Effective treatment of Hepatitis B with specific immune antibodies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medizinische Hochschule Hannover, Medizinische Hochschule Hannover

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

15 Aug 2022 → 31 Jul 2025

Decision date (initial)

2024-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Biotest AG

External identifiers

EU CT number

2024-513792-41-00

EudraCT number

2021-005362-18

ClinicalTrials.gov

NCT05345990

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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

Secondary objectives 5

1. To analyze the decline of HBsAg during treatment
2. To evaluate the post-treatment HBsAg kinetics/response
3. To determine HBV-DNA levels during and after treatment with hepatitis B immunoglobulins
4. To evaluate the biochemical disease activity (normalization of serum ALT levels)
5. To determine the quality of life (SF-36)

Conditions and MedDRA coding

Chronic hepatitis B

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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 index (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: o combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:  oral  intravaginal  transdermal o 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 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. HBsAg negativity at week 12 of antiviral therapy

Secondary endpoints 5

1. HBsAg decline at weeks 1, 2, 4, 8 and 12 of treatment
2. post-treatment HBsAg negativity up to FU week 24
3. HBV DNA levels during and after hepatitis B immunoglobulin treatment will be reported for each cohort
4. biochemical response (proportion of subjects who reached ALT normalization (ALT ≤ ULN) at week 12 of treatment)
5. quality of life during treatment and follow-up (SF-36)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medizinische Hochschule Hannover

Sponsor organisation

Medizinische Hochschule Hannover

Address

Carl-Neuberg-Strasse 1, Gross Buchholz Gross Buchholz

City

Hanover

Postcode

30625

Country

Germany

Scientific contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology - Clinical trials

Public contact point

Organisation

Medizinische Hochschule Hannover

Contact name

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology - Clinical trials

Third parties 4

Medizinische Hochschule Hannover

Sponsor organisation

Medizinische Hochschule Hannover

Address

Carl-Neuberg-Strasse 1, Gross Buchholz Gross Buchholz

City

Hanover

Postcode

30625

Country

Germany

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications