Clinical trial NCT05345990: Treatment of Patients With Chronic Hepatitis B With Hepatitis B Immunoglobulins
Official title: Hepatitis B Immunoglobulins to Induce HBsAg Clearance in Patients With Chronic Hepatitis B (HBIG for Cure)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Human hepatitis B Immunoglobulin
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: Biotest
First posted: 2022-04-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients treated in two cohorts for 12 weeks with hepatitis B immunoglobulins
Primary purpose: TREATMENT

Brief summary: 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®.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: week 12 of antiviral therapy
Secondary outcomes:
measure: To analyze the change/decline of HBsAg during treatment
timeFrame: week 1, 2, 4, 8 and 12 of treatment
measure: To evaluate the post-treatment HBsAg kinetics/response
timeFrame: Follow-up (FU) week 2, FU week 4, FU week 12 and FU week 24
measure: To determine HBV-DNA levels during and after treatment with hepatitis B immunoglobulins
timeFrame: screening, day 0, day 1, day 3, day 7, day 28, day 42, day 84, FU week 12 and FU week 24
measure: To evaluate the biochemical disease activity (normalization of serum ALT levels)
timeFrame: week 12 of treatment
measure: To determine the quality of life by SF-36 questionnaire
timeFrame: day 0, day 84, FU week 12, FU week 24
measure: Assessment of safety by collection of adverse events (AEs) as frequencies (absolute/relative).
timeFrame: 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
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Hannover Medical School, Department for Gastroenterology, Hepatology and Endocrinology
state: Lower Saxony
Study officials:
affiliation: Hannover Medical School, Department of Gastroenterology, Hepatology and Endocrinology
name: Heiner Wedemeyer, Prof.
role: PRINCIPAL_INVESTIGATOR
References: