Safety, Efficacy, Immunogenicity Study of GSK Biologicals' HBV Viral Vector and Adjuvanted Proteins Vaccine (GSK3528869A) in Adult Patients With Chronic Hepatitis B Infection
NCT ID: NCT03866187
Last Updated: 2024-11-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1/PHASE2
135 participants
INTERVENTIONAL
2019-03-28
2024-10-07
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
* Step A (low dose of each vaccine): Approximately 15 patients will be randomized (1:1:1). Fourteen days after the 2nd vaccination, iSRC will review all available safety data (of at least 12 patients if approved by local authorities). If considered appropriate to continue, Step B will start.
* Step B (prime-boost with ChAd155-hIi-HBV and Modified Vaccinia Ankara HBV vaccine (MVA-HBV) and sequential administration with HBc-HBs/AS01B-4): Approximately 40 patients will first be randomized (2:1:1) for vaccination. Fourteen days after the 2nd vaccination, iSRC will review all available safety data. If considered appropriate to continue, approximately 36 additional patients will be randomized for vaccination.
* Step C (prime-boost with ChAd155-hIi-HBV and MVA-HBV and co-administration with HBc-HBs/AS01B-4): Step C randomization (2:1) will start post completion of Step B enrolment.
TREATMENT
SINGLE
Study Groups
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Group A1_Step A
Subjects aged 18-65 years receive one dose of each of the study vaccines, Chimpanzee adenovirus HBV vaccine (ChAd155-hIi-HBV) low dose formulation at Day 1, Modified Vaccinia Ankara HBV vaccine (MVA-HBV) low dose formulation at Day 57 and two doses of HBc-HBs/AS01B-4 low dose formulation, one at Day 113 and one at Day 169.
ChAd155-hIi-HBV low dose formulation
Subjects in group A1 receive one dose of ChAd155-hIi-HBV low dose formulation at Day 1, by intramuscular injection in the deltoid of the non-dominant arm.
HBc-HBs/AS01B-4 low dose formulation
Subjects in group A1 receive two doses of HBc-HBs/AS01B-4 low dose formulation, one at Day 113 and one at Day 169 and subjects in group A2 receive four doses of the low dose formulation, one dose each at Days 1, 57, 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV low dose formulation
Subjects in group A1 receive one dose of MVA-HBV low dose formulation at Day 57, by intramuscular injection in the deltoid of the non-dominant arm.
Group A2_Step A
Subjects aged 18-65 years receive four doses of the study vaccine HBc-HBs/AS01B-4 low dose formulation, one dose each at Days 1, 57, 113 and 169.
HBc-HBs/AS01B-4 low dose formulation
Subjects in group A1 receive two doses of HBc-HBs/AS01B-4 low dose formulation, one at Day 113 and one at Day 169 and subjects in group A2 receive four doses of the low dose formulation, one dose each at Days 1, 57, 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
Group A3_Step A
Subjects aged 18-65 years receive four doses of placebo, one dose each at Days 1, 57, 113 and 169.
Placebo
Subjects in group A3 receive four doses of placebo, one each at Days 1, 57, 113 and 169 and subjects in group B3 receive two doses of placebo one each at Days 1 and 57, by intramuscular injection in the deltoid of the non-dominant arm. Subjects in group C2 receive 2 co-administered doses of placebo at Days 1 and 57, by intramuscular injection in the deltoid of the dominant and non-dominant arm.
Group B1_Step B
Subjects aged 18-65 years receive one dose of each of the study vaccines, ChAd155-hIi-HBV high dose formulation at Day 1, MVA-HBV high dose formulation at Day 57 and two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at Day 169.
ChAd155-hIi-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in groups C1 and C2 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.
HBc-HBs/AS01B-4 high dose formulation
Subjects in group B1 receive two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at 169; subjects in group B2 receive four doses, one dose each at Days 1, 57, 113 and 169; subjects in group C1 receive four co-administered doses at Days 1, 57, 113 and 169 and subjects in group C2 receive two co-administered doses at Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of MVA-HBV high dose formulation at Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in group C1 receive three co-administered doses of the vaccine at Days 57, 113 and 169 and subjects in group C2 receive one co-administered dose of the vaccine at Day 169, by intramuscular injection in the deltoid of the dominant arm.
Group B2_Step B
Subjects aged 18-65 years receive four doses of the study vaccine HBc-HBs/AS01B-4 high dose formulation, one dose each at Days 1, 57, 113 and 169.
HBc-HBs/AS01B-4 high dose formulation
Subjects in group B1 receive two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at 169; subjects in group B2 receive four doses, one dose each at Days 1, 57, 113 and 169; subjects in group C1 receive four co-administered doses at Days 1, 57, 113 and 169 and subjects in group C2 receive two co-administered doses at Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
Group B3_Step B
Subjects aged 18-65 years receive two doses of placebo, one each at Days 1 and 57, one dose of ChAd155-hIi-HBV high dose formulation at Day 113 and one dose of MVA-HBV high dose formulation at Day 169.
ChAd155-hIi-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in groups C1 and C2 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.
MVA-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of MVA-HBV high dose formulation at Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in group C1 receive three co-administered doses of the vaccine at Days 57, 113 and 169 and subjects in group C2 receive one co-administered dose of the vaccine at Day 169, by intramuscular injection in the deltoid of the dominant arm.
Placebo
Subjects in group A3 receive four doses of placebo, one each at Days 1, 57, 113 and 169 and subjects in group B3 receive two doses of placebo one each at Days 1 and 57, by intramuscular injection in the deltoid of the non-dominant arm. Subjects in group C2 receive 2 co-administered doses of placebo at Days 1 and 57, by intramuscular injection in the deltoid of the dominant and non-dominant arm.
Group C1_Step C
Subjects aged 18-65 years receive one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation at Day 1 and the 3 following doses of MVA-HBV high dose formulation co-administered with HBc-HBc-HBs/AS01B-4 high dose formulation at Day 57, 113 and Day 169.
ChAd155-hIi-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in groups C1 and C2 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.
HBc-HBs/AS01B-4 high dose formulation
Subjects in group B1 receive two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at 169; subjects in group B2 receive four doses, one dose each at Days 1, 57, 113 and 169; subjects in group C1 receive four co-administered doses at Days 1, 57, 113 and 169 and subjects in group C2 receive two co-administered doses at Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of MVA-HBV high dose formulation at Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in group C1 receive three co-administered doses of the vaccine at Days 57, 113 and 169 and subjects in group C2 receive one co-administered dose of the vaccine at Day 169, by intramuscular injection in the deltoid of the dominant arm.
Group C2_Step C
Subjects aged 18-65 years receive two doses of placebo at Days 1 and 57, one dose of ChAd155-hIi-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation at Day 113 and one dose of MVA-HBV high dose formulation co-administered with HBc-HBs/AS01B-4 high dose formulation at Day 169.
ChAd155-hIi-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in groups C1 and C2 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.
HBc-HBs/AS01B-4 high dose formulation
Subjects in group B1 receive two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at 169; subjects in group B2 receive four doses, one dose each at Days 1, 57, 113 and 169; subjects in group C1 receive four co-administered doses at Days 1, 57, 113 and 169 and subjects in group C2 receive two co-administered doses at Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of MVA-HBV high dose formulation at Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in group C1 receive three co-administered doses of the vaccine at Days 57, 113 and 169 and subjects in group C2 receive one co-administered dose of the vaccine at Day 169, by intramuscular injection in the deltoid of the dominant arm.
Placebo
Subjects in group A3 receive four doses of placebo, one each at Days 1, 57, 113 and 169 and subjects in group B3 receive two doses of placebo one each at Days 1 and 57, by intramuscular injection in the deltoid of the non-dominant arm. Subjects in group C2 receive 2 co-administered doses of placebo at Days 1 and 57, by intramuscular injection in the deltoid of the dominant and non-dominant arm.
Interventions
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ChAd155-hIi-HBV low dose formulation
Subjects in group A1 receive one dose of ChAd155-hIi-HBV low dose formulation at Day 1, by intramuscular injection in the deltoid of the non-dominant arm.
ChAd155-hIi-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in groups C1 and C2 receive one dose of ChAd155-hIi-HBV high dose formulation at Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.
HBc-HBs/AS01B-4 low dose formulation
Subjects in group A1 receive two doses of HBc-HBs/AS01B-4 low dose formulation, one at Day 113 and one at Day 169 and subjects in group A2 receive four doses of the low dose formulation, one dose each at Days 1, 57, 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
HBc-HBs/AS01B-4 high dose formulation
Subjects in group B1 receive two doses of HBc-HBs/AS01B-4 high dose formulation, one at Day 113 and one at 169; subjects in group B2 receive four doses, one dose each at Days 1, 57, 113 and 169; subjects in group C1 receive four co-administered doses at Days 1, 57, 113 and 169 and subjects in group C2 receive two co-administered doses at Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV low dose formulation
Subjects in group A1 receive one dose of MVA-HBV low dose formulation at Day 57, by intramuscular injection in the deltoid of the non-dominant arm.
MVA-HBV high dose formulation
Subjects in groups B1 and B3 receive one dose of MVA-HBV high dose formulation at Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.
Subjects in group C1 receive three co-administered doses of the vaccine at Days 57, 113 and 169 and subjects in group C2 receive one co-administered dose of the vaccine at Day 169, by intramuscular injection in the deltoid of the dominant arm.
Placebo
Subjects in group A3 receive four doses of placebo, one each at Days 1, 57, 113 and 169 and subjects in group B3 receive two doses of placebo one each at Days 1 and 57, by intramuscular injection in the deltoid of the non-dominant arm. Subjects in group C2 receive 2 co-administered doses of placebo at Days 1 and 57, by intramuscular injection in the deltoid of the dominant and non-dominant arm.
Eligibility Criteria
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Inclusion Criteria
* Written informed consent obtained from the patient prior to performing any study specific procedure.
* A male or female between, and including, 18 and 65 years of age at the time of the first vaccination.
* Female patients of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as hysterectomy, bilateral ovariectomy or post-menopause.
* Female patients of childbearing potential may be enrolled in the study if the patient:
* has practiced adequate contraception for 30 days prior to vaccination, and
* has a negative pregnancy test at Screening, and
* has agreed to continue adequate contraception from Screening until 12 weeks after completion of the vaccination series
* Male patients:
* with documented bilateral vasectomy and resultant azoospermia, bilateral orchiectomy or azoospermia, or
* who agree to practice abstinence from penile-vaginal intercourse (when this is their preferred and usual lifestyle) or use condoms from Screening until 12 weeks after completion of the vaccination series.
* Chronic Hepatitis B (CHB) patient, under and adherent to treatment with a nucleo(s)tide analogue with high barrier to resistance given as per approved label/dosage for at least 24 months.
* Documented medical history of Hepatitis B Virus e Antigen (HBeAg)-negative CHB prior to onset of NA therapy (applicable to all patients in Step A and Step B and to some patients in Step C) or documented medical history of HBeAg-negative CHB over a period of at least 24 months prior screening (applicable to some patients in Step C only).
* Documented HBV viral suppression as per local clinical diagnosis within the previous 24 months AND at Screening test HBV DNA \< 10 IU/mL. If no results are available, two Screening tests need to be performed at least 2 weeks apart. Small fluctuations of HBV DNA (≤ 10 x LLOQ; LLOQ defined by laboratory that performed testing) are allowed provided HBV DNA is \< 10 IU/mL at Screening and was clearly not rising during the previous 24 months.
* Documented normal level of ALT as per local clinical diagnosis within the previous 24 months AND at Screening test ALT \< 48U/L. Small fluctuations of ALT (≤ 1.5 X ULN) are allowed provided ALT\< 48 U/L at Screening. If no results are available, two Screening tests need to be performed at least 2 weeks apart. ULN are to be defined according to local laboratory reference range.
* No clinical diagnosis of cirrhosis (e.g. F4 by METAVIR scoring system or ≥ 6 by Ishak scoring system or FibroScan TE score \> 12.5 kPa) within the previous 24 months.
* FibroScan Transient Elastography (TE) score \< 9.6 kPa and FibroTest score \< 0.59 at Screening. A patient with one of these parameters out of range, but having the liver biopsy within 12 months before screening that showed F0-2 by METAVIR scoring system or stage 0-4 by Ishak scoring system, can be included.
* HBsAg concentration \> 50 IU/mL and anti-HBs negative at Screening.
* Anti-HBc positive at Screening.
* HBeAg-negative at Screening.
Exclusion Criteria
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 10 mg/day or equivalent. Inhaled and topical steroids are allowed.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period.
* Use of systemic cytotoxic agents, chronic antiviral agents or Chinese herbal medicines which, in the opinion of the investigator, may have activity against HBV within the previous 6 months prior to randomization into this study. Antiviral treatment/prevention for influenza or herpes simplex virus is allowed.
* Administration of adenovirus/adenovector-based or MVA-based vaccine within the last 12 months 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 months (applicable for the patients in France only).
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 14 days before each dose and ending 30 days after each dose of vaccines, with the exception of influenza vaccine that may be given at any time except within a 7-day period before or after each vaccine 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. Note: If the type of COVID-19 vaccine is unknown, the allowed interval of 30 days before or after each study vaccine dose should be followed.
* Treatment with nephrotoxic drugs or competitors of renal excretion within 2 months prior to Screening or the expectation that patient will receive any of these during the course of the study. TAF/TDF given as NA therapy is allowed.
* Concurrently participating in another clinical study, at any time during the study period, in which the patient has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Medical history of cirrhosis or hepatic decompensation.
* Planned for liver transplantation or previous liver transplantation.
* Personal or family (first degree) history of autoimmune disease.
* Family history of congenital or hereditary immunodeficiency.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* Evidence of Hepatitis C Virus and hepatitis D Virus infection.
* Suspicion of or confirmed Hepatocellular Carcinoma or any other liver cancer in medical history or at Screening:
* Suspicious foci at liver imaging exam
* Elevated α-fetoprotein \> 50 ng/mL.
* Documented evidence of other currently active cause of hepatitis.
* Hematology and biochemistry parameters outside normal clinical range at Screening:
Biochemistry:
* Glomerular filtration rate \< 60 mL/min
* Bilirubin \> 27.5 µmol/L unless \*or the diagnosis of Gilbert Syndrome has been established and confirmed by the Investigator
* GGT \> 65 U/L (males) or \> 45 U/L (females)\*
* ALT \> 48 U/L
* AST \> 42 U/L\*
* ALP \> 125 U/L\*
Hematology:
* Hemoglobin \< 12.0 g/dL (females) or \< 13.5 g/dL (males)\*
* Red blood cell count \< 3.9 x 10\^6 cells/mm\^3 (females) or \< 4.4 x 10\^6 cells/mm\^3 (males)\*
* White blood cell count \< 3,500 cells/mm\^3 or \> 12,000 cells/mm\^3\*
* Platelets \< 140,000 cells/mm\^3
* INR \> 1.32 (i.e. 1.1 x ULN) \*unless it is considered as clinically not significant by the Investigator
* Known diabetes Type I.
* Body Mass Index \> 35 kg/m\^2 at Screening.
* Any serious or active medical or psychiatric illnesses other than chronic hepatitis B which, in the opinion of the investigator, would interfere with patient treatment, assessment or compliance with the protocol.
* History of or current drug abuse and/or excess of alcohol consumption as defined per local guidelines.
* HIV-positive patient.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions in the period starting from the Screening Visit up to 12 weeks post-last vaccination visit.
* Fever and or acute minor illness may be enrolled for Screening at the discretion of the investigator, provided that the condition is resolved at the time of vaccination.
18 Years
65 Years
ALL
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Responsible Party
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Principal Investigators
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GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
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GSK Investigational Site
Antwerp, , Belgium
GSK Investigational Site
Brussels, , Belgium
GSK Investigational Site
Edegem, , Belgium
GSK Investigational Site
Ghent, , Belgium
GSK Investigational Site
Clichy, , France
GSK Investigational Site
Créteil, , France
GSK Investigational Site
Lyon, , France
GSK Investigational Site
Strasbourg, , France
GSK Investigational Site
Aachen, , Germany
GSK Investigational Site
Berlin, , Germany
GSK Investigational Site
Bonn, , Germany
GSK Investigational Site
Essen, , Germany
GSK Investigational Site
Frankfurt, , Germany
GSK Investigational Site
Hamburg, , Germany
GSK Investigational Site
Mainz, , Germany
GSK Investigational Site
Tübingen, , Germany
GSK Investigational Site
Pokfulam, , Hong Kong
GSK Investigational Site
Krakow, , Poland
GSK Investigational Site
Mysłowice, , Poland
GSK Investigational Site
Poznan, , Poland
GSK Investigational Site
Łańcut, , Poland
GSK Investigational Site
Barcelona, , Spain
GSK Investigational Site
Barcelona, , Spain
GSK Investigational Site
Córdoba, , Spain
GSK Investigational Site
Granada, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Madrid, , Spain
GSK Investigational Site
Palma de Mallorca, , Spain
GSK Investigational Site
Santander, , Spain
GSK Investigational Site
Seville, , Spain
GSK Investigational Site
TorrejOn Ardoz Madrid, , Spain
GSK Investigational Site
Taichung, , Taiwan
GSK Investigational Site
Taichung, , Taiwan
GSK Investigational Site
Tainan City, , Taiwan
GSK Investigational Site
Taipei, , Taiwan
GSK Investigational Site
Taoyuan District, , Taiwan
GSK Investigational Site
Bangkok, , Thailand
GSK Investigational Site
Chiang Mai, , Thailand
GSK Investigational Site
London, , United Kingdom
GSK Investigational Site
London, , United Kingdom
GSK Investigational Site
Nottingham, , United Kingdom
Countries
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Other Identifiers
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2017-001452-55
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
204852
Identifier Type: -
Identifier Source: org_study_id