Clinical Trials Register

Summary
EudraCT Number:	2014-001400-22
Sponsor's Protocol Code Number:	GS-US-283-1059
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-10-07
Trial results	View 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

Netherlands - Competent Authority

A.2

EudraCT number

2014-001400-22

A.3

Full title of the trial

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects with Chronic Hepatitis B

A.3.1

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

A study looking at the safety and effectiveness of treatment with GS-9620 for patients with chronic Hepatitis B infection who are already receiving treatment for their infection

A.4.1

Sponsor's protocol code number

GS-US-283-1059

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02166047

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	Gilead Sciences, Inc.
B.1.3.4	Country	United States
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	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences, Inc.
B.5.2	Functional name of contact point	Medical Monitor
B.5.3	Address:
B.5.3.1	Street Address	333 Lakeside Drive
B.5.3.2	Town/ city	Foster City
B.5.3.3	Post code	CA 94404
B.5.3.4	Country	United States
B.5.4	Telephone number	+1650574 3000
B.5.5	Fax number	+1650578 9264
B.5.6	E-mail	clinical.trials@gilead.com

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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GS-9620
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	GS-9620
D.3.9.2	Current sponsor code	GS-9620
D.3.9.4	EV Substance Code	SUB166250
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	1
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	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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GS-9620
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	GS-9620
D.3.9.2	Current sponsor code	GS-9620
D.3.9.4	EV Substance Code	SUB166250
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: 3
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GS-9620
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	GS-9620
D.3.9.2	Current sponsor code	GS-9620
D.3.9.4	EV Substance Code	SUB166250
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	4
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Chronic Hepatitis B (CHB) Infection

E.1.1.1

Medical condition in easily understood language

Hepatitis B

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10008910
E.1.2	Term	Chronic hepatitis B
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objectives of this study are:
•To evaluate the safety and tolerability of GS-9620 in subjects with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV)
•To evaluate the efficacy of GS-9620 at Week 24 measured by the change from Baseline (BL) in serum hepatitis B s antigen (HBsAg log10 IU/ml) levels

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are:
• To evaluate the rates of HBsAg loss and seroconversion at Weeks 24 and 48
• To evaluate the rates of hepatitis B e antigen (HBeAg) loss and seroconversion at Weeks 24 and 48
• To evaluate the change in log10 IU/ml serum HBsAg from Baseline to Weeks 4, 8, 12 and 48
• To evaluate the proportion of subjects with serum HBsAg decline ≥ 1 log10 IU/ml at Weeks 4, 8, 12, 24 and 48
• To evaluate the proportion of subjects experiencing Hepatitis B virus (HBV) virologic breakthrough
• To evaluate the incidence of drug resistance mutations

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenomic (PG) Sub-study for Additional PG Analyses
All subjects will be eligible to participate in the pharmacogenomics (PG) sub-study. For subjects who provide separate consent for this optional genetic testing, an additional blood sample will be obtained. This sample is recommended to be collected at the Baseline/Day 1 visit, but may be collected at any time during the study or at a separate poststudy visit, if necessary.

Liver Substudy
Approximately ten additional subjects (in addition to the 150 initially planned) will participate in the Liver Substudy. The ten subjects will be randomized in a 1:3:3:3 ratio to placebo or one of the following doses of GS-9620 : 1, 2 or 4 mg for 8 weekly doses. Upon consent, fine needle aspirate liver biopsy samples will be collected at Baseline and Study Visit Week 7 + 24 hours, to determine effect of GS-9620 on the liver cell populations. Additionally whole blood samples for lymphophenotyping and RNA evaluation will be obtained at Baseline and at Study Visit Week 7 + 24 Hours.

E.3

Principal inclusion criteria

1. Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
2. Adult male and non-pregnant, non-lactating female subjects, 18–65 years of age inclusive
3. A negative serum pregnancy test is required for female subjects
4. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
5. Documented evidence of chronic HBV infection with detectable HBsAg levels at screening
6. Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below LLOQ 6 or more months prior to screening, and HBV DNA < 20 IU/ml at screening
7. Subjects currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
8. Willing to provide blood sample for TLR-7 and IL28B SNP assessment
9. Must be willing and able to comply with all study requirements

E.4

Principal exclusion criteria

1. Extensive bridging fibrosis or cirrhosis
3. Co-infection with HIV, hepatitis C virus (HCV) or hepatitis D virus (HDV)
4. Evidence of hepatocellular carcinoma
5. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection.
6. Significant cardiovascular, pulmonary, or neurological disease
7. Any of the conditions described in the protocol that may worsen in response to IFN
8. Chronic liver disease of a non-HBV etiology
9. Received solid organ or bone marrow transplant
10. Received prolonged therapy with immunomodulators or biologics within 3 months of screening
11. Use of another investigational agents within 3 months of screening, unless allowed by the Sponsor
12. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance
13. Known hypersensitivity to study drug, metabolites or formulation excipients
14. Screening electrocardiogram (ECG) with clinically significant abnormalities and with QTcF interval ≥ 450 msec for males and ≥ 470 msec for females
15. Women who may wish to become pregnant during the course of the study
16. Male subjects unwilling to refrain from sperm donation for at least 90 days after the last dose of study drug
17. Use of any prohibited con-medications as described in the protocol

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is:
• The mean change in serum HBsAg (log10 IU/ml) from Baseline to Week 24

E.5.1.1

Timepoint(s) of evaluation of this end point

24 weeks after cessation of therapy

E.5.2

Secondary end point(s)

Secondary endpoints are:
• The proportion of subjects with HBsAg loss and seroconversion at Weeks 24 and 48
• The proportion of subjects with HBeAg loss and seroconversion at Weeks 24 and 48
• The mean change in log10 IU/ml serum HBsAg at Weeks 4, 8, 12 and 48
• The proportion of subjects with ≥ log10 decline in serum HBsAg titers from Baseline at Weeks 4, 8, 12, 24 and 48
• The proportion of subjects with breakthrough ( HBV DNA > 69 IU/ml with confirmation > 2 weeks after the initial test in the setting of satisfactory adherence to treatment with OAV) through Week 48
• The proportion of subjects with drug resistance mutations at Week 48

E.5.2.1

Timepoint(s) of evaluation of this end point

4, 8, 24 and 48 weeks after cessation of therapy

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

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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)

E.8.2.2

Placebo

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

Canada

Italy

Korea, Republic of

Netherlands

New Zealand

United States

E.8.7

Trial has a data monitoring committee

Yes

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

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

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:

156

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

160

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)

All subjects will be eligible for enrollment in the HBsAg Registry Study, provided this study is approved and available at the subject's site. The purpose of the HBsAg Registry Study will be to evaluate the long-term effect of GS-9620 on HBsAg decline and/or loss for up to 3 years post-treatment.

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

2014-10-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-01-15

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-20

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