Chronic hepatitis B MedDRA version: 20.1 Level: PT Classification code 10008910 Term: Chronic hepatitis B System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: TH HBV adjuvanted recombinant proteins vaccine (80-80) High dose formulation
Product Code: HBc-HBs/AS01B-4 80-80 vaccine component
Pharmaceutical Form: Powder and suspension for suspensi
Sponsors
GlaxoSmithKline Biologicals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients who, in the opinion of the investigator, can and will comply with the requirements of the protocol •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 12.5kPa) within the previous 24 months •FibroScan Transient Elastography (TE) score 50 IU/mL and anti-HBs negative at Screening •Anti-HBc positive at Screening •HBeAg-negative at Screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 74 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 74
Exclusion criteria
Exclusion criteria: •Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines or planned use during the study period •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. •Medical history of cirrhosis •Medical history of 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 a-fetoprotein > 50 ng/mL •Documented evidence of other currently active cause of hepatitis •Hematology and biochemistry parameters outside normal clinical range at Screenin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of escalating doses of the HBV viral vector vaccines (prime-boost) and/or adjuvanted proteins vaccines in patients with chronic HBV infection who are virally suppressed on NA therapy;Secondary Objective: To assess in patients with chronic HBV infection who are virally suppressed on NA therapy: •immunogenicity •efficacy of the HBV viral vector vaccines (prime-boost) and/or adjuvanted proteins vaccines and •the long-term safety of escalating doses of the HBV viral vector vaccines (prime-boost) and/or adjuvanted proteins vaccines Proof-of-principle (PoP) for the efficacy objective will be achieved if 1)At least 15% of patients (i.e. lower limit of 80% CI of at least 15%) in 1 vaccine group show at least 10-fold decrease (i.e. 1-log difference) in Quantitative Hepatitis B Surface Antigen (qHBsAg) or show HBsAg loss at Day 337 versus Day 1, or 2)If there is at least 10-fold difference in mean HBsAg concentration between a vaccine group at Day 337 and the respective control group (i.e. the criterion is to observe a point estimate of at least 10-fold decrease between the groups with statistical significance, i.e., 80% CI on the ratio not including 1);Primary end point(s): 1. Number of subjects reporting solicited local adverse events (AEs) 2. Number of subjects reporting solicited general AEs 3. Number of subjects reporting unsolicited AEs 4. Number of subjects with hematological, biochemical or urinalysis laboratory abnormalities 5. Number of subjects reporting serious adverse events (SAEs) 6. Number of subjects reporting potential immune-mediated diseases (pIMDs) 7. Number of subjects reporting liver-disease-related (LDR) AEs 8. Number of subjects reporting any hematological adverse events of specific interest (AESIs) 9. Number of subjects reporting medically-attended adverse events (MAEs);Timepoint(s) of evaluation of this end point: 1. Within 7 days after each vaccination (from day of vaccination to 6 days after vaccinati | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of seropositive subjects for anti-hepatitis B core antibody (anti-HBc) 2. Evaluation of immunogenicity in terms of Anti-HBc antibody concentration 3. Number of subjects with anti-hepatitis B surface antigen (anti-HBs) seroconversion 4. Evaluation of immunogenicity in terms of anti-HBs antibody concentration 5. Number of subjects with anti-HBs antibody concentration equal to or above 10 mIU/mL 6. Number of subjects with anti-HBs antibody concentration equal to or above 100 mIU/mL 7. Frequency of HBs-specific CD4+ T-cells 8. Frequency of HBs-specific CD8+ T-cells 9. Frequency of HBc-specific CD4+ T-cells 10. Frequency of HBc-specific CD8+ T-cells 11. Frequency of HBs- specific CD4+ T-cells responders 12. Frequency of HBc- specific CD4+ T-cells responders 13. Frequency of HBs- specific CD8+ T-cells responders 14. Frequency of HBc- specific CD8+ T-cells responders 15. Number of subjects with = 0.5 log decrease of qHBsAg since pre-vaccination 16. Number of subjects with = 1 log decrease of qHBsAg since pre-vaccination 17. Number of subjects with qHBsAg loss 18. Changes in qHBsAg since pre-vaccination 19. Number of subjects with HBsAg loss and anti-HBs seroconversion 20. Evaluation of qHBsAg geometric mean concentrations 21. Number of subjects reporting any SAEs and SAEs causally related to an investigational vaccine 22. Number of subjects reporting MAEs 23. Number of subjects reporting pIMDs 24. Number of subjects reporting liver-disease-related AEs 25. Number of subjects reporting spontaneous local or general bleeding with thrombocytopenia 26. Number of subjects reporting anemia 27. Number of subjects reporting AEs and SAEs leading to study withdrawal 28. Number of subjects reporting pregnancy and outcomes of reported pregnancy ;Timepoint(s) of evaluation of this end point: Endpoint(s) 1, 2, 3, 4, 5 and 6: At Days 1, 15, 71, 113, 127, 183, 337, 505 and 841 Endpoints 7, 8, 9, 10, 11, 12, 13 and 14: At Days 1, 15, 57, | — |
Countries
Belgium, France, Germany, Hong Kong, Poland, Spain, Taiwan, Thailand, United Kingdom
Contacts
Public ContactClinical Disclosure Advisor
GlaxoSmithKline Biologicals
Outcome results
None listed