Clinical Trials List
Protocol Number209668
NCT Number(ClinicalTrials.gov Identfier)NCT04449029
2020-12-02 - 2022-07-26
Phase II
Recruiting4
ICD-10B18.1
Chronic viral hepatitis B without delta-agent
ICD-9070.32
Viral hepatitis B without mention of hepatic coma, chronic, without mention of hepatitis delta
Phase llb Multi=Center, Randomised, Partial-Blind Parallel Cohort Study to Assess the Efficacy a and Safety of Treatment with GSK3228836 in Participants with Chronic Hepatitis Z Virus(B-Clear)nd Safety
-
Sponsor
GlaxoSmithKline
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃駿逸 Digestive System Department
- Chung-Feng Huang Digestive System Department
- Ming-Lung Yu Digestive System Department
- Jee-Fu Huang Digestive System Department
- Chia-Yen Dai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 邱彥程 無
- 吳毅晉 無
- Hsin-Yu Kuo 無
- 簡世杰 無
- Chiu Hung Chiu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Patients with chronic hepatitis B virus
Objectives
To assess the efficacy of three dosing regimens of GSK3228836 in
participants with chronic hepatitis B (CHB)
Primary estimands supporting the primary objective are defined as:
- Population: separate assessment for the following:
• participants with CHB on stable nucleos(t)ide therapy
• participants with CHB not currently on nucleos(t)ide therapy.
- Variable: Sustained virologic response (SVR, described in Section 9.4.2) for 24 weeks after the end of GSK3228836 treatment in the absence of rescue
medication.
- Treatments: arms 1, 2, and 3. Estimation of the within-arm response rate.
- Intercurrent events: use of rescue medication, and discontinuation
of/interruption of/adherence to IP. The use of rescue medication has been
incorporated into the definition of variable (composite strategy).
Discontinuation of, interruption of, and adherence to IP will be ignored
(treatment policy). Wide disruptive events (such as COVD19 pandemic)
preventing assessment of primary outcome will be handled assuming they had
not happened (hypothetical strategy)
- Population summary: proportion of participants who achieve SVR for each
treatment arm.
The primary estimands for each sub-population is the proportion of
participants in each treatment arm 1, 2, and 3 who achieve SVR for 24 weeks
after the end of GSK3228836 treatment in the absence of rescue medication
regardless of completing IP, interruptions in IP or adherence to IP had
they not been affected by wide disruptive events.
Test Drug
GSK3228836
Active Ingredient
GSK3228836
Dosage Form
Vial
Dosage
150mg/1mL
Endpoints
To assess the efficacy of three dosing regimens of GSK3228836 in
participants with chronic hepatitis B (CHB)
Primary estimands supporting the primary objective are defined as:
- Population: separate assessment for the following:
• participants with CHB on stable nucleos(t)ide therapy
• participants with CHB not currently on nucleos(t)ide therapy.
- Variable: Sustained virologic response (SVR, described in Section 9.4.2) for 24 weeks after the end of GSK3228836 treatment in the absence of rescue
medication.
- Treatments: arms 1, 2, and 3. Estimation of the within-arm response rate.
- Intercurrent events: use of rescue medication, and discontinuation
of/interruption of/adherence to IP. The use of rescue medication has been
incorporated into the definition of variable (composite strategy).
Discontinuation of, interruption of, and adherence to IP will be ignored
(treatment policy). Wide disruptive events (such as COVD19 pandemic)
preventing assessment of primary outcome will be handled assuming they had
not happened (hypothetical strategy)
- Population summary: proportion of participants who achieve SVR for each
treatment arm.
The primary estimands for each sub-population is the proportion of
participants in each treatment arm 1, 2, and 3 who achieve SVR for 24 weeks
after the end of GSK3228836 treatment in the absence of rescue medication
regardless of completing IP, interruptions in IP or adherence to IP had
they not been affected by wide disruptive events.
participants with chronic hepatitis B (CHB)
Primary estimands supporting the primary objective are defined as:
- Population: separate assessment for the following:
• participants with CHB on stable nucleos(t)ide therapy
• participants with CHB not currently on nucleos(t)ide therapy.
- Variable: Sustained virologic response (SVR, described in Section 9.4.2) for 24 weeks after the end of GSK3228836 treatment in the absence of rescue
medication.
- Treatments: arms 1, 2, and 3. Estimation of the within-arm response rate.
- Intercurrent events: use of rescue medication, and discontinuation
of/interruption of/adherence to IP. The use of rescue medication has been
incorporated into the definition of variable (composite strategy).
Discontinuation of, interruption of, and adherence to IP will be ignored
(treatment policy). Wide disruptive events (such as COVD19 pandemic)
preventing assessment of primary outcome will be handled assuming they had
not happened (hypothetical strategy)
- Population summary: proportion of participants who achieve SVR for each
treatment arm.
The primary estimands for each sub-population is the proportion of
participants in each treatment arm 1, 2, and 3 who achieve SVR for 24 weeks
after the end of GSK3228836 treatment in the absence of rescue medication
regardless of completing IP, interruptions in IP or adherence to IP had
they not been affected by wide disruptive events.
Inclution Criteria
1. At least 18 years of age at the time of signing the informed consent. (The subject
in this study in Taiwan must be at or over 20 years of age.)
2. Participants who have documented chronic HBV infection ≥6 months prior to screening AND
a. Not currently on nucleos(t)ide analogue therapy population defined as
participants who never received HBV treatment (treatment naïve) OR must have
ended nucleos(t)ide therapy at least 6 months prior to the screening visit
b. OR Currently receiving stable nucleos(t)ide analogue therapy population
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
3. Plasma or serum HBsAg concentration >100 IU/mL
4. Plasma or serum HBV DNA concentration
a. Participants not currently on nucleos(t)ide analogue therapy, plasma or serum
HBV DNA >2000 IU/mL
b. Participants who are receiving stable nucleos(t)ide analogue therapy must
be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL
5. Alanine Transaminase (ALT)
a. ALT for treatment naïve participants and for participants who are not
currently receiving treatment
i. ALT <3 X ULN will be included initially
1) If agreed by the IDMC after review of safety data, the ALT inclusion
criteria may be expanded to include participants with ALT <5 X ULN
b. ALT ≤2 X ULN for participants who are receiving stable nucleos(t)ide analogue
therapy
6. Male and/or Female
a. A male participant is eligible to participate if they agree to the following
during the intervention period and for at least 90 days after the last dose
of study treatment
i. Refrain from donating sperm
ii. 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
1) 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 who is not currently pregnant.
b. A female participant is eligible to participate:
i. If she is not pregnant or breastfeeding
ii. AND at least one of the following conditions applies:
1) Is not a woman of childbearing potential (WOCBP)
2) OR 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
iii. A WOCBP must have both
1) A confirmed menstrual period prior to the first dose of study
intervention [additional evaluation (e.g., amenorrhea in athletes,
birth control) should also be considered]
2) AND a negative highly sensitive pregnancy test [urine or serum] within
24 hours before the first dose of study treatment
7. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this protocol.
in this study in Taiwan must be at or over 20 years of age.)
2. Participants who have documented chronic HBV infection ≥6 months prior to screening AND
a. Not currently on nucleos(t)ide analogue therapy population defined as
participants who never received HBV treatment (treatment naïve) OR must have
ended nucleos(t)ide therapy at least 6 months prior to the screening visit
b. OR Currently receiving stable nucleos(t)ide analogue therapy population
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
3. Plasma or serum HBsAg concentration >100 IU/mL
4. Plasma or serum HBV DNA concentration
a. Participants not currently on nucleos(t)ide analogue therapy, plasma or serum
HBV DNA >2000 IU/mL
b. Participants who are receiving stable nucleos(t)ide analogue therapy must
be adequately suppressed, defined as plasma or serum HBV DNA <90 IU/mL
5. Alanine Transaminase (ALT)
a. ALT for treatment naïve participants and for participants who are not
currently receiving treatment
i. ALT <3 X ULN will be included initially
1) If agreed by the IDMC after review of safety data, the ALT inclusion
criteria may be expanded to include participants with ALT <5 X ULN
b. ALT ≤2 X ULN for participants who are receiving stable nucleos(t)ide analogue
therapy
6. Male and/or Female
a. A male participant is eligible to participate if they agree to the following
during the intervention period and for at least 90 days after the last dose
of study treatment
i. Refrain from donating sperm
ii. 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
1) 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 who is not currently pregnant.
b. A female participant is eligible to participate:
i. If she is not pregnant or breastfeeding
ii. AND at least one of the following conditions applies:
1) Is not a woman of childbearing potential (WOCBP)
2) OR 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
iii. A WOCBP must have both
1) A confirmed menstrual period prior to the first dose of study
intervention [additional evaluation (e.g., amenorrhea in athletes,
birth control) should also be considered]
2) AND a negative highly sensitive pregnancy test [urine or serum] within
24 hours before the first dose of study treatment
7. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this protocol.
Exclusion Criteria
1. Clinically significant abnormalities, aside from chronic HBV infection in
medical history (e.g., moderate-severe liver disease other than chronic HBV,
acute coronary syndrome within 6 months of screening, major surgery within 3
months of screening, significant/unstable cardiac disease, uncontrolled
diabetes, bleeding diathesis or coagulopathy) or physical examination.
2. Co-infection with:
a. Current or past history of Hepatitis C virus (HCV)
b. Human immunodeficiency virus (HIV)
c. Hepatitis D virus (HDV)
3. History of or suspected liver cirrhosis and/or evidence of cirrhosis as
determined by
a. both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and
FibroSure/FibroTest result >0.7
i.If only one parameter (APRI or FibroSure/FibroTest) result is positive,
a discussion with the Medical Monitor is required before inclusion in
study is permitted
b. Regardless of APRI of Fibrosure/FibroTest score, if the participant meets
one of the following criteria, they will be excluded from the study
i.Liver biopsy (i.e., Metavir Score F4)
ii. Liver stiffness >12 kPa
4. Diagnosed or suspected hepatocellular carcinoma as evidenced by the following
a. Alpha-fetoprotein concentration ≥200 ng/mL
b. If the screening alpha fetoprotein concentration is ≥50 ng/mL and <200 ng/mL,
the absence of liver mass must be documented by imaging within 6 months before
randomization
5. History of malignancy within the past 5 years with the exception of specific
cancers that are cured by surgical resection (e.g., skin cancer). Participants
under evaluation for possible malignancy are not eligible.
6. History of vasculitis or presence of symptoms and signs of potential vasculitis
[e.g., vasculitic rash, skin ulceration, repeated blood detected in urine
without identified cause] or history/presence of other diseases that may be
associated with vasculitis condition (e.g., systemic lupus erythematosus,
rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex)
7. History of extrahepatic disorders possibly related to HBV immune conditions
(e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis
nodosa, cryoglobulinaemia, uncontrolled hypertension)
8. ANCA at screening by itself won’t be an exclusion criterion, but if results are borderline positive or positive:
a. MPO-ANCA [pANCA] and PR3-ANCA [cANCA] analysis will be conducted
b. A discussion with the Medical Monitor will be required to review
participant’s complete medical history to ensure no past history or current
manifestations of a vasculitic/inflammatory/auto-immune condition before
inclusion in study is permitted
9. Low C3 at screening by itself won’t be an exclusion criterion, but if it is
present
a. A discussion with the Medical Monitor is required to review participant’s
complete medical history to ensure no past history or current manifestations
of vasculitic/inflammatory/auto-immune conditions
10. History of alcohol or drug abuse/dependence
a. Current alcohol use as judged by investigator to potentially interfere with
participant compliance
b. History of or current drug abuse/dependence as judged by the investigator
to potentially interfere with participant compliance
i. Refers to illicit drugs and substances with abuse potential.
Medications that are used by the participant as directed, whether
over-the-counter or through prescription, are acceptable and would not
meet the exclusion criteria
11. Currently taking, or took within 3 months of screening, any immunosuppressing
drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or
topical/inhaled steroid use.
12. Participants for whom immunosuppressive treatment is not advised, including
therapeutic doses of steroids, will be excluded
13. Currently taking, or took within 12 months of screening, any interferon-containing therapy.
14. Participants requiring anti-coagulation therapies (for example warfarin,
Factor Xa inhibitors or anti-platelet agents like clopidogrel)
15. The participant has participated in a clinical trial and has received an
investigational product within the following time period prior to the first
dosing day in the current study: 5 half-lives (if known) or twice the duration
(if known) of the biological effect of the study treatment (whichever is longer)
or 90 days (if half-life or duration is unknown).
16. Prior treatment with any oligonucleotide or small interfering RNA (siRNA)
within 12 months prior to the first dosing day
17. Fridericia’s QT correction formula (QTcF) ≥450 msec (if single
electrocardiogram [ECG] at screening shows QTcF ≥450 msec, a mean of triplicate
measurements should be used to confirm that participant meets exclusion
criterion).
18. Laboratory results as follows
a. Serum albumin <3.5 g/dL
b. Glomerular filtration rate (GFR) <60 mL/min /1.73m2
as calculated by the
CKD-EPI formula (for Japan, JSN-CKDI equation).
c. INR >1.25
d. Platelet count <140 X 109
/L
e. Total bilirubin >1.25 x ULN
i. For participants with benign unconjugated hyperbilirubinemia with
total bilirubin >1.25 x ULN, discussion for inclusion to the study is
required with the Medical Monitor
f. Urine albumin to creatinine ratio (ACR) ≥0.03 mg/mg (or ≥30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second
measurement
i. In cases where participants have low urine albumin and low urine
creatinine levels resulting in a urine ACR calculation ≥0.03 mg/mg (or
≥30 mg/g), the investigator should confirm that the participant does
not have a history of diabetes, hypertension or other risk factors that
may affect renal function and discuss with the Medical Monitor, or
designee
19. History of/sensitivity to GSK3228836 or components thereof or a history of drug
or other allergy that, in the opinion of the investigator or Medical Monitor,
contraindicates their participation
medical history (e.g., moderate-severe liver disease other than chronic HBV,
acute coronary syndrome within 6 months of screening, major surgery within 3
months of screening, significant/unstable cardiac disease, uncontrolled
diabetes, bleeding diathesis or coagulopathy) or physical examination.
2. Co-infection with:
a. Current or past history of Hepatitis C virus (HCV)
b. Human immunodeficiency virus (HIV)
c. Hepatitis D virus (HDV)
3. History of or suspected liver cirrhosis and/or evidence of cirrhosis as
determined by
a. both Aspartate aminotransferase (AST)-Platelet Index (APRI) >2 and
FibroSure/FibroTest result >0.7
i.If only one parameter (APRI or FibroSure/FibroTest) result is positive,
a discussion with the Medical Monitor is required before inclusion in
study is permitted
b. Regardless of APRI of Fibrosure/FibroTest score, if the participant meets
one of the following criteria, they will be excluded from the study
i.Liver biopsy (i.e., Metavir Score F4)
ii. Liver stiffness >12 kPa
4. Diagnosed or suspected hepatocellular carcinoma as evidenced by the following
a. Alpha-fetoprotein concentration ≥200 ng/mL
b. If the screening alpha fetoprotein concentration is ≥50 ng/mL and <200 ng/mL,
the absence of liver mass must be documented by imaging within 6 months before
randomization
5. History of malignancy within the past 5 years with the exception of specific
cancers that are cured by surgical resection (e.g., skin cancer). Participants
under evaluation for possible malignancy are not eligible.
6. History of vasculitis or presence of symptoms and signs of potential vasculitis
[e.g., vasculitic rash, skin ulceration, repeated blood detected in urine
without identified cause] or history/presence of other diseases that may be
associated with vasculitis condition (e.g., systemic lupus erythematosus,
rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex)
7. History of extrahepatic disorders possibly related to HBV immune conditions
(e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis
nodosa, cryoglobulinaemia, uncontrolled hypertension)
8. ANCA at screening by itself won’t be an exclusion criterion, but if results are borderline positive or positive:
a. MPO-ANCA [pANCA] and PR3-ANCA [cANCA] analysis will be conducted
b. A discussion with the Medical Monitor will be required to review
participant’s complete medical history to ensure no past history or current
manifestations of a vasculitic/inflammatory/auto-immune condition before
inclusion in study is permitted
9. Low C3 at screening by itself won’t be an exclusion criterion, but if it is
present
a. A discussion with the Medical Monitor is required to review participant’s
complete medical history to ensure no past history or current manifestations
of vasculitic/inflammatory/auto-immune conditions
10. History of alcohol or drug abuse/dependence
a. Current alcohol use as judged by investigator to potentially interfere with
participant compliance
b. History of or current drug abuse/dependence as judged by the investigator
to potentially interfere with participant compliance
i. Refers to illicit drugs and substances with abuse potential.
Medications that are used by the participant as directed, whether
over-the-counter or through prescription, are acceptable and would not
meet the exclusion criteria
11. Currently taking, or took within 3 months of screening, any immunosuppressing
drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or
topical/inhaled steroid use.
12. Participants for whom immunosuppressive treatment is not advised, including
therapeutic doses of steroids, will be excluded
13. Currently taking, or took within 12 months of screening, any interferon-containing therapy.
14. Participants requiring anti-coagulation therapies (for example warfarin,
Factor Xa inhibitors or anti-platelet agents like clopidogrel)
15. The participant has participated in a clinical trial and has received an
investigational product within the following time period prior to the first
dosing day in the current study: 5 half-lives (if known) or twice the duration
(if known) of the biological effect of the study treatment (whichever is longer)
or 90 days (if half-life or duration is unknown).
16. Prior treatment with any oligonucleotide or small interfering RNA (siRNA)
within 12 months prior to the first dosing day
17. Fridericia’s QT correction formula (QTcF) ≥450 msec (if single
electrocardiogram [ECG] at screening shows QTcF ≥450 msec, a mean of triplicate
measurements should be used to confirm that participant meets exclusion
criterion).
18. Laboratory results as follows
a. Serum albumin <3.5 g/dL
b. Glomerular filtration rate (GFR) <60 mL/min /1.73m2
as calculated by the
CKD-EPI formula (for Japan, JSN-CKDI equation).
c. INR >1.25
d. Platelet count <140 X 109
/L
e. Total bilirubin >1.25 x ULN
i. For participants with benign unconjugated hyperbilirubinemia with
total bilirubin >1.25 x ULN, discussion for inclusion to the study is
required with the Medical Monitor
f. Urine albumin to creatinine ratio (ACR) ≥0.03 mg/mg (or ≥30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second
measurement
i. In cases where participants have low urine albumin and low urine
creatinine levels resulting in a urine ACR calculation ≥0.03 mg/mg (or
≥30 mg/g), the investigator should confirm that the participant does
not have a history of diabetes, hypertension or other risk factors that
may affect renal function and discuss with the Medical Monitor, or
designee
19. History of/sensitivity to GSK3228836 or components thereof or a history of drug
or other allergy that, in the opinion of the investigator or Medical Monitor,
contraindicates their participation
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
440 participants
