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Chronic Hepatitis D InfectionPhase 1/2NCT02637999

Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative HBV/HDV Co-infection

A Phase 1/2 study testing PEG IFN alfa-2a and Myrcludex B in people with Chronic Hepatitis D Infection, run by Hepatera Ltd..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Randomized open-label substudy of daily Myrcludex B (MXB) plus pegylated interferon-alpha-2a (PEG-INF-a) in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B virus (HBV) co-infected with hepatitis delta virus (HDV). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Chronic Hepatitis D Infection
What is being tested?
PEG IFN alfa-2a and Myrcludex B
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
No sites listed yet
Study dates
13 Feb 2014to 21 Jan 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period. Co-infection with hepatitis D virus defined as positive anti-HDV antibodies for at least 3 months and positive for HDV-RNA within the screening period.
  • Liver biopsy performed within one year prior to screening or during screening period.
  • HBeAg negative
  • All women of childbearing potential must have a negative urine pregnancy test prior to enrolment.
  • Women must:
  • Be menopausal for at least 2 years, or
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  • Be surgically sterile (total hysterectomy or bilateral ovariectomy or bilateral tubal ligation/clips or otherwise be incapable of pregnancy), or
  • Not be heterosexually active during the study, or
  • Agree to use a highly effective method of birth control (double barrier method or combination of barrier method with hormonal or intrauterine device) during the study and for 3 month after the last dosing of the investigational medicinal product.
  • Men must agree to use a highly effective method of birth control (double barrier methods or combination of barrier method with hormonal or intrauterine device in their women-partner) and not to donate a sperm during the study and for 3 month after the last dosing of the investigational medicinal product.
  • An understanding, ability and willingness to fully comply with study procedures and restrictions.
  • An ability to provide the written informed consent to participate in the study

Who cannot join

  • Decompensated liver disease (Child-Pugh-Score >6).
  • Co-infected with hepatitis C virus (HCV), or HIV.
  • Patients with presence of anti-HCV antibody and negative HCV RNA in two separate occasions within 12 months prior to screening could be enrolled into the study after sponsor written permission.
  • ALT > 6 ULN.
  • Creatinine clearance < 60 mL/min.
  • Total bilirubin > 2 mg/dL.
Show all 18Show fewer
  • Confirmed contraindication for treatment with PEG-INF-a.
  • History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein (AFP) levels. In patients with such findings, HCC will be ruled-out prior to screening for the present study.
  • One or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, e.g. congestive heart failure or other severe cardiopulmonary disease). Patients with Gilbert's syndrome and Dubin-Johnson syndrome, two benign disorders associated with low-grade hyperbilirubinemia can be enrolled into the trial.
  • History of clinically evident pancreatitis.
  • History of alcohol or drug abuse within the preceding two years. For the purposes of the present study, alcohol abuse is arbitrarily defined as frequent consumption of alcoholic beverages with an average daily intake of more than 40 g of ethanol.
  • Participation in another study with an investigational drug within less than one month prior to this study or simultaneously to this study.
  • Patients who are unable or unwilling to follow the protocol requirements.
  • Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator.
  • Patients with limited mental capacity to the extent that she/he cannot provide informed consent or information regarding adverse events of the study drug.
  • Clinically significant renal, respiratory or cardiovascular disease.
  • Pregnancy and lactation.
  • Patients who have previously participated in this study.

About this study

Official title: Randomized Open-label Substudy of Daily Myrcludex B Plus Pegylated Interferon-alpha-2a in Patients With HBeAg Negative Chronic Hepatitis B Co-infected With Hepatitis Delta

Randomized open-label substudy of daily Myrcludex B (MXB) plus pegylated interferon-alpha-2a (PEG-INF-a) in patients with hepatitis B e antigen (HBeAg) negative chronic hepatitis B virus (HBV) co-infected with hepatitis delta virus (HDV).

Read the detailed description

The study is designed to evaluate safety and efficacy of MXB in a subset of HBV infected patients who are co-infected with HDV. Hepatitis delta represents the most severe form of chronic viral hepatitis and there is no approved treatment option available for patients infected with both HBV and HDV.

24 patients will be randomised into 3 arms: pre-treatment with MXB followed by PEG-INF-a treatment versus a combination of both drugs versus PEG-INF-a.

Prolonged blockade of HBV entry into hepatocytes should also block infection with HDV particles (which uses hepatitis B surface antigen (HBsAg) as its envelope) and thus provide a therapeutic option for this otherwise hardly treatable disease. PEG-INF-a is used for the treatment of chronic hepatitis delta. The study endpoints are virological response (HBsAg, hepatitis delta virus ribonucleic acid (HDV RNA), hepatitis B virus deoxyribonucleic acid (HBV DNA)), as well as safety and tolerability and drug immunogenicity.

Being tested
PEG IFN alfa-2a, Myrcludex B

What participants receive

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

  • PEG IFN alfa-2aDrug

    Also called Pegasys

  • Myrcludex BDrug

    Also called Myrcludex

Study groups in NCT02637999
Study groupRoleWhat they receive
MXB then PEG IFNExperimentalMyrcludex B 2mg daily for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 48 weeks
Receives: Drug: PEG IFN alfa-2a; Drug: Myrcludex B
MXB + PEG IFN then PEG IFNExperimentalMyrcludex B 2mg daily and PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks, followed by PEG IFN alfa-2a 180 µg/0.5 mL weekly for 24 weeks
Receives: Drug: PEG IFN alfa-2a; Drug: Myrcludex B
PEG IFNActive comparatorPEG IFN alfa-2a 180 µg/0.5 mL once weekly for 48 weeks
Receives: Drug: PEG IFN alfa-2a

What is being measured

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

  1. Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 12 of Therapy

    HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 12 compared to baseline (including the patient with negative baseline level)

    Measured: Baseline and 12 weeks

Secondary outcomes (8)

  1. Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 24 of Therapy

    HBsAg response was defined as serum HBsAg decline of at least 0.5 log IU/mL (or HBsAg negativation) at week 24 compared to baseline (including the patient with negative baseline level)

    Measured: Baseline and 24 weeks

  2. Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 24 of Therapy

    HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

    Measured: Baseline and 24 weeks

  3. Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Response at Week 12 of Therapy

    HBV DNA response was defined as persistent reduction of HBV DNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

    Measured: Baseline and 12 weeks

  4. Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 12 of Therapy

    HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

    Measured: Baseline and 12 weeks

  5. Number of Participants With Hepatitis D Virus Ribonucleic Acid (HDV RNA) Response at Week 24 of Therapy

    HDV RNA response was defined as persistent reduction of HDV RNA by > 1 log IU/mL or negativation (including the patient with negative baseline level)

    Measured: Baseline and 24 weeks

  6. Number of Participants With Biochemical Response at Week 12 of Therapy

    Biochemical response was defined as normalization of ALT level as compared to baseline.

    Measured: Baseline and 12 weeks

  7. Number of Participants With Biochemical Response at Week 24 of Therapy

    Biochemical response was defined as normalization of ALT level as compared to baseline.

    Measured: Baseline and 24 weeks

  8. Number of Participants With Covalently Closed Circular Deoxyribonucleic Acid (cccDNA) Response at Week 72 of Therapy

    Virological cccDNA response was defined as reduction of intrahepatic cccDNA by 0.5 log in comparison to baseline at the end of follow up.

    Measured: Baseline and 72 weeks for arm A and 48 weeks for arms B and C

Timeline

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

  1. First posted22 Dec 2015 (estimated)
  2. Study start13 Feb 2014
  3. Primary completion21 Jan 2016
  4. Study completion21 Jan 2016

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02637999
Sponsor's protocol ID
MYR 201 (HDV)
Status last verified
Apr 2018
First submitted
17 Dec 2015
Last updated
13 Apr 2018
Data monitoring committee
No
Individual data sharing
No

Publications

  • Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004 Mar;11(2):97-107. doi: 10.1046/j.1365-2893.2003.00487.x.

    PubMed 14996343

  • Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife. 2012 Nov 13;1:e00049. doi: 10.7554/eLife.00049.

    PubMed 23150796

  • Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003 Apr;83(2):633-71. doi: 10.1152/physrev.00027.2002.

    PubMed 12663868

  • Romeo R, Del Ninno E, Rumi M, Russo A, Sangiovanni A, de Franchis R, Ronchi G, Colombo M. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009 May;136(5):1629-38. doi: 10.1053/j.gastro.2009.01.052. Epub 2009 Jan 29.

    PubMed 19208358

  • Cornberg M, Protzer U, Dollinger MM, Petersen J, Wedemeyer H, Berg T, Jilg W, Erhardt A, Wirth S, Schirmacher P, Fleig WE, Manns MP. Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the German guidelines for the management of HBV infection. Z Gastroenterol. 2007 Dec;45(12):1281-328. doi: 10.1055/s-2007-963714. No abstract available.

    PubMed 18080231

  • Blank A, Markert C, Hohmann N, Carls A, Mikus G, Lehr T, Alexandrov A, Haag M, Schwab M, Urban S, Haefeli WE. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex B. J Hepatol. 2016 Sep;65(3):483-9. doi: 10.1016/j.jhep.2016.04.013. Epub 2016 Apr 27.

    PubMed 27132172

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PEG IFN alfa-2a and Myrcludex B in people with Chronic Hepatitis D Infection, run by Hepatera Ltd..

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 12 inclusion and 18 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: finished, as of the sponsor's last update on 13 Apr 2018. 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.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Hepatitis B Surface Antigen (HBsAg) Response at Week 12 of Therapy (time frame: Baseline and 12 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 NCT02637999, which also lists 6 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 13 Apr 2018.

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