Clinical trial NCT06368882: Efficacy and Safety of Antiviral Therapy With Peg-interferon for Chronic Hepatitis B Complicated With Nonalcoholic Fatty Liver Disease（OCEAN PROJECT）
Official title: Efficacy and Safety of Antiviral Therapy With Peg-interferon for Chronic Hepatitis B Complicated With Nonalcoholic Fatty Liver Disease（OCEAN PROJECT）
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Nonalcoholic Fatty Liver Disease
Chronic Hepatitis b
Keywords: Nonalcoholic Fatty Liver Disease
Chronic Hepatitis B
Peg-Interferon α
nucleo(s)tide analogues
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, multicenter, open-label, non-randomized controlled real-world study to explore the efficacy and safety and to accumulate more evidence-based medical data of an antiviral treatment programme for chronic viral hepatitis B with nonalcoholic fatty liver disease.

A total of 1500 patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease are divided into test group (1000 patients receiving PEG-IFNα-based antiviral therapy (combined NAs or Peg-IFNα monotherapy) and control group（500 patients receiving NAs monotherapy） according to their treatment intention. Laboratory and medical data from specified follow-up points are collected, and adverse events and drug combinations are recorded detailly.

The primary efficacy indicator is HBsAg clearance at 48 weeks of treatment, and the secondary indicators included: (1) HBsAg clearance at 96 weeks of treatment, (2) Cumulative HBsAg clearance at week 24、120、144、168、192、216 and 240; (3) The improvement of liver function level(ALT, AST, TBIL, etc.), blood lipid (TC, TG, LDL-C, HDL-C, etc.), fasting blood glucose, insulin resistance index (HOMA-IR), controlled attenuation parameter, body mass index , liver stiffness measurement, liver histological fibrosis, FIB-4 index from baseline; (4)Incidence of liver cirrhosis and hepatocellular carcinoma during follow-up.

The security assessment includes adverse events, vital signs, and imaging.


Eligibility criteria: Inclusion Criteria:

1. Age of 18-60 years old, male or female (including 18 and 60 years old);
2. meet the diagnostic criteria for chronic hepatitis B in the Guidelines for the prevention and treatment of chronic hepatitis B (2022 edition), and meet the imaging diagnostic criteria for fatty liver in the guidelines for the prevention and treatment of non-alcoholic fatty liver disease (2018 Update edition).
3. serum HBsAg positive \>6 months;
4. NAs treatment: baseline HBsAg≤1500 IU/ml, HBeAg negative, HBV DNA negative (not detected);
5. IHC initial treatment: baseline HBsAg\<1000 IU/ml, HBeAg negative, HBV DNA negative (undetectable), ALT and AST persistently normal (ULN: \<50 IU/L in men, \<40 IU/L in women);
6. a negative serum pregnancy test within 24 hours before the first dose (for women of reproductive age);
7. willing to receive treatment and signed informed consent.

Exclusion Criteria:

1. co-infection with active hepatitis A, C, D, E and/or HIV; Or combined with drug-induced liver injury, inherited metabolic liver disease, autoimmune hepatitis, alcoholic liver disease;
2. Liver tumor was detected by liver imaging at the time of screening;
3. patients diagnosed with hepatitis B cirrhosis, that is, those with liver biopsy pathology consistent with liver cirrhosis, or with two or more of the following five criteria, excluding non-cirrhotic portal hypertension: ① imaging examination showed signs of liver cirrhosis and/or portal hypertension; ② Esophagogastric varices were found by endoscopy; ③ Liver stiffness was consistent with cirrhosis; ④ Blood biochemical examination showed decreased albumin level (\< 35 g/L) and/or prolonged prothrombin time (prolonged \> 3 seconds compared with the control); ⑤ Blood routine examination showed platelet count \< 100×109/L;
4. pregnant or lactating women or those who plan to become pregnant and do not want to use contraception during the study period;
5. neutrophil count \<1.5×109/L or platelet count \<90×109/L. Patients with creatinine higher than 1.5 times the upper limit of normal;
6. The patients and their close relatives (parents, siblings, etc.) had a history of severe mental illness, especially depression. Severe psychosis is defined as severe depression or psychosis, suicide attempt, hospitalization due to psychosis, or a period of incapacitation due to psychosis;
7. patients with a history of immune-mediated diseases (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis) or abnormally elevated levels of autoimmune antibodies;
8. patients with serious diseases of heart, lung, kidney, brain, blood and other important organs, and patients with other malignant tumors;
9. history of severe epilepsy or current use of antiepileptic drugs. Control of unstable diabetes, hypertension, thyroid disease, etc. A history of severe retinopathy or other evidence of retinopathy;
10. any history of organ transplantation and existing functional graft (except corneal or hair transplantation);
11. patients who are allergic to interferon and its drug components, and who are not suitable for interferon according to the investigator's judgment;
12. Patients deemed by the investigator to be ineligible for the study.

Primary outcomes:
measure: HBsAg clearance
timeFrame: 48 weeks
Secondary outcomes:
measure: HBsAg clearance at 96 weeks
timeFrame: 96 weeks
measure: Cumulative HBsAg clearance rate
timeFrame: week 24、72、120、144、168、192、216、240
measure: Liver Function Tests
timeFrame: week 24、48、72、96、120、144、168、192、216、240
measure: The incidence of liver cirrhosis and liver cancer
timeFrame: week 24、48、72、96、120、144、168、192、216、240
Other outcomes:
Locations:
city: Ningbo
country: China
facility: Ningbo No.2 Hospital
city: Rui'an
country: China
facility: Ruian People's Hospital
city: Wenzhou
country: China
facility: The Second Affiliated Hospital of Wenzhou Medical University
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
city: Yueqing
country: China
facility: Yueqing People's Hospital
Study officials:
References: