Chronic Hepatitis BPhase 1/2NCT02881008
Myrcludex B vs Entecavir in Patients With HBeAg Negative Chronic Hepatitis B
A Phase 1/2 study testing Entecavir and Myrcludex B in people with Chronic Hepatitis B, run by Hepatera Ltd. at 9 sites in Russia.
Trial summary
A randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Entecavir and Myrcludex B
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 9 sitesRussia
- Study dates
- 14 Nov 2012to 4 Oct 2014
- 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
- Age 18-65 years inclusive at the time of giving of written informed consent for study participation.
- Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period.
- Liver biopsy performed within one year prior to screening or during screening period.
- Alanine aminotransferase (ALT) ≥1.5 x ULN and ≤ 6 x ULN. If ALT level during screening period is ≥1 ULN the patient can be included in the study after obtaining the sponsor's approval and if the following conditions are met :
- evidence of inflammation such as lymphocyte infiltration confirmed by liver biopsy performed within the 6 months prior to the inclusion in the study,
- and/or the patient has a history of elevated ALT levels of ≥1.5 ULN during the 12 months prior to screening period.
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- HBeAg negative and anti-HBeAg positive.
- HBV DNA ≥ 104 copies/mL.
- 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
- 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).
- Any sign of liver cirrhosis (histological, ultra sound, biochemical).
- Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.
- ALT > 6 ULN.
- Creatinine clearance < 60 mL/min.
- Total bilirubin > 2 mg/dL.
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- Pre-treatment with nucleoside-analogues (lamivudine, telbivudine, entecavir) less than 6 months prior to the first dosing of the investigational medicinal products. Pre-treatment with nucleotide-analogues and interferons is allowed.
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Russia9 sites
SBEI of Higher Professional Education "South Ural State Medical university" of the MoH of the RF
Chelyabinsk, 454052
1-st MMU n.a. I.M. Sechenov based in Moscow State-Owned Health Care Institution "Infectious Clinical Hospital № 2 of Moscow Healthcare Department"
Moscow, 105275
FSBI of Higher Education "People's Friendship University"
Moscow, 117198
FSBHI "Central Clinical Hospital RAS"
Moscow, 119333
LLC "Clinical Hospital of Tsentrosoyuz"
Moscow, 129110
SPb SBHI "The Center for Prevention and Control of AIDS and Infectious Diseases"
Saint Petersburg, 190103
SPb SIH "Clinical Centre of Infectious Diseases Named After S.P. Botkin"
Saint Petersburg, 191167
Medical Company "Hepatolog" LLC
Samara, 430063
SBIH "Stavropol Regional Clinical Hospital"
Stavropol, 355000
About this study
Official title: A Phase 1b/2a Randomized, Open-label Clinical Trial of Daily Myrcludex B Versus Entecavir in Patients With HBeAg Negative Chronic Hepatitis B
A randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B.
Read the detailed description
This is a randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B. Accounting for screen-outs about 76 patients will be screened and 48 of them will be randomized into 6 treatment groups:
Arm A (8 patients): Myrcludex B 0.5 mg / day / sc / 12 weeks Arm B (8 patients): Myrcludex B 1 mg / day / sc / 12 weeks Arm C (8 patients): Myrcludex B 2 mg / day / sc / 12 weeks Arm D (8 patients): Entecavir 0.5 mg / day / orally / 24 weeks Arm E (8 patients): Myrcludex B 5 mg / day / sc / 12 weeks Arm F (8 patients): Myrcludex B 10 mg / day / sc / 24 weeks
The study consists of screening period up to 28 days (Day -28 -1); baseline visit (Day 0), treatment period up to 12 weeks for groups A-C, E and 24 weeks for groups D, F; follow-up period up to 12 weeks for groups A-C, E, F.
- Conditions
- Chronic Hepatitis B
- Being tested
- Entecavir, Myrcludex B
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntecavirDrug
Also called Baraclude®
Myrcludex BDrug
Also called Myrcludex
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Myrcludex B 0.5 mg daily for 12 weeks, followed by 12 weeks follow-up period Receives: Drug: Myrcludex B |
| Arm B | Experimental | Myrcludex B 1 mg daily for 12 weeks, followed by 12 weeks follow-up period Receives: Drug: Myrcludex B |
| Arm C | Experimental | Myrcludex B 2 mg daily for 12 weeks, followed by 12 weeks follow-up period Receives: Drug: Myrcludex B |
| Arm D | Active comparator | Entecavir 0.5 mg daily for 24 weeks Receives: Drug: Entecavir |
| Arm E | Experimental | Myrcludex B 5 mg daily for 12 weeks, followed by 12 weeks follow-up period Receives: Drug: Myrcludex B |
| Arm F | Experimental | Myrcludex B 10 mg daily for 24 weeks, followed by 12 weeks follow-up period Receives: Drug: Myrcludex B |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients With HBsAg Response at 12 Week of Therapy
HBsAg response is defined as serum HBsAg decline of at least 0.5 logs IU/ml (or HBsAg negativation) at week 12 compared to baseline.
Measured: 12 week
Secondary outcomes (6)
Proportion of Patients With HBsAg Response at 24 Week of Therapy
HBsAg response is defined as serum HBsAg decline of at least 0.5 logs IU/ml (or HBsAg negativation) at week 24 compared to baseline.
Measured: 24 weeks
Proportion of Patients With HBV DNA Response at Week 12 of Therapy
HBV DNA response is defined as persistent reduction of HBV DNA by >1 log IU/ml or negativation at week 12 compared to baseline.
Measured: 12 weeks
Proportion of Patients With Biochemical Response at 12 Weeks of Therapy
Biochemical response is defined as normalization of ALT level at week 12 compared to baseline.
Measured: 12 weeks
Proportion of Patients With cccDNA Response at 24 Week of Therapy
Virological cccDNA response is defined as reduction of intrahepatic cccDNA by 0.5 logs in comparison to baseline at week 24.
Measured: 24 weeks
Proportion of Patients With HBV DNA Response at Week 24 of Therapy
HBV DNA response is defined as persistent reduction of HBV DNA by >1 log IU/ml or negativation at week 24 compared to baseline.
Measured: 24 weeks
Proportion of Patients With Biochemical Response at 24 Weeks of Therapy
Biochemical response is defined as normalization of ALT level at week 24 compared to baseline.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2016 (estimated)
- Study start14 Nov 2012
- Primary completion4 Oct 2014
- Study completion4 Oct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hepatera Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pavel Bogomolov, PhD, Principal investigator, LLC "Clinical Hospital of Tsentrosoyuz"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02881008
- Sponsor's protocol ID
- MYR 201 (HBV)
- Status last verified
- Dec 2017
- First submitted
- 18 Aug 2016
- Last updated
- 19 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- 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 14996343Yan 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 23150796Trauner 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 12663868Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available.
PubMed 19714720Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4398-402. doi: 10.1073/pnas.93.9.4398.
PubMed 8633078Yan 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;3. doi: 10.7554/eLife.00049.
PubMed 25409679
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a Randomized, Open-label Clinical Trial of Daily Myrcludex B Versus Entecavir in Patients With HBeAg Negative Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT02881008
- Acronym / sponsor ID
- MYR 201 (HBV)
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Hepatera Ltd.Industry (pharma, biotech, devices)
- Study start
- 14 Nov 2012 (actual)
- Primary completion
- 4 Oct 2014 (actual)
- Study completion
- 4 Oct 2014 (actual)
- First posted
- 26 Aug 2016 (estimated)
- Results
- Posted 19 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B.
Detailed description
This is a randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B. Accounting for screen-outs about 76 patients will be screened and 48 of them will be randomized into 6 treatment groups:
Arm A (8 patients): Myrcludex B 0.5 mg / day / sc / 12 weeks Arm B (8 patients): Myrcludex B 1 mg / day / sc / 12 weeks Arm C (8 patients): Myrcludex B 2 mg / day / sc / 12 weeks Arm D (8 patients): Entecavir 0.5 mg / day / orally / 24 weeks Arm E (8 patients): Myrcludex B 5 mg / day / sc / 12 weeks Arm F (8 patients): Myrcludex B 10 mg / day / sc / 24 weeks
The study consists of screening period up to 28 days (Day -28 -1); baseline visit (Day 0), treatment period up to 12 weeks for groups A-C, E and 24 weeks for groups D, F; follow-up period up to 12 weeks for groups A-C, E, F.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Myrcludex BMyrcludex B 0.5 mg daily for 12 weeks, followed by 12 weeks follow-up period |
| Arm B | Experimental | Drug: Myrcludex BMyrcludex B 1 mg daily for 12 weeks, followed by 12 weeks follow-up period |
| Arm C | Experimental | Drug: Myrcludex BMyrcludex B 2 mg daily for 12 weeks, followed by 12 weeks follow-up period |
| Arm D | Active comparator | Drug: EntecavirEntecavir 0.5 mg daily for 24 weeks |
| Arm E | Experimental | Drug: Myrcludex BMyrcludex B 5 mg daily for 12 weeks, followed by 12 weeks follow-up period |
| Arm F | Experimental | Drug: Myrcludex BMyrcludex B 10 mg daily for 24 weeks, followed by 12 weeks follow-up period |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age 18-65 years inclusive at the time of giving of written informed consent for study participation.
- Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period.
- Liver biopsy performed within one year prior to screening or during screening period.
- Alanine aminotransferase (ALT) ≥1.5 x ULN and ≤ 6 x ULN. If ALT level during screening period is ≥1 ULN the patient can be included in the study after obtaining the sponsor's approval and if the following conditions are met :
- HBeAg negative and anti-HBeAg positive.
Key exclusion criteria (18 listed)
- Decompensated liver disease (Child-Pugh-Score >6).
- Any sign of liver cirrhosis (histological, ultra sound, biochemical).
- Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.
- ALT > 6 ULN.
- Creatinine clearance < 60 mL/min.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntecavirAlso: Baraclude® | Drug | Arm D |
| Myrcludex BAlso: Myrcludex | Drug | Arm A, Arm B, Arm C, Arm E, Arm F |
Primary outcome
Proportion of Patients With HBsAg Response at 12 Week of Therapy
Time frame: 12 week
HBsAg response is defined as serum HBsAg decline of at least 0.5 logs IU/ml (or HBsAg negativation) at week 12 compared to baseline.
6 secondary outcomes
Proportion of Patients With HBsAg Response at 24 Week of Therapy
Time frame: 24 weeks
Proportion of Patients With HBV DNA Response at Week 12 of Therapy
Time frame: 12 weeks
Proportion of Patients With Biochemical Response at 12 Weeks of Therapy
Time frame: 12 weeks
Proportion of Patients With cccDNA Response at 24 Week of Therapy
Time frame: 24 weeks
Proportion of Patients With HBV DNA Response at Week 24 of Therapy
Time frame: 24 weeks
Proportion of Patients With Biochemical Response at 24 Weeks of Therapy
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14996343Lavanchy 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.
- Background: PubMed 23150796Yan 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.
- Background: PubMed 12663868Trauner 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.
- Background: PubMed 19714720Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available.
- Background: PubMed 8633078Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4398-402. doi: 10.1073/pnas.93.9.4398.
- Background: PubMed 25409679Yan 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;3. doi: 10.7554/eLife.00049.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pavel Bogomolov, PhD principal investigator
LLC "Clinical Hospital of Tsentrosoyuz"
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Entecavir and Myrcludex B in people with Chronic Hepatitis B, run by Hepatera Ltd. at 9 sites in Russia.
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 17 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 19 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
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 19 Sep 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?
Proportion of Patients With HBsAg Response at 12 Week of Therapy (time frame: 12 week). 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 NCT02881008, 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 19 Sep 2018.