Trial Outcomes & Findings for Safety, Efficacy, Immunogenicity Study of GSK Biologicals' HBV Viral Vector and Adjuvanted Proteins Vaccine (GSK3528869A) in Adult Patients With Chronic Hepatitis B Infection (NCT NCT03866187)

This study assessed safety, immunogenicity and efficacy of HBV viral vector vaccines and/or adjuvanted proteins vaccines in participants with chronic HBV infection, virally suppressed on NA therapy. Following the primary phase (ending at Day 337), the pre-defined efficacy endpoint was not met. Noting the lack of efficacy and to prioritize participants' safety, GSK decided to terminate the study. Thus, efficacy and immunogenicity analyses beyond Day 337 were not evaluated for all participants.

The changes from the planned subsequent analyses were presented as pre-specified in Statistical Analysis Plan. A total of 236 participants were enrolled in the study, out of which 102 were screening failures, and hence 134 participants received at least one dose of study intervention, were included in the Exposed Set and started the study.

Safety, Efficacy, Immunogenicity Study of GSK Biologicals' HBV Viral Vector and Adjuvanted Proteins Vaccine (GSK3528869A) in Adult Patients With Chronic Hepatitis B Infection

Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = ChAd155-hIi-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = Placebo / Vaccine B = Placebo.

Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = Placebo / Vaccine B = Placebo.

Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For step C: Group C2, Vaccine A = ChAd155-hIi-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation.

Assessed solicited administration site events included erythema, pain and swelling at the injection site. Any = occurrence of the event regardless of intensity grade. The below presented data is read as follows: * For Step C: Group C1, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation. * For Step C: Group C2, Vaccine A = MVA-HBV high dose formulation / Vaccine B = HBc-HBs-AS01B high dose formulation.

Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature greater than or equal to (\>=) 38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/ 100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

Assessed solicited systemic events included chills, fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia and fever. Fever is defined as oral temperature \>=38.0°C/100.4°F. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

An unsolicited adverse event is defined as an adverse event that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.

The assessed parameters were: * hematological: haemoglobin decrease, white blood cells (WBCs) increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin international normalized ratio (INR) increase; * biochemical: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, gamma glutamyl transferase (GGT), creatinine; * urinalysis: protein, glucose, red blood cells (RBCs). The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.

The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening. Not done = parameter value missing for the specified parameter.

The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.

The assessed parameters were: * hematological: haemoglobin decrease, WBCs increase, WBCs decrease, lymphocytes decrease, neutrophils decrease, eosinophils increase, platelets decrease, prothrombin INR increase; * biochemical: ALT, AST, ALP, total bilirubin, GGT, creatinine; * urinalysis: protein, glucose, RBCs. The grading of the parameters was derived from the standard FDA toxicity grading scale. The results are defined as follows: \<parameter\>,\<grade at baseline \[pre-vaccination (Day 1)\]\>,\<grade post-baseline\> (e.g. ALT, Grade 0, Grade 0), where Grade 0 = a non-missing parameter value for which grade could not be derived according to the grading scale and does not belong to Grade 1-4; Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life-Threatening.