Treatment of Patients with Chronic Hepatitis B with Hepatitis B Immunoglobulins (HBIG)

Hannover Medical School (MHH)

Status and phase: Enrolling; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: Human hepatitis B Immunoglobulin (Hepatect®CP/Zutectra®)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05345990

HBIGforcure

2021-005362-18 (EudraCT Number)

Details and patient eligibility

About

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®.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

1. Willing and able to provide written informed consent

2. Male or female, age ≥ 18 years

3. Confirmation of chronic HBV infection documented by:

   positive HBsAg at least 12 months before screening

4. 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.

5. 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.

6. 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.

7. Transient Elastography (FibroScan) < 7.5 kPa at screening.

8. ALT levels < 1.5 times of upper the limit of normal at screening for both cohorts

9. Body mass idex (BMI) > 18kg/m²

10. 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

11. 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:

1. 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.
2. 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.
3. Clinical hepatic decompensation (i.e. clinical ascites, encephalopathy or variceal hemorrhage).
4. 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.
5. Significant drug allergy (such as anaphylaxis or hepatotoxicity).
6. Pregnant or nursing female or male with pregnant female partner
7. 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.
8. 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
9. A recent SARS-COV2 infection in the last 4 weeks prior to screening

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Hepatitis B immunoglobulins

Experimental group

Description:

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

Treatment:

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