Treatment of Patients With Chronic Hepatitis B With Hepatitis B Immunoglobulins

Study Overview
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Brief Summary
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This is an open-label, single arm (two cohorts), single-center, phase II pilot-study to provide preliminary evidence whether hepatitis B immunoglobulins (HBIG) are efficacious and can be safely used in patients with chronic Hepatitis B Virus (HBV) infection. A total of 20 patients (male or female adults aged ≥ 18 years) will be enrolled in the study and receive hepatitis B immunoglobulins Hepatect®CP and Zutectra®.

Official Title
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Hepatitis B Immunoglobulins to Induce HBsAg Clearance in Patients With Chronic Hepatitis B (HBIG for Cure)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Human hepatitis B Immunoglobulin (Hepatect®CP/Zutectra®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all of the following inclusion criteria to be eligible for participation in this study: Willing and able to provide written informed consent Male or female, age ≥ 18 years Confirmation of chronic HBV infection documented by: positive HBsAg at least 12 months before screening Cohort A: NA treatment for at least 12 months before screening. HBV-DNA should be below the lower limit of detection at screening. HBsAg positive and <100 IU/ml. HBeAg negative. Cohort B: Untreated with NAs for at least 12 months before screening. HBV-DNA < 2000 IU/ml. HBsAg positive and < 100 IU/ml. HBeAg-negative. Subject has not been treated with any investigational drug or device within 42 days before the screening visit or within 5 half-lives for investigational drugs, whichever is longer. Transient Elastography (FibroScan) < 7.5 kPa at screening. ALT levels < 1.5 times of upper the limit of normal at screening for both cohorts Body mass idex (BMI) > 18kg/m² A negative serum pregnancy test is required for female subjects (unless surgically sterile or women > 54 years of age with cessation for > 24 months of previously occurring menses). Complete abstinence from intercourse. Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) is not permitted. Or Consistent and correct use of 1 of the following methods of birth control listed below, in addition to a male partner who correctly uses a condom, from the date of Screening until the end of FU: intrauterine device (IUD) with a failure rate of < 1% per year bilateral tubal sterilization vasectomy in male partner hormone-containing contraceptive: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral intravaginal transdermal progestogen-only hormonal contraception associated with inhibition of ovulation: oral injectable implantable Subject must be able to comply with the dosing instructions for study drug administration and be able to complete the study schedule of assessments Exclusion Criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study: Clinically significant illness (other than hepatitis B) or any other major medical disorder that, in the opinion of the investigator, may interfere with subject treatment, assessment or compliance with the protocol. Subjects currently under evaluation for a potentially clinically significant illness (other than hepatitis B) are also excluded. Co-infection with hepatitis C virus (defined as HCV RNA positive. HCV RNA negative/anti-HCV-positive patients can be included) or co-infection with HIV. Clinical hepatic decompensation (i.e. clinical ascites, encephalopathy or variceal hemorrhage). Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 2 years. Subjects with psychiatric illness that is well-controlled on a stable treatment regimen for at least 12 months prior to screening or has not required medication in the last 12 months may be included. Significant drug allergy (such as anaphylaxis or hepatotoxicity). Pregnant or nursing female or male with pregnant female partner Clinically relevant drug or alcohol abuse within 12 months of screening including any uncontrolled drug use within 6 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication. The investigator must approve medication, the diagnosis and prescription. Uncontrolled users of intravenous drugs will not be permitted to enroll in the study. live-attenuated virus vaccinations such as: measles, mumps, rubella and varicella 4 weeks before and up to three months after administration of hepatitis B immunoglobulins. If not required by an emergency situation, passive or active immunizations or administration of plasma preparations or of other immunoglobulins is not allowed during the study A recent SARS-COV2 infection in the last 4 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients treated in two cohorts for 12 weeks with hepatitis B immunoglobulins
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepatitis B immunoglobulins<br>20 patients treated in two cohorts for 12 weeks with hepatitis B Immunoglobulins (HBIG, Hepatect®CP/ Zutectra®). Cohort A: 10 HBsAg positive, HBeAg-negative patients being treated with anti-HBV nucleotide or nucleoside analogous (NAs) for at least 12 months before screening. HBV-DNA should be below the lower limit of detection at screening. HBsAg should be positive and below 100 IU/ml. Cohort B: 10 HBsAg positive, HBeAg-negative patients untreated with NAs for at least 12 months before screening. Patients with HBV-DNA levels below 2000 IU/ml and ALT < 1.5 times upper the limit of normal. HBsAg should be positive and below 100 IU/ml. Trial duration: A recruiting period of approximately 6 months is planned. The total time per patient to complete all study visits is approximately 40 weeks including: an 28 day screening period an 12 week treatment period an 24 week follow-up period | Drug: Human hepatitis B Immunoglobulin (Hepatect®CP/Zutectra®)<br>* Hepatect® is a solution to be administered Intravenously. Zutectra® is a solution to be administered subcutaneously. Treatment for 12 weeks with hepatitis B immunoglobulins with following administration scheme: D0: 10.000 IU Hepatect® i.v. D1-6: 500 IU Zutectra® s.c. D7: 10.000 IU Hepatect® i.v. D9- D84: 500 IU Zutectra® s.c. every 2nd day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of 12-weeks treatment with hepatitis B immunoglobulins in two different cohorts of patients with chronic hepatitis B defined by the proportion of subjects being HBsAg negative at treatment week 12 | Primary efficiency endpoint: HBsAg negativity at week 12 of antiviral therapy | week 12 of antiviral therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To analyze the change/decline of HBsAg during treatment | Secondary endpoint: HBsAg change/decline at weeks 1, 2, 4, 8 and 12 of treatment | week 1, 2, 4, 8 and 12 of treatment | 
| To evaluate the post-treatment HBsAg kinetics/response | Secondary endpoint: Post-treatment HBsAg negativity up to FU week 24 | Follow-up (FU) week 2, FU week 4, FU week 12 and FU week 24 | 
| To determine HBV-DNA levels during and after treatment with hepatitis B immunoglobulins | Secondary endpoint: HBV DNA levels during and after hepatitis B immunoglobulin treatment will be reported for each cohort. | screening, day 0, day 1, day 3, day 7, day 28, day 42, day 84, FU week 12 and FU week 24 | 
| To evaluate the biochemical disease activity (normalization of serum ALT levels) | Secondary endpoint: biochemical response (proportion of subjects who reached ALT normalization (ALT ≤ ULN) at week 12 of treatment) | week 12 of treatment | 
| To determine the quality of life by SF-36 questionnaire | Secondary endpoint: quality of life during treatment and follow-up (SF-36) | day 0, day 84, FU week 12, FU week 24 | 
| Assessment of safety by collection of adverse events (AEs) as frequencies (absolute/relative). | Adverse events (AEs) will be collected throughout the study (upon first administration of the IMPs up to 24 weeks after discontinuation of therapy, FU24) and will be reported with absolute and relative frequencies along with the corresponding 95% confidence intervals | day 0, day 1, day 3, day 7, day 14, day 21, day 28, day 42, day 56, day 84, FU week 2, FU week 4, FU week 12, FU week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human hepatitis B Immunoglobulin