Myrcludex B vs Entecavir in Patients With HBeAg Negative Chronic Hepatitis B

NCT02881008 | Completed Phase 1 Results

• 1 other identifier: MYR 201 (HBV)
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 9

Brief Summary

A randomized, open-label multicentre clinical trial of daily Myrcludex B versus entecavir in patients with HBeAg negative chronic hepatitis B.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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.

  12 week

Secondary Outcomes (6)

• Proportion of Patients With HBsAg Response at 24 Week of Therapy

  24 weeks

• Proportion of Patients With HBV DNA Response at Week 12 of Therapy

  12 weeks

• Proportion of Patients With Biochemical Response at 12 Weeks of Therapy

  12 weeks

• Proportion of Patients With cccDNA Response at 24 Week of Therapy

  24 weeks

• Proportion of Patients With HBV DNA Response at Week 24 of Therapy

  24 weeks

Study Arms (6)

Arm A

EXPERIMENTAL

Myrcludex B 0.5 mg daily for 12 weeks, followed by 12 weeks follow-up period

Drug: Myrcludex B

Arm B

EXPERIMENTAL

Myrcludex B 1 mg daily for 12 weeks, followed by 12 weeks follow-up period

Drug: Myrcludex B

Arm C

EXPERIMENTAL

Myrcludex B 2 mg daily for 12 weeks, followed by 12 weeks follow-up period

Drug: Myrcludex B

Arm D

ACTIVE COMPARATOR

Entecavir 0.5 mg daily for 24 weeks

Drug: Entecavir

Arm E

EXPERIMENTAL

Myrcludex B 5 mg daily for 12 weeks, followed by 12 weeks follow-up period

Drug: Myrcludex B

Arm F

EXPERIMENTAL

Myrcludex B 10 mg daily for 24 weeks, followed by 12 weeks follow-up period

Drug: Myrcludex B

Interventions

Entecavir DRUG

Also known as: Baraclude®

Arm D

Myrcludex B DRUG

Also known as: Myrcludex

Arm A; Arm B; Arm C; Arm E; Arm F

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :
• and/or the patient has a history of elevated ALT levels of ≥1.5 ULN during the 12 months prior to screening period.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hepatera Ltd.: lead

Study Sites (9)

SBEI of Higher Professional Education "South Ural State Medical university" of the MoH of the RF

Chelyabinsk, 454052, Russia

Location

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, Russia

Location

FSBI of Higher Education "People's Friendship University"

Moscow, 117198, Russia

Location

FSBHI "Central Clinical Hospital RAS"

Moscow, 119333, Russia

Location

LLC "Clinical Hospital of Tsentrosoyuz"

Moscow, 129110, Russia

Location

SPb SBHI "The Center for Prevention and Control of AIDS and Infectious Diseases"

Saint Petersburg, 190103, Russia

Location

SPb SIH "Clinical Centre of Infectious Diseases Named After S.P. Botkin"

Saint Petersburg, 191167, Russia

Location

Medical Company "Hepatolog" LLC

Samara, 430063, Russia

Location

SBIH "Stavropol Regional Clinical Hospital"

Stavropol, 355000, Russia

Location

Related Publications (6)

• 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.

  PMID: 14996343 BACKGROUND

• 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.

  PMID: 23150796 BACKGROUND

• 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.

  PMID: 12663868 BACKGROUND

• Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009 Sep;50(3):661-2. doi: 10.1002/hep.23190. No abstract available.

  PMID: 19714720 BACKGROUND

• Nowak 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.

  PMID: 8633078 BACKGROUND

• 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;3. doi: 10.7554/eLife.00049.

  PMID: 25409679 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; myrcludex-B

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. med. Alexander Alexandrov
• Organization: MYR GmbH

alexandrov@myr-pharma.com

+491777168259

Study Officials

• Pavel Bogomolov, PhD

  LLC "Clinical Hospital of Tsentrosoyuz"

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2016
• First Posted: August 26, 2016
• Study Start: November 14, 2012
• Primary Completion: October 4, 2014
• Study Completion: October 4, 2014
• Last Updated: September 19, 2018
• Results First Posted: September 19, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

RU (9)