Clinical Trials Register

Summary
EudraCT Number:	2016-000395-13
Sponsor's Protocol Code Number:	MYR202
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-02-23
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2016-000395-13

A.3

Full title of the trial

A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination with Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients with Chronic Hepatitis D

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Efficacy and Safety of Myrcludex B in Chronic Hepatitis D

A.3.2

Name or abbreviated title of the trial where available

Myrcludex B in chronic hepatitis D

A.4.1

Sponsor's protocol code number

MYR202

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Hepatera LLC
B.1.3.4	Country	Russian Federation
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Hepatera LLC
B.4.2	Country	Russian Federation
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hepatera LLC
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	12/19 Verkhnyaya Radischevskaya
B.5.3.2	Town/ city	Moscow
B.5.3.3	Post code	109240
B.5.3.4	Country	Russian Federation
B.5.4	Telephone number	7495726-52-53

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/15/1500
D.3 Description of the IMP
D.3.1	Product name	Myrcludex B
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	47-amino acid N-myristoylated lipopeptide
D.3.9.2	Current sponsor code	MXB
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	47-amino acid N-myristoylated lipopeptide
D.3.9.2	Current sponsor code	MXB
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Viread
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TENOFOVIR DISOPROXIL FUMARATE
D.3.9.1	CAS number	202138-50-9
D.3.9.4	EV Substance Code	SUB12607MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	245
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Hepatitis D

E.1.1.1

Medical condition in easily understood language

Chronic Hepatitis D infection

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To investigate the efficacy of MXB and to compare 3 doses of MXB versus observation on background therapy with tenofovir in hepatitis delta patients.

E.2.2

Secondary objectives of the trial

To investigate safety and tolerability, as well as to assess pharmacokinetics and immunogenicity, of three doses of MXB in hepatitis delta patients.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.
2. Positive serum HBsAg for at least 6 months before Screening.
3. Positive serum anti-HDV antibody for at least 6 months.
4. Positive PCR results for serum HDV RNA at Screening.
5. Patients with liver cirrhosis, irrespective of previous interferon treatment .
6. Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) .
7. Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.
8. Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject’s willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment.
9. Negative urine pregnancy test for females of childbearing potential.
10. Inclusion criteria for female subjects:
•Postmenopausal for at least 2 years, or
•Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or
•Abstinence from heterosexual intercourse throughout the study, or
•Willingness to use highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive) throughout the study and for 3 months after the last dose of the study medication.
11. Male subjects must agree to use a highly effective contraception (double barrier method or barrier contraception in combination with hormonal or intrauterine contraceptive used by female partners) and not to donate sperm throughout the study and for 3 months after the last dose of the study medication.

E.4

Principal exclusion criteria

1. Child-Pugh score of B-C or over 6 points.
2. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.
3. Creatinine clearance <60 mL/min.
4. Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study`s Medical Monitor, if such elevation can be clearly attributed to Gilbert’s syndrome associated with low-grade hyperbilirubinemia.
5. Any previous or current malignant neoplasms, including hepatic carcinoma.
6. Systemic connective tissue disorders.
7. NYHA (New York Heart Association) class III-IV congestive heart failure.
8. Patients with uncontrolled arterial hypertension (BP >150/100 mm Hg despite antihypertensive treatment) within 3 months prior to start of clinical phase of the study.
9. Previous or unstable concurrent diseases or conditions that prevent subject’s enrolment into the study.
10. Patients with mental disorders or social circumstances that preclude them from following protocol requirements.
11. Current or previous decompensated liver disease, including coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminaemia, ascites, and esophageal varices hemorrhage.
12. WBC count <3000 cells/mm3.
13. Neutrophil count <1500 cells/mm3.
14. Platelet count <60,000 cells/mm3.
15. Use of prohibited psychotropic agents at Screening.
16. Use of interferons within 30 days before Screening.
17. History of solid organ transplantation.
18. Current alcohol abuse or alcohol abuse within 6 months prior to enrolment in this study.
19. History of disease requiring regular use of systemic glucocorticosteroids.
20. Pregnant or breast-feeding females.
21. Participation in another clinical study within 30 days prior to Screening.
22. Prior treatment with Myrcludex B in previous studies.

E.5 End points

E.5.1

Primary end point(s)

•HDV RNA negativation or decrease by ≥2 log from baseline on Week 24.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24

E.5.2

Secondary end point(s)

•Durability of HDV RNA response to 24 weeks post treatment
•Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24
•Changes in ALT values on Week 24 and Week 48 compared to baseline.
•Lack of fibrosis progression based on transient elastometry (Fibroscan) on Week 24 compared to baseline.
•Changes (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin on Week 24 and Week 48 compared to baseline.
• Changes in HBsAg (decreased levels, disappearance of HBsAg, antibodies to HBsAg) on Week 24 and Week 48 compared to baseline.
• Change in HBV DNA levels on Week 24 and Week 48 compared to baseline.

E.5.2.1

Timepoint(s) of evaluation of this end point

24-48 weeks

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Russian Federation

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

120

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

When patients finish their trial participation, their treating physician will discuss other possible treatments.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-05-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-01-31

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