Clinical Trials Register

Summary
EudraCT Number:	2021-003567-10
Sponsor's Protocol Code Number:	217023
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Temporarily Halted
Date on which this record was first entered in the EudraCT database:	2021-11-03
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 - PEI

A.2

EudraCT number

2021-003567-10

A.3

Full title of the trial

A phase 2, single-blinded, randomised, controlled multi-country study to evaluate the safety, reactogenicity, efficacy and immune response following sequential treatment with an anti-sense oligonucleotide (ASO) against chronic Hepatitis B (CHB) followed by chronic Hepatitis B targeted immunotherapy (CHB-TI) in CHB patients receiving nucleos(t)ide analogue (NA) therapy.

A.3.1

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

A study on the safety, efficacy and immune response following sequential treatment with an anti-sense oligonucleotide against chronic Hepatitis B (CHB) and chronic Hepatitis B targeted immunotherapy (CHB-TI) in CHB patients receiving nucleos(t)ide analogue (NA) therapy.

A.3.2

Name or abbreviated title of the trial where available

TH HBV ASO-001

A.4.1

Sponsor's protocol code number

217023

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	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
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	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l’Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.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	GSK3228836
D.3.2	Product code	GSK3228836
D.3.4	Pharmaceutical form	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	Bepirovirsen
D.3.9.1	CAS number	1403787-62-1
D.3.9.3	Other descriptive name	GSK3228836A
D.3.9.4	EV Substance Code	SUB208554
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	TH HBV adjuvanted recombinant proteins vaccine (80-80)
D.3.2	Product code	HBc-HBs/AS01B-4 80-80 vaccine component
D.3.4	Pharmaceutical form	Powder and suspension for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	HBc
D.3.9.3	Other descriptive name	Recombinant HBV proteins HBc
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	HBs
D.3.9.3	Other descriptive name	Recombinant HBV proteins HBs
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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	TH HBV MVA-HBV 2x10e8 pfu vaccine component
D.3.2	Product code	MVA-HBV 2x10e8 pfu
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	MVA-HBV
D.3.9.3	Other descriptive name	Modified Vaccinia Ankara HBV vaccine
D.3.10	Strength
D.3.10.1	Concentration unit	PFU plaque forming unit
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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: 4
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	TH HBV ChAd155-hli-HBV 5x10e10 vp vaccine component
D.3.2	Product code	ChAd155-hli-HBV 5x10e10 vp
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	ChAd155-hIi-HBV
D.3.9.3	Other descriptive name	Chimpanzee adenovirus HBV vaccine
D.3.10	Strength
D.3.10.1	Concentration unit	Vector genome
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50000000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hepatitis B virus (HBV) infection

E.1.1.1

Medical condition in easily understood language

HBV infection, especially chronic infection, is a significant worldwide medical problem that affects the liver.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10019731
E.1.2	Term	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

Safety
• To assess the safety of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection stable on NA therapy.
Efficacy
• To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection stable on NA therapy.
• To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A in comparison with GSK3228836 treatment in participants with CHB infection stable on NA therapy.

E.2.2

Secondary objectives of the trial

Safety
• To assess the safety of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection stable on NA therapy.
Efficacy
• To assess the efficacy of sequential treatment with GSK3228836 and GSK3528869A in comparison with baseline in participants with CHB infection who are virally suppressed on NA therapy.
• To describe durability of Sustained Virologic Response (SVR)
Immunogenicity
• To assess the humoral and cellular immune responses specific to HBs and HBc antigens of sequential treatment with GSK3228836 and GSK3528869A in participants with CHB infection who are virally suppressed on NA therapy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Participants, who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
• A male or female between, and including, 18 and 65 years of age at the time of signing of the informed consent (except for South Korea, where a male or female between, and including, 19 and 65 years of age at the time of signing of the informed consent can participate in the study).
• Participants who are Hepatitis B envelop antigen (HBeAg) positive or negative.
• Participants who have documented chronic HBV infection ≥6 months prior to screening and currently receiving stable NA therapy defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study.
• CHB patient, under and adherent to treatment with a NA with high barrier to resistance (e.g. entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide).
• Participants with ALT ≤ 2x upper limit of normal (ULN) documented in approximately the last 6 months (i.e., no ALT >2x ULN).
• Participants with plasma or serum HBsAg concentration >100 IU/mL.
• Participants must be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL.
• A male participant is eligible if he agrees to the following during the intervention period and for at least 90 days after the last dose of study intervention
- Refrain from donating sperm
- AND be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below
o Agree to use a male condom [and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak] when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant
• A female participant is eligible:
- If she is not pregnant or breastfeeding
- AND at least one of the following conditions applies:
o Is not a WOCBP
o Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for at least 90 days after the last dose of study treatment.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.

E.4

Principal exclusion criteria

Medical conditions
•Clinically significant abnormalities, aside from chronic HBV infection
•Co-infection with: Current or past history of HCV,HIV,HDV
•History of or suspected liver cirrhosis and/or evidence of cirrhosis as determined by
-both AST-Platelet Index (APRI) >2 and FibroSure/FibroTest result >0.7
-Liver biopsy (METAVIR Score F4) or Liver stiffness >12 kPa
•FibroScan TE score >9.6 kPa and FibroTest score >0.59 at Screening
•Diagnosed or suspected HCC
•History of
-malignancy within the past 5 years except of specific
cancers that are cured by surgical resection
-vasculitis or presence of symptoms and signs of potential vasculitis
-extrahepatic disorders possibly related to HBV immune conditions
•Positive (or borderline positive) ANCA at screening
•Low C3/C4 at screening AND evidence of past history or current manifestations of vasculitic/inflammatory/autoimmune conditions
•History of alcohol or drug abuse/dependence
•QTcF ≥450 msec
•Laboratory results as follows:
-Serum albumin<3.5 g/dL
-GFR<60 mL/min/1.73m^2
-INR>1.25
-PLT count<140x10^9/L
-HGB<10 g/dl
-T Bil>1.25xULN unless considered as clinically not significant by the Investigator
-ACR≥0.03 mg/mg
•Medical history of hepatic decompensation
•Planned or previous liver transplantation
•Documented evidence of other currently active cause of hepatitis
•Any other clinical condition that might pose additional risk to the participant due to participation in the study
•Major congenital defects
•Recurrent history or uncontrolled neurological disorders or seizures
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention(s)
Prior/Concomitant therapy
•Use of any investigational or non-registered product other than the study interventions within 30 days before the first dose of study interventions, or their planned use during the study
•Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which may have activity against HBV within 6 months (M) prior the study
•Currently taking, or took within 12 M of screening, any interferon-containing therapy
•Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 M, except for adenovirus/adenovector-based COVID-19 vaccines that could be administered up to 30 days prior to the first study vaccine dose (applicable for all patients except for the patients in France) OR Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 M (applicable for the patients in France only)
•Planned administration/administration of a vaccine not foreseen by the study protocol within 14 days before the first dose and/or 30 days after the last dose of study intervention administration, with the exception of influenza vaccine that may be given at any time except within a 7-day period before or after each dose and COVID-19 vaccine that may be given at any time except within a 30-day period before or after each vaccine dose apart from COVID-19 mRNA based-vaccines that may be administered any time except for the period of 14 days before and 30 days after each study vaccine dose
•Administration of:
-long-acting immune-modifying drugs at any time during the study
-immunoglobulins and/or any blood products or plasma derivatives
within 3 M before the first dose of study interventions or planned administration during the study
•Chronic administration of immunosuppressants or other immune-modifying drugs within 3 M prior to the first study intervention (e.g. prednisone equivalent ≥20 mg/day; ≥10 mg/day applicable in Germany only). Inhaled and topical steroids are allowed
•Participants for whom immunosuppressive treatment is not advised
•Treatment with nephrotoxic drugs or competitors of renal excretion within 2 M prior to Screening or planned during the study
•Participants requiring anti-coagulation therapies
Prior/Concurrent clinical study experience
•Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention
•Previous participation in clinical trials with administration of either GSK3228836 or GSK3528869A
•Previous participation in a clinical study in which he/she has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days
•Prior treatment with any other oligonucleotide or siRNA within 12 M prior to the first dosing day
Other exclusions
•Pregnant or lactating female
•Female planning to become pregnant/to discontinue contraceptive precautions
•Any study personnel or their immediate dependents, family, or household members
•History of/sensitivity to GSK3228836, or components thereof, or a history of drug or other allergy that contraindicates their participation

E.5 End points

E.5.1

Primary end point(s)

1. Percentage of participants reporting any grade 3 adverse event (AE) from first dose of GSK3228836 up to study end
2. Percentage of participants reporting any serious adverse event (SAE) from first dose of GSK3228836 up to study end
3. Percentage of participants reporting any adverse events of special interest (AESIs) grade 3 or higher from first dose of GSK3228836 up to study end
4. Percentage of participants who achieve sustained virologic response (SVR) for 24 weeks after the planned end of active treatment in the absence of rescue medication, and difference between treatment arms (corresponding to GSK3228836 regimens)

E.5.1.1

Timepoint(s) of evaluation of this end point

1. From first dose of GSK3228836 (Treatment 1 [T1]-Day[D]1) up to study end (Treatment 2 [T2]-D841)
2, 3. From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 841)
4. For up to 24 weeks after the planned end of active treatment (planned end of active treatment = Treatment 1-Day 78 for ASO12 group, Treatment 1-Day 162 for ASO24 group and Treatment 2-Day 169 for ASO12-TI and ASO24-TI groups)

E.5.2

Secondary end point(s)

* Percentage of participants
1. * reporting each solicited administration site event post-
GSK3528869A study intervention administration
2. * reporting each solicited systemic event post-GSK3528869A study
intervention administration
3. * reporting any unsolicited AE post-GSK3528869A study intervention administration
4. * reporting any AE from first dose of GSK3228836 up to study end
5. * reporting any AESIs from first dose of GSK3228836 up to study end
6. * reporting any pIMDs from first dose of GSK3528869A up to study end
7. * reporting hematological, biochemical or urinalysis laboratory
abnormalities at pre-defined time points during T1 period
8. * reporting hematological, biochemical or urinalysis laboratory
abnormalities at pre-defined time points during T2 period
9. * reporting hematological, biochemical or urinalysis laboratory
abnormalities at pre-defined time points during follow-up period
10. * who achieve quantitative Hepatitis B surface antigen assessment
(qHBsAg) decrease & HBsAg loss at pre-defined time points from
GSK3228836 baseline (T1-D1) up to end of treatment period
11. * who achieve qHBsAg decrease & HBsAg loss at pre-defined time
points from GSK3228836 baseline (T1-D1) up to end of T1 period
12. * who achieve qHBsAg decrease & HBsAg loss at pre-defined time
points from GSK3528869A/control baseline (T2-D1) up to end of T2
period
13. Changes in qHBsAg at pre-defined time points from GSK3228836
baseline (T1-D1) up to end of treatment period
14. Changes in qHBsAg at pre-defined time points from GSK3228836
baseline (T1-D1) up to end of T1 period
15. Changes in qHBsAg at pre-defined time points from
GSK3528869A/control baseline (T2-D1) up to end of T2 period
16. * in ASO24-TI & ASO24 groups with HBsAg loss & anti-HBs
seroconversion
17. * in ASO12-TI & ASO12 groups with HBsAg loss & anti-HBs
seroconversion
18. Geometric mean concentrations (GMCs) of qHBsAg for participants in ASO24-TI & ASO24 groups
19. Geometric mean concentrations (GMCs) of qHBsAg for participants in ASO12-TI & ASO12 groups
20. Duration of SVR in terms of time to the first occurrence of HBsAg
reversion and/or HBV DNA reversion
21. * in ASO24-TI & ASO24 groups who experienced HBV DNA virologic
breakthrough
22. * in ASO12-TI & ASO12 groups who experienced HBV DNA virologic
breakthrough
23. * with anti-HBc antibody response
24. Anti-HBc antibody concentrations
25. * who achieved HBsAg seroconversion
26. * with anti-HBs antibody response
27. Anti-HBs antibody concentrations
28. * with anti-HBs antibody concentrations ≥10 mIU/mL
29. * with anti-HBs antibody concentrations ≥100 mIU/mL
30. Frequency of HBc-specific CD4+ T-cells
31. Frequency of HBs-specific CD4+ T-cells
32. Frequency of HBc-specific CD8+ T-cells
33. Frequency of HBs-specific CD8+ T-cells
34. Number of HBc- & HBs-specific CD4+ T cells responders
35. Number of HBc- & HBs-specific CD8+ T cells responders
Timeframes:
1,2. Within 7 days post-administration (day of administration + 6
subsequent days) of each dose of GSK3528869A study intervention
3. Within 30 days post-administration (day of administration + 29
subsequent days) of each dose of GSK3528869A study intervention
4,5. From first dose of GSK3228836 (Treatment 1-Day 1) up to study end (Treatment 2-Day 841)
6. From first dose of GSK3528869A (Treatment 2-Day 1) up to study end (Treatment 2-Day 841)
7,11,14. At Days T1: 1 ,8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92,
99, 106, 113, 120, 127, 134, 141, 148, 155 and 162 (ASO24-TI & ASO24
groups) and at Days T1: 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78 (ASO12-TI & ASO12 groups)
8. At Days T2: 1, 3, 8, 15, 31, 57, 64, 71, 87, 113, 120, 127, 143, 169,
176, 183 and 199
9. At Days T2: 225, 281, 337, 421, 505, 673 and 841
10,13. At Days
T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,14
1,148,155,162; T2:1,15,31,57,71,87,113,143,169,199 (ASO24-TI&ASO24
groups); T1:1,8,15,22,29,36,43,50,57,64,71,78;
T2:1,15,31,57,71,87,113,143,169,199 (ASO12-TI&ASO12 groups)
12,15. At Days T2: 1, 15, 31, 57, 71, 87, 113, 143, 169 and 199
16,18,21. At Days T1:1,8,15,22,29,36,43,50,57,64,71,78,85,92,99,106,113,120,127,134,14
1,148,155,162 and at Days
T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
17,19,22. At Days T1:1,8,15,22,29,36,43,50,57,64,71,78 and at Days
T2:1,15,31,57,71,87,113,143,169,199,225,281,337,421,505,673,841
20. From Treatment 1-Day 1 up to first occurrence of HBsAg reversion
and/or HBV DNA reversion, assessed from Treatment 1-Day 1 up to
Treatment 2-Day 841
23,24,25,26,27,28,29. At Days T1: 1,29,57,85,113,141,162 and T2:
1,15,57,71,113,127,169,183,337,505,841 (ASO24-TI&ASO24 groups)
and at Days T1: 1,29,57 and
T2:1,15,57,71,113,127,169,183,337,505,841 (ASO12-TI&ASO12 groups)
30,31,32,33,34,35. At Days T1: 1, 78 and at Days T2: 1, 15, 71, 127, 183, 337, 505 and 841

E.5.2.1

Timepoint(s) of evaluation of this end point

Due to the character limitation, timeframes for secondary endpoints are added in section E.5.2 after endpoints.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Sequential

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Information not present in EudraCT

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

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

Philippines

Singapore

Hong Kong

Taiwan

Thailand

United Kingdom

Belgium

Bulgaria

France

Germany

Italy

Poland

Romania

Spain

Türkiye

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

End of Study (EoS): Date of the last testing/reading released of the Human Biological Samples or imaging data, related to primary and secondary endpoints. EoS must be achieved no later than 8 months after Last Subject Last Visit (LSLV).

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:

180

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

174

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)

After the participant has ended the participation in this trial they will continue with standard care.

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

2022-04-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-02-28

P. End of Trial
P.	End of Trial Status	Temporarily Halted

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Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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