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

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 to 65 years
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

43 sites in 9 countries.

About this study

Official title: A first-time-in Human (FTIH), Phase I/II, Randomized, Multi-centric, Single-blind, Controlled Dose-escalation Study to Evaluate the Reactogenicity, Safety, Immunogenicity and Efficacy of GSK Biologicals' HBV Viral Vector Vaccines Given in a Prime-boost Schedule With Sequential or Co-administration of Adjuvanted Proteins Therapeutic Vaccine (GSK3528869A) in Chronic Hepatitis B Patients (18-65 Years Old) Well Controlled Under Nucleo(s)Tide Analogue (NA) Therapy

Conditions

Hepatitis B, Chronic

Being tested

ChAd155-hIi-HBV low dose formulation, ChAd155-hIi-HBV high dose formulation, HBc-HBs/AS01B-4 low dose formulation, HBc-HBs/AS01B-4 high dose formulation, MVA-HBV low dose formulation

Medical subject headings

Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• ChAd155-hIi-HBV low dose formulationBiological

  Participants in group A1 were scheduled to receive one dose of ChAd155-hIi-HBV low dose formulation on Day 1, by intramuscular injection in the deltoid of the non-dominant arm.

• ChAd155-hIi-HBV high dose formulationBiological

  Participants in groups B1 and B3 were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation on Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the non-dominant arm.

  Participants in groups C1 and C2 were scheduled to receive one dose of ChAd155-hIi-HBV high dose formulation on Day 1 and Day 113 respectively, by intramuscular injection in the deltoid of the dominant arm.

• HBc-HBs/AS01B-4 low dose formulationBiological

  Participants in group A1 were scheduled to receive two doses of HBc-HBs/AS01B-4 low dose formulation, one on Day 113 and one on Day 169, and participants in group A2 were scheduled to receive four doses of the HBc-HBs/AS01B-4 low dose formulation, one dose each on Days 1, 57, 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.

• HBc-HBs/AS01B-4 high dose formulationBiological

  Participants in group B1 were scheduled to receive two doses of HBc-HBs/AS01B-4 high dose formulation, one on Day 113 and one on Day 169; participants in group B2 were scheduled to receive four doses of HBc-HBs/AS01B-4 high dose formulation, one dose each on Days 1, 57, 113 and 169; participants in group C1 were scheduled to receive four co-administered doses of HBc-HBs/AS01B-4 high dose formulation on Days 1, 57, 113 and 169 and participants in group C2 were scheduled to receive two co-administered doses HBc-HBs/AS01B-4 high dose formulation on Days 113 and 169, by intramuscular injection in the deltoid of the non-dominant arm.

• MVA-HBV low dose formulationBiological

  Participants in group A1 were scheduled to receive one dose of MVA-HBV low dose formulation on Day 57, by intramuscular injection in the deltoid of the non-dominant arm.

• MVA-HBV high dose formulationBiological

  Participants in groups B1 and B3 were scheduled to receive one dose of MVA-HBV high dose formulation on Day 57 and Day 169 respectively, by intramuscular injection in the deltoid of the non-dominant arm.

  Participants in group C1 were scheduled to receive three co-administered doses of the MVA-HBV high dose formulation on Days 57, 113 and 169 and participants in group C2 were scheduled to receive one co-administered dose of the MVA-HBV high dose formulation on Day 169, by intramuscular injection in the deltoid of the dominant arm.

• PlaceboDrug

  Participants in group A3 were scheduled to receive four doses of placebo, one each on Days 1, 57, 113 and 169 and participants in group B3 were scheduled to receive two doses of placebo one each on Days 1 and 57, by intramuscular injection in the deltoid of the non-dominant arm. Participants in group C2 were scheduled to receive two co-administered doses of placebo on Day 1 and two co-administered doses of placebo on Day 57, by intramuscular injection in the deltoid of the dominant and non-dominant arm.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 1

   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.

   Measured: Within 7 days after vaccination 1 occurring on Day 1

2. Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 2

   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.

   Measured: Within 7 days after vaccination 2 occurring on Day 57

3. Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 3

   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.

   Measured: Within 7 days after vaccination 3 occurring on Day 113

4. Number of Participants Reporting Any Solicited Administration Site Events After Vaccination 4

   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.

   Measured: Within 7 days after vaccination 4 occurring on Day 169

5. Number of Participants Reporting Any Solicited Systemic Events After Vaccination 1

   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.

   Measured: Within 7 days after vaccination 1 occurring on Day 1

6. Number of Participants Reporting Any Solicited Systemic Events After Vaccination 2

   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.

   Measured: Within 7 days after vaccination 2 occurring on Day 57

7. Number of Participants Reporting Any Solicited Systemic Events After Vaccination 3

   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.

   Measured: Within 7 days after vaccination 3 occurring on Day 113

8. Number of Participants Reporting Any Solicited Systemic Events After Vaccination 4

   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.

   Measured: Within 7 days after vaccination 4 occurring on Day 169

9. Number of Participants Reporting Any Unsolicited Adverse Events (AEs) After Vaccination 1

   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.

   Measured: Within 30 days after vaccination 1 occurring on Day 1

10. Number of Participants Reporting Any Unsolicited AEs After Vaccination 2

    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.

    Measured: Within 30 days after vaccination 2 occurring on Day 57

11. Number of Participants Reporting Any Unsolicited AEs After Vaccination 3

    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.

    Measured: Within 30 days after vaccination 3 occurring on Day 113

12. Number of Participants Reporting Any Unsolicited AEs After Vaccination 4

    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.

    Measured: Within 30 days after vaccination 4 occurring on Day 169

13. Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 1

    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.

    Measured: Within 30 days after vaccination 1 occurring on Day 1

14. Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 2

    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.

    Measured: Within 30 days after vaccination 2 occurring on Day 57

15. Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 3

    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.

    Measured: Within 30 days after vaccination 3 occurring on Day 113

16. Number of Participants With Hematological, Biochemical and Urinalysis Laboratory Abnormalities After Vaccination 4

    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.

    Measured: Within 30 days after vaccination 4 occurring on Day 169

17. Number of Participants Reporting Serious Adverse Events (SAEs)

    An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, or in other situations that were considered serious per medical or scientific judgment.

    Measured: From Day 1 until Day 337

18. Number of Participants Reporting Potential Immune-mediated Diseases (pIMDs)

    pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

    Measured: From Day 1 until Day 337

19. Number of Participants Reporting Liver Disease-related (LDR) Adverse Events of Special Interest (AESIs)

    LDR AESIs are defined as adverse events related to the underlying chronic HBV infection and characterized by one or more of the following:

    • ALT flares: Elevation of ALT > 3 X Upper Limit of Normal (ULN): Mild: > 3-5 X ULN, Moderate: > 5-10 X ULN, Severe: > 10 X ULN.
    • ALT flares with other substantial biochemical changes: Bilirubin >= 2 X ULN, And/or INR >1.5.
    • Hepatic decompensation: occurrence of one or more of the following events: ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, variceal bleeding, or hepatic encephalopathy.
    • HBV-Deoxyribonucleic Acid (DNA) breakthrough: any increase in serum HBV DNA by >1 log10 from nadir or redetection of serum HBV DNA at levels 10-fold the Lower Limit of Quantification (LLOQ) of the viral load after HBV DNA was undetectable.

    Measured: From Day 1 until Day 337

20. Number of Participants Reporting Hematological AESIs

    Hematological AESIs are defined as:

    • spontaneous local or general bleeding with thrombocytes <50,000 platelets/cubic millimeter (mm^3),
    • anemia with hemoglobin (Hgb) <9.5 gram/deciliter (g/dL).

    Measured: From Day 1 until Day 337

21. Number of Participants Reporting Medically-attended Adverse Events (MAEs)

    MAEs are defined as events for which the participant received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.

    Measured: From Day 1 until Day 337

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted7 Mar 2019
2. Study start28 Mar 2019
3. Primary completion7 Oct 2024
4. Study completion7 Oct 2024

Why it stopped: Following the primary phase (24 weeks post last vaccination) the predefined efficacy endpoint was not met. Noting the lack of efficacy and with the objective to prioritize participants' safety GSK has decided on the early termination of the study.

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
• More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.