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Hepatocellular CarcinomaHBIGNCT05293158

Impact of Hepatitis B Immunoglobulins in Patients With Chronic Hepatitis B on Hepatocellular Carcinoma - a Proof of Concept Study

A study testing Hepatect CP 50 I.E./ml infusion solution in people with Hepatocellular Carcinoma and HBV, run by Medical University of Graz.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In the current literature, infection with the hepatitis B virus (HBV) is described as one of the main risk factors for the development of hepatocellular carcinoma (HCC). According to the current study situation, the Hepatitis B surface antigen (HBsAg) is considered as an important marker, since low levels and… Read more about this study

Who is it for?
Ages 19 to 80 years
Conditions the study is for
Hepatocellular Carcinoma, HBV
What is being tested?
Hepatect CP 50 I.E./ml infusion solution
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
No sites listed yet
Study dates
Nov 2024to Jun 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients ≥ 19 years and ≤ 80 of age
  • HBsAg-positive HCC-patients scheduled for resection in ≥6 weeks or HBsAg-positive HCC- patients listed for LT
  • Ability of subjects to understand character and individual consequences of the clinical trial
  • Written informed consent must be available before enrolment in the trial

Who cannot join

  • Clinically significant illness (other than HBV) or any other major medical disorder that, in the opinion of the investigator, may interfere with subject treatment
  • No eligibility for resection / LT
  • Concurrent any other malignancy
  • Co-infection with hepatitis C virus (defined as HCV RNA positive, HCV RNA-negative/anti-HCV-positive patients can be included) and/or human immunodeficiency virus (HIV)
  • Clinical hepatic decompensation
  • Allergy to HBIG
  • Pregnant, lactating patients

Trial locations and contacts

No sites are listed yet.

Peter Schemmer, Univ.-Prof. DDr. MBA FACS contact

+43 316 385 84094

peter.schemmer@medunigraz.at

Judith Kahn, PD Dr. contact

+43 316 385-80676

judith.kahn@medunigraz.at

About this study

Official title: Impact of Hepatitis B Immunoglobulins in Patients With Chronic Hepatitis B on Hepatocellular Carcinoma

In the current literature, infection with the hepatitis B virus (HBV) is described as one of the main risk factors for the development of hepatocellular carcinoma (HCC).

According to the current study situation, the Hepatitis B surface antigen (HBsAg) is considered as an important marker, since low levels and sero-clearance of HBsAg are both correlated with a lower risk of HCC development / recurrence.Currently there is no treatment option available that efficiently targets HBsAg. Besides neutralizing infectious HBV virions, Hepatitis B immunoglobulins (HBIG) can directly bind and neutralize extracellular HBsAg/SVPs, and even intracellular HBsAg targeting is reported. In addition, HBIGs can initiate effector-cell attack (via antibody-dependent cellular cytotoxicity, ADCC) towards infected hepatocytes.

Read more

The potential benefit of HBIGs in the HCC context is further underlined by recent evidence for the ability of HBIGs to reduce the viability, proliferation, and self-renewal of tumor-initiating cells (TICs) - isolated from HBV-HCC patients - accompanied by downregulation of stemness markers, e.g., OCT-4.According to the current study situation, the use of HBIGs significantly reduces the risk of HBV reinfection after transplantation and improves the results of liver transplantation in patients with chronic HBV infection. The potential benefit of treating HBV-HCC patients on the LTx (liver transplantation) waiting list with hepatitis B immunoglobulin is the possible stop or inhibition of tumor progression while waiting for an LTx. So far there is no clinical evidence of this.

Mechanistically, hepatitis B immunoglobulin could occur through neutralization of circulating HBsAg, which is an important driver of an immunosuppressive environment in HBV patients, and possibly through direct effects against HBV HCC tumor cells (through antibody-dependent cellular cytotoxicity, ADCC). Therefore, the idea behind preoperative HBIG administration before liver transplantation is to reduce the rate of patients in whom a transplantation would no longer have been possible due to tumor progression. Thus, due to tumor progression in HBV-positive HCC-patients there is a monthly drop-out from the waiting list of about 4%.

The basic idea behind the treatment of HBV-HCC patients before tumor resection with hepatitis B immunoglobulin is to potentially stop or positively influence tumor progression through the effects mentioned above, in the time between diagnosis and resection.

Zhou et al. (2015) have shown a connection between HBsAg levels and HCC relapses after resection, although the exact role of HBsAg is still unclear. In no case will the treatment postpone the time of tumor resection, as only patients are considered who, for clinical reasons, can expect a certain time until resection. The present proof of concept study aims to quantify HBsAg reduction due to preoperative administration of HBIGs in HBV-positive HCC-patients and serve as a template for future multicentre clinical trials.

Being tested
Hepatect CP 50 I.E./ml infusion solution
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hepatect CP 50 I.E./ml infusion solutionDrug

    Application of i.v. (intravenously) HBIGs for ≥6-weeks:

    Day (D) 0-7: 10.000 IU D14 until end-of-treatment: 10.000 IU once per week HBIGs will be given until LT/liver resection.

Study groups in NCT05293158
Study groupRoleWhat they receive
HBIG treatmentExperimentalNot described
Receives: Drug: Hepatect CP 50 I.E./ml infusion solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HBsAg change from baseline to week 6

    Quantification of the magnitude of the effect of ≥6-week; unit: IU/ml treatment with Hepatitis B immunoglobulins in patients with chronic hepatitis B and HCC, determined by the HBsAg reduction after week 6

    Evaluation of the safety and tolerability of Hepatitis B immunoglobulins administered for ≥6-weeks in patients with chronic hepatitis B and HCC

    Measured: ≥6-weeks

Secondary outcomes (18)

  1. Change of HBsAg at different time points during treatment

    unit: IU/ml

    Measured: baseline and weekly during the treatment period and during the follow-up at 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment stop.

  2. Change of HCC response to treatment

    Tumor size (cm) will be investigated via MR Primovist (RECIST) or alternatively via CT (RECIST).

    Measured: Tumor material will be measured at baseline and at end of treatment (on average ≥6-weeks)

  3. Change of Biochemical response (B cells)

    Immune responses during HBIG treatment (analysis of B cells); unit 10^9/l

    Measured: baseline and weekly during the treatment period and during the follow-up at 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment stop.

  4. Change of Biochemical response (NK cells)

    Immune responses during HBIG treatment (analysis of NK cells); unit 10^9/l

    Measured: baseline and weekly during the treatment period and during the follow-up at 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment stop.

  5. Change of Biochemical response (T cells)

    Immune responses during HBIG treatment (analysis of T cells); unit 10^9/l

    Measured: baseline and weekly during the treatment period and during the follow-up at 2 weeks, 4 weeks, 6 weeks, and 8 weeks after treatment stop.

  6. Change of Cellular response (CD3)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD3); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  7. Change of Cellular response (CD4)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD4); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  8. Change of Cellular response (CD8)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD8); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  9. Change of Cellular response (CD25)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD25); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  10. Change of Cellular response (CD34)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD34); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  11. Change of Cellular response (CD133)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD133); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  12. Change of Cellular response (CD19)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD19); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  13. Change of Cellular response (CD56)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD56); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  14. Change of Cellular response (CD49f)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (CD49f); unit:10^9/L

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  15. Change of Cellular response (FoxP3)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (FoxP3) unit: µg/ml

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  16. Change of Cellular response (Ki67)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (Ki67) unit: %

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  17. Change of Cellular response (HLA-DR)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (HLA-DR) unit: %

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

  18. Change of Cellular response (IFN gamma)

    Tumor material will be collected via liver biopsies and will be analysed by immune histochemistry (IFN gamma) unit: IU/ml

    Measured: Tumor material will be collected at baseline and end-of-treatment (on average ≥6-weeks) via liver biopsies and will be analysed by immune histochemistry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2022
  2. Study startNov 2024 (estimated)
  3. Primary completionJun 2026 (estimated)
  4. Study completionJun 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05293158
Sponsor's protocol ID
HBIG
Acronym
HBIG
Status last verified
Jan 2024
First submitted
14 Mar 2022
Last updated
18 Jan 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Salpini R, Surdo M, Warner N, Cortese MF, Colledge D, Soppe S, Bellocchi MC, Armenia D, Carioti L, Continenza F, Di Carlo D, Saccomandi P, Mirabelli C, Pollicita M, Longo R, Romano S, Cappiello G, Spano A, Trimoulet P, Fleury H, Vecchiet J, Iapadre N, Barlattani A, Bertoli A, Mari T, Pasquazzi C, Missale G, Sarrecchia C, Orecchini E, Michienzi A, Andreoni M, Francioso S, Angelico M, Verheyen J, Ceccherini-Silberstein F, Locarnini S, Perno CF, Svicher V. Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation in vitro. Oncotarget. 2017 Feb 28;8(9):15704-15715. doi: 10.18632/oncotarget.14944.

    PubMed 28152517

  • Liu S, Koh SS, Lee CG. Hepatitis B Virus X Protein and Hepatocarcinogenesis. Int J Mol Sci. 2016 Jun 14;17(6):940. doi: 10.3390/ijms17060940.

    PubMed 27314335

  • Lee EC, Kim SH, Lee SD, Park H, Lee SA, Park SJ. High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation. World J Gastroenterol. 2016 Apr 14;22(14):3803-12. doi: 10.3748/wjg.v22.i14.3803.

    PubMed 27076765

  • Yang Y, Sun JW, Zhao LG, Bray F, Xiang YB. Quantitative evaluation of hepatitis B virus mutations and hepatocellular carcinoma risk: a meta-analysis of prospective studies. Chin J Cancer Res. 2015 Oct;27(5):497-508. doi: 10.3978/j.issn.1000-9604.2015.10.05.

    PubMed 26543337

  • Liu WR, Tian MX, Jin L, Yang LX, Ding ZB, Shen YH, Peng YF, Zhou J, Qiu SJ, Dai Z, Fan J, Shi YH. High levels of hepatitis B surface antigen are associated with poorer survival and early recurrence of hepatocellular carcinoma in patients with low hepatitis B viral loads. Ann Surg Oncol. 2015 Mar;22(3):843-50. doi: 10.1245/s10434-014-4043-5. Epub 2014 Oct 1.

    PubMed 25269529

  • Saab S, Yeganeh M, Nguyen K, Durazo F, Han S, Yersiz H, Farmer DG, Goldstein LI, Tong MJ, Busuttil RW. Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation. Liver Transpl. 2009 Nov;15(11):1525-34. doi: 10.1002/lt.21882.

    PubMed 19877207

  • Lin S, Hoffmann K, Schemmer P. Treatment of hepatocellular carcinoma: a systematic review. Liver Cancer. 2012 Nov;1(3-4):144-58. doi: 10.1159/000343828.

    PubMed 24159579

  • Honer Zu Siederdissen C, Cornberg M. The role of HBsAg levels in the current management of chronic HBV infection. Ann Gastroenterol. 2014;27(2):105-112.

    PubMed 24733569

  • Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH. High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology. 2012 May;142(5):1140-1149.e3; quiz e13-4. doi: 10.1053/j.gastro.2012.02.007. Epub 2012 Feb 11.

    PubMed 22333950

  • Zahner D, Glimm H, Matono T, Churin Y, Herebian D, Mayatepek E, Kohler K, Gattenlohner S, Stinn A, Tschuschner A, Roderfeld M, Roeb E. Hepatitis B virus surface proteins accelerate cholestatic injury and tumor progression in Abcb4-knockout mice. Oncotarget. 2017 Feb 2;8(32):52560-52570. doi: 10.18632/oncotarget.15003. eCollection 2017 Aug 8.

    PubMed 28881751

  • Pollicino T, Cacciola I, Saffioti F, Raimondo G. Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications. J Hepatol. 2014 Aug;61(2):408-17. doi: 10.1016/j.jhep.2014.04.041. Epub 2014 May 5.

    PubMed 24801416

  • Liu H, Xu J, Zhou L, Yun X, Chen L, Wang S, Sun L, Wen Y, Gu J. Hepatitis B virus large surface antigen promotes liver carcinogenesis by activating the Src/PI3K/Akt pathway. Cancer Res. 2011 Dec 15;71(24):7547-57. doi: 10.1158/0008-5472.CAN-11-2260. Epub 2011 Oct 12.

    PubMed 21994334

  • Churin Y, Roderfeld M, Roeb E. Hepatitis B virus large surface protein: function and fame. Hepatobiliary Surg Nutr. 2015 Feb;4(1):1-10. doi: 10.3978/j.issn.2304-3881.2014.12.08.

    PubMed 25713800

  • Li YW, Yang FC, Lu HQ, Zhang JS. Hepatocellular carcinoma and hepatitis B surface protein. World J Gastroenterol. 2016 Feb 14;22(6):1943-52. doi: 10.3748/wjg.v22.i6.1943.

    PubMed 26877602

  • Zhang X, Gao L, Liang X, Guo M, Wang R, Pan Y, Liu P, Zhang F, Guo C, Zhu F, Qu C, Ma C. HBV preS2 transactivates FOXP3 expression in malignant hepatocytes. Liver Int. 2015 Mar;35(3):1087-94. doi: 10.1111/liv.12642. Epub 2014 Aug 8.

    PubMed 25047684

Questions about this trial

What is this clinical trial studying?

A study testing Hepatect CP 50 I.E./ml infusion solution in people with Hepatocellular Carcinoma and HBV, run by Medical University of Graz.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Peter Schemmer, Univ.-Prof. DDr. MBA FACS (+43 316 385 84094, peter.schemmer@medunigraz.at), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HBsAg change from baseline to week 6 (time frame: ≥6-weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05293158, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2024.

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