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

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ClinicalTrials.gov Identifier: NCT02881008
Recruitment Status : Completed
First Posted : August 26, 2016
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
Hepatera Ltd.

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

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: Entecavir Drug: Myrcludex B Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 14, 2012
Actual Primary Completion Date : October 4, 2014
Actual Study Completion Date : October 4, 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Entecavir

Arm Intervention/treatment
Experimental: Arm A
Myrcludex B 0.5 mg daily for 12 weeks, followed by 12 weeks follow-up period
Drug: Myrcludex B
Other Name: Myrcludex

Experimental: Arm B
Myrcludex B 1 mg daily for 12 weeks, followed by 12 weeks follow-up period
Drug: Myrcludex B
Other Name: Myrcludex

Experimental: Arm C
Myrcludex B 2 mg daily for 12 weeks, followed by 12 weeks follow-up period
Drug: Myrcludex B
Other Name: Myrcludex

Active Comparator: Arm D
Entecavir 0.5 mg daily for 24 weeks
Drug: Entecavir
Other Name: Baraclude®

Experimental: Arm E
Myrcludex B 5 mg daily for 12 weeks, followed by 12 weeks follow-up period
Drug: Myrcludex B
Other Name: Myrcludex

Experimental: Arm F
Myrcludex B 10 mg daily for 24 weeks, followed by 12 weeks follow-up period
Drug: Myrcludex B
Other Name: Myrcludex




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Proportion of Patients With HBsAg Response at 24 Week of Therapy [ Time Frame: 24 weeks ]
    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.

  2. Proportion of Patients With HBV DNA Response at Week 12 of Therapy [ Time Frame: 12 weeks ]
    HBV DNA response is defined as persistent reduction of HBV DNA by >1 log IU/ml or negativation at week 12 compared to baseline.

  3. Proportion of Patients With Biochemical Response at 12 Weeks of Therapy [ Time Frame: 12 weeks ]
    Biochemical response is defined as normalization of ALT level at week 12 compared to baseline.

  4. Proportion of Patients With cccDNA Response at 24 Week of Therapy [ Time Frame: 24 weeks ]
    Virological cccDNA response is defined as reduction of intrahepatic cccDNA by 0.5 logs in comparison to baseline at week 24.

  5. Proportion of Patients With HBV DNA Response at Week 24 of Therapy [ Time Frame: 24 weeks ]
    HBV DNA response is defined as persistent reduction of HBV DNA by >1 log IU/ml or negativation at week 24 compared to baseline.

  6. Proportion of Patients With Biochemical Response at 24 Weeks of Therapy [ Time Frame: 24 weeks ]
    Biochemical response is defined as normalization of ALT level at week 24 compared to baseline.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65 years inclusive at the time of giving of written informed consent for study participation.
  2. Chronic hepatitis B defined by the presence of HBsAg for at least 6 months prior to screening period.
  3. Liver biopsy performed within one year prior to screening or during screening period.
  4. 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.
  5. HBeAg negative and anti-HBeAg positive.
  6. HBV DNA ≥ 104 copies/mL.
  7. All women of childbearing potential must have a negative urine pregnancy test prior to enrolment.
  8. 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.
  9. 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.
  10. An understanding, ability and willingness to fully comply with study procedures and restrictions.
  11. An ability to provide the written informed consent to participate in the study.

Exclusion Criteria:

  1. Decompensated liver disease (Child-Pugh-Score >6).
  2. Any sign of liver cirrhosis (histological, ultra sound, biochemical).
  3. Co-infected with hepatitis C virus (HCV), hepatitis D virus (HDV), or HIV.
  4. ALT > 6 ULN.
  5. Creatinine clearance < 60 mL/min.
  6. Total bilirubin > 2 mg/dL.
  7. 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.
  8. 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.
  9. 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.
  10. History of clinically evident pancreatitis.
  11. 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.
  12. Participation in another study with an investigational drug within less than one month prior to this study or simultaneously to this study.
  13. Patients who are unable or unwilling to follow the protocol requirements.
  14. Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator.
  15. Patients with limited mental capacity to the extent that she/he cannot provide informed consent or information regarding adverse events of the study drug.
  16. Clinically significant renal, respiratory or cardiovascular disease.
  17. Pregnancy and lactation.
  18. Patients who have previously participated in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02881008


Locations
Russian Federation
SBEI of Higher Professional Education "South Ural State Medical university" of the MoH of the RF
Chelyabinsk, Russian Federation, 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, Russian Federation, 105275
FSBI of Higher Education "People's Friendship University"
Moscow, Russian Federation, 117198
FSBHI "Central Clinical Hospital RAS"
Moscow, Russian Federation, 119333
LLC "Clinical Hospital of Tsentrosoyuz"
Moscow, Russian Federation, 129110
SPb SBHI "The Center for Prevention and Control of AIDS and Infectious Diseases"
Saint Petersburg, Russian Federation, 190103
SPb SIH "Clinical Centre of Infectious Diseases Named After S.P. Botkin"
Saint Petersburg, Russian Federation, 191167
Medical Company "Hepatolog" LLC
Samara, Russian Federation, 430063
SBIH "Stavropol Regional Clinical Hospital"
Stavropol', Russian Federation, 355000
Sponsors and Collaborators
Hepatera Ltd.
Investigators
Principal Investigator: Pavel Bogomolov, PhD LLC "Clinical Hospital of Tsentrosoyuz"

Publications:
Responsible Party: Hepatera Ltd.
ClinicalTrials.gov Identifier: NCT02881008     History of Changes
Other Study ID Numbers: MYR 201 (HBV)
First Posted: August 26, 2016    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents