change in HBsAg level from baseline to week 48
Measured: at week 48
HBsAg level
Dynamic change in HBsAg level from baseline to week 72
Measured: at week 72
HBsAg level
Dynamic change in HBsAg level from baseline to week 96
Measured: at week 96
sustained HBsAg loss rate
Percentages of patients who achieve HBsAg loss at week 120
Measured: at week 120
decline in HBsAg level
Decline in HBsAg level from baseline to week 48
Measured: at week 48
decline in HBsAg level
Decline in HBsAg level from baseline to week 72
Measured: at week 72
decline in HBsAg level
Decline in HBsAg level from baseline to week 96
Measured: at week 96
HBsAb appearance rate
Percentages of HBsAb appearance at week 48
Measured: at week 48
HBsAb appearance rate
Percentages of HBsAb appearance at week 72
Measured: at week 72
HBsAb appearance rate
Percentages of HBsAb appearance at week 96
Measured: at week 96
HBsAb seroconversion rate
Percentages of HBsAb seroconversion at week 48
Measured: at week 48
HBsAb seroconversion rate
Percentages of HBsAb seroconversion at week 72
Measured: at week 72
HBsAb seroconversion rate
Percentages of HBsAb seroconversion at week 96
Measured: at week 96
HBeAg loss rate
Percentages of HBeAg loss in the HBeAg-positive patients at week 48
Measured: at week 48
HBeAg loss rate
Percentages of HBeAg loss in the HBeAg-positive patients at week 72
Measured: at week 72
HBeAg loss rate
Percentages of HBeAg loss in the HBeAg-positive patients at week 96
Measured: at week 96
HBeAg seroconversion rate
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 48
Measured: at week 48
HBeAg seroconversion rate
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 72
Measured: at week 72
HBeAg seroconversion rate
Percentages of HBeAg seroconversion in the HBeAb-negative patients at week 96
Measured: at week 96
Rate of HBV DNA level <1000 copies/mL
Percentages of HBV DNA level <1000 copies/mL at week 96
Measured: at week 96
Rate of alanine aminotransferase (ALT) normalization
Percentages of ALT normalization at week 96
Measured: at week 96
The rate of progression to cirrhosis
The rate of progression to cirrhosis at week 120
Measured: at week 120
The incidence rate of hepatocarcinoma
The incidence rate of hepatocarcinoma at week 120
Measured: at week 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2017
- Study start25 Jan 2018
- Primary completion25 Jan 2022 (estimated)
- Study completion25 Jul 2022 (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.
- More trials run by Tongji HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qin Ning, Tongji Hospital
- Investigators
- Qin Ning, Principal investigator, Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03357822
- Sponsor's protocol ID
- COST study
- Acronym
- COST
- Status last verified
- Apr 2018
- First submitted
- 20 Nov 2017
- Last updated
- 25 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Real-World Study of Sequential Combination Therapy With Pegylated Interferon In Nucleoside-treated Patients With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT03357822
- Acronym / sponsor ID
- COST / COST study
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic hepatitis B, Nucleoside analog, Pegylated Interferon, Sequential combination therapy, HBsAg loss
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 25 Jan 2018 (actual)
- Primary completion
- 25 Jan 2022 (estimated)
- Study completion
- 25 Jul 2022 (estimated)
- First posted
- 30 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 real-world study is to evaluate whether sequential combination therapy with pegylated interferon plus entecavir/tenofovir could induce higher rates of HBsAg loss in nucleoside-treated patients with chronic hepatitis B compared to continuous nucleoside treatment.
Detailed description
Patents who were treated with NA at least one year and achieved hepatitis B virus (HBV) DNA suppression and HBsAg level<3000 international unit (IU) /mL are enrolled in this study, they are assigned into two groups, in group I, patients will receive pegylated interferon plus entecavir/tenofovir for 48/72/96 weeks, in group II, patients will receive entecavir/tenofovir for 96 weeks. HBsAg loss rates at the end of treatment and sustained response at the end of follow up will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequential combination therapy group | Experimental | Drug: Pegylated interferon, Drug: Entecavir, Drug: Tenofovir disoproxil fumaratePatients are treated with pegylated Interferon (180ug, subcutaneously, once a week) plus entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 48/72/96 weeks |
| Nucleoside therapy group | Active comparator | Drug: Entecavir, Drug: Tenofovir disoproxil fumaratePatients are treated with entecavir (0.5mg, orally, every day) or tenofovir disoproxil fumarate (300mg, orally, every day) for 96 weeks |
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 ≤ 500 copies/ml;
- HBsAg<3000 IU/ml;
Key exclusion criteria (25 listed)
- HBV DNA > 500 copies/ml;
- 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 |
|---|---|---|
| Pegylated interferonAlso: Pegylated interferon (PegIFN)180ug Pegylated interferon is injected subcutaneously once a week | Drug | Sequential combination therapy group |
| EntecavirAlso: Entecavir (ETV)0.5mg entecavir is orally taken every day | Drug | Nucleoside therapy group, Sequential combination therapy group |
| Tenofovir disoproxil fumarateAlso: Tenofovir disoproxil fumarate (TDF)300mg tenofovir is orally taken every day | Drug | Nucleoside therapy group, Sequential combination therapy group |
Primary outcome
HBsAg loss rate
Time frame: at week 48
Percentages of patients who achieve HBsAg loss at week 48
25 secondary outcomes
HBsAg loss rate
Time frame: at week 72
HBsAg loss rate
Time frame: at week 96
HBsAg level
Time frame: at week 48
HBsAg level
Time frame: at week 72
HBsAg level
Time frame: at week 96
sustained HBsAg loss rate
Time frame: at week 120
decline in HBsAg level
Time frame: at week 48
decline in HBsAg level
Time frame: at week 72
decline in HBsAg level
Time frame: at week 96
HBsAb appearance rate
Time frame: at week 48
HBsAb appearance rate
Time frame: at week 72
HBsAb appearance rate
Time frame: at week 96
HBsAb seroconversion rate
Time frame: at week 48
HBsAb seroconversion rate
Time frame: at week 72
HBsAb seroconversion rate
Time frame: at week 96
HBeAg loss rate
Time frame: at week 48
HBeAg loss rate
Time frame: at week 72
HBeAg loss rate
Time frame: at week 96
HBeAg seroconversion rate
Time frame: at week 48
HBeAg seroconversion rate
Time frame: at week 72
HBeAg seroconversion rate
Time frame: at week 96
Rate of HBV DNA level <1000 copies/mL
Time frame: at week 96
Rate of alanine aminotransferase (ALT) normalization
Time frame: at week 96
The rate of progression to cirrhosis
Time frame: at week 120
The incidence rate of hepatocarcinoma
Time frame: at week 120
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2018.
Related trials for Chronic Hepatitis B
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 2
Study of Bepirovirsen in Participants Living With Human Immunodeficiency Virus and Chronic Hepatitis B Virus Infection (B-Focus)
Hepatitis B
Active, not recruitingPhase 2
Long-term Follow-up Study to Evaluate Durability of Treatment Response in Previous Bepirovirsen Study Participants (B-Sure)
Hepatitis B
Enrolling by invitationPhase 1
A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
Chronic Hepatitis B
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
Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pegylated interferon, Entecavir and Tenofovir disoproxil fumarate in people with Chronic Hepatitis B, run by Tongji Hospital at 12 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 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 25 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 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 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?
Contact Qin Ning (86 27 83662391, qning@vip.sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBsAg loss rate (time frame: at week 48). 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 25 Apr 2018.