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Hepatitis BPhase 2NCT03020745

A Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3389404 in Chronic Hepatitis B (CHB) Subjects

A Phase 2 study testing GSK3389404 in people with Hepatitis B, run by GlaxoSmithKline at 21 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

GSK3389404 is being developed for the treatment of CHB virus infection. The development goal for GSK3389404 is the establishment of a finite duration treatment that results in sustained suppression of hepatitis B virus (HBV) replication and viral antigen production after cessation of all treatments for CHB due to the… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatitis B
What is being tested?
GSK3389404
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
78 participants
Where
21 sitesin 6 countries
Study dates
14 Feb 2017to 6 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject is able to understand and is capable of giving written informed consent, is willing to comply with protocol requirements, instructions and protocol-stated restrictions, and is likely to complete the study as planned.
  • Between 18 and 70 years of age, inclusive, at the time of signing the informed consent form.
  • A body mass index (BMI) between 18 to 30 kilogram (Kg)/meter (m^2), inclusive.
  • Male or female if they satisfy the following: All females must meet the following criteria: Non-pregnant (as confirmed by a negative serum Human Chorionic Gonadotropin [hCG] test); AND Non-lactating at screening and prior to dosing; AND For Part 2, females of reproductive potential (FRP) must agree to follow (or confirm that they have and are currently following) one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP from at least 28 days prior to the first dose of study treatment until Follow-up visit Day 169 in conjunction with partner's use of male condom. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. For females of non-reproductive potential at least one of the following conditions must apply: Premenopausal females without reproductive potential defined by Documented salpingectomy, Hysterectomy or Documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea; A blood sample for simultaneous Follicle-Stimulating Hormone (FSH) and estradiol levels may be collected at the discretion of the investigator or site to confirm non-reproductive potential; Male subjects with a female partner of child-bearing potential must agree to meet one of the contraception requirements from the time of first dose of study treatment until Follow-up visit Day 169; Vasectomy; Male condom plus partner's use of one of the contraceptive options below that meets the Standard Operating Procedure (SOP) effectiveness criteria including a <1 percent rate of failure per year, as stated in the product label: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Combined estrogen and progestogen oral contraceptive, Injectable progestogen, Contraceptive vaginal ring, or Percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. Male subjects must refrain from donating sperm from the time of first dose of study treatment until Follow-up visit Day 169.
  • Documented chronic HBV infection >=6 months prior to screening.
  • Subjects with HBV treatment history as follows: Part 1: Treatment naive or have had prior treatment with interferon (pegylated or non pegylated) that must have ended at least 6 months prior to the Baseline visit (Day 1 pre-dose) and/or nucleos(t)ide analogue therapy that must have ended at least 6 months prior to the Baseline visit or currently receiving stable nucleos(t)ide analogue therapy, 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. Part 2: Subjects with CHB receiving stable nucleos(t)ide analogue therapy, 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. Subjects with prior treatment with interferon (pegylated or non-pegylated) must have ended treatment at least 6 months prior to the Baseline visit (Day 1 pre-dose).
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  • Plasma or serum HBV DNA concentration: treatment naïve subjects or subjects not currently receiving treatment, there is no minimum HBV DNA requirement; Subjects who are receiving stable nucleos(t)ide analogue therapy must be adequately suppressed, defined as plasma or serum HBV DNA <lower limit of quantification (LLOQ)
  • Plasma or serum HBsAg concentration >50 IU/mL.
  • Alanine aminotransferase (ALT) concentration: ALT < 5 X Upper Limit of Normal (ULN) for treatment naïve subjects and for subjects who are not currently receiving treatment. ALT <=2 times ULN for subjects who are receiving stable nucleos(t)ide analogue therapy.

Who cannot join

  • Medical history: History of or active diagnosis of moderate to severe liver disease other than CHB, such as autoimmune hepatitis, non alcoholic steatohepatitis, hemochromatosis, or liver failure. History or other clinical evidence of significant or unstable cardiac disease (e.g., prolonged QT syndrome [torsade de pointes], angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease and/or clinically significant ECG abnormalities). Uncontrolled or history of difficult to control hypertension. History of, or active diagnosis of, primary or secondary renal disease (e.g., renal disease secondary to diabetes, hypertension, vascular disease, etc.). History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis and polyarteritis nodosa). History of bleeding diathesis or coagulopathy. History of or suspected presence of vasculitis. History of Gilbert's Syndrome. History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer), subjects under evaluation for possible malignancy are not eligible.
  • History of/sensitivity to GSK3389404 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
  • Confirmed or suspected hepatocellular carcinoma (HCC) as evidenced by: Alpha-fetoprotein concentration >=200 nanogram (ng)/mL. 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.
  • Liver cirrhosis or evidence of cirrhosis as determined by any of the following: Positive liver biopsy (i.e., Metavir Score F4) within 12 months of screening. Fibroscan >12 kilopascals (kPa) within 12 months of screening. AST-Platelet Index (APRI) >2 and FibroSure result >0.7 within 12 months of screening and Investigator judgment. For subjects without a test for cirrhosis in the above timeframes, APRI and FibroSure should be performed during the screening period to rule out cirrhosis.
  • Hepatitis C Virus (HCV) co-infection.
  • Human Immunodeficiency Virus (HIV) co-infection.
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  • Hepatitis D Virus (HDV) co-infection.
  • Laboratory results as follows: Total bilirubin concentration >1.25 X ULN. Serum albumin concentration <3.5 grams (g)/deciliter (dL). International normalized ratio (INR) >1.25. Platelet count <140 X 10^9/L. Serum creatinine concentration greater than the ULN. Glomerular Filtration Rate (GFR) <90 mL/min as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula. Subjects with GFR <90 mL/min but >= 60 mL/min may be considered after consultation with the GlaxoSmithKline medical monitor. 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 in cases where subjects 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 subject does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the PPD or GSK medical monitor, or designee.
  • Positive test for blood in urine. In the event of a positive test, the test may be repeated once, and if repeat is negative or if urine microscopy reveals <5 RBC per High-Power Field (HPF), the subject is considered eligible.
  • Fridericia's QT correction formula (QTcF) >=450 milliseconds (msec) (single ECG at screening shows QTcF >=450 msec, a mean of triplicate measurements should be used to confirm that subject meets exclusion criterion).
  • 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.
  • Current alcohol use as judged by investigator to potentially interfere with participant compliance.
  • A positive pre-study treatment screen and an unwillingness to refrain from use of illicit drugs (or substances with abuse potential) and adhere to other protocol-stated restrictions while participating in the study [The screen refers to illicit drugs and substances with abuse potential. Medications that are used by the subject as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria]. .
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • The subject 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).
  • Prior treatment with any non-GSK oligonucleotide or small interfering ribonucleic acid (RNA) (siRNA) within 12 months prior to the first dosing day or prior treatment with GSK oligonucleotide within 3 months prior to the first dosing day.
  • Pregnant or lactating females at screening and prior to dosing.
  • For Part 1, females of reproductive potential.

Trial locations and contacts

21 sites in 6 countries.

21 sites in 6 countries

Japan6 sites

  • GSK Investigational Site

    Aichi, 467-8602

  • GSK Investigational Site

    Hiroshima, 734-8551

  • GSK Investigational Site

    Hokkaidou, 060-0033

  • GSK Investigational Site

    Kanagawa, 213-8587

  • GSK Investigational Site

    Tokyo, 105-8470

  • GSK Investigational Site

    Tokyo, 180-8610

Other trials in Japan

China5 sites

  • GSK Investigational Site

    Beijing, 100015

  • GSK Investigational Site

    Beijing, 100050

  • GSK Investigational Site

    Beijing, 100069

  • GSK Investigational Site

    Guangzhou, Guangdong, 510150

  • GSK Investigational Site

    Shanghai, 200025

Other trials in China

South Korea5 sites

  • GSK Investigational Site

    Busan, 49241

  • GSK Investigational Site

    Busan, 614-735

  • GSK Investigational Site

    Daegu, 41944

  • GSK Investigational Site

    Gyeonggi-do, 15355

  • GSK Investigational Site

    Seoul, 3080

Other trials in South Korea

Philippines2 sites

  • GSK Investigational Site

    Cebu, 6000

  • GSK Investigational Site

    Makati City, 1229

Other trials in Philippines

Singapore2 sites

  • GSK Investigational Site

    Singapore, 119074

  • GSK Investigational Site

    Singapore, 169608

Other trials in Singapore

Hong Kong1 site

  • GSK Investigational Site

    Pokfulam

Other trials in Hong Kong

About this study

Official title: A Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Dose and Multiple Doses of GSK3389404 in Chronic Hepatitis B Subjects

GSK3389404 is being developed for the treatment of CHB virus infection. The development goal for GSK3389404 is the establishment of a finite duration treatment that results in sustained suppression of hepatitis B virus (HBV) replication and viral antigen production after cessation of all treatments for CHB due to the restoration of a functional immune response in the absence of high antigen levels. This study is a multicenter, randomized double-Blind (sponsor un-blinded in Part 1), Placebo-controlled Study which will evaluate the safety, tolerability, PK, and PD profile of GSK3389404 in subjects with CHB and aim to establish proof-of-mechanism. The study will be conducted in two parts. Part 1 plans to enroll subjects primarily from the Asia-pacific region, including Japan and will be conducted as a single ascending dose (SAD) study with 5 planned cohorts ranging from 30 milligram (mg) to a maximum of 240 mg GSK3389404. Within each cohort, subjects will be randomized to receive either GSK3389404 or placebo in a 3:1 ratio. Cohorts A, B, C, C1, and D will be conducted in a sequential fashion; Cohort C1 is an optional cohort and may be dosed after Cohort C or in parallel with Cohort D. Part 2 will be conducted as a multiple-dose, dose-ranging study. Subjects will be randomized to different parallel dose levels and regimens or placebo. The dose levels of Part 2 will be selected after a review of Part 1 safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) data. The treatments selected are 60 mg GSK3389404 weekly, 120 mg GSK3389404 bi-weekly, 120 mg GSK3389404 weekly or placebo. An optional Japanese part-2 sub-study is planned. The total study duration for part 1 including screening, treatment, and post-treatment follow-up, will not be expected to exceed 13 weeks for each subject and for part 2, including screening, treatment and post-treatment follow-up, will not be expected to exceed 65 weeks for each subject.

Conditions
Hepatitis B
Being tested
GSK3389404, Placebo
Keywords
Pharmacokinetics, Safety, Pharmacodynamics, Efficacy, Chronic Hepatitis B, GSK3389404
Medical subject headings
Hepatitis B, Hepatitis B, Chronic

What participants receive

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

  • GSK3389404Drug

    GSK3389404 is available as Clear colorless to slightly yellow solution for injection.

  • PlaceboDrug

    Placebo is available as a Clear colorless solution.

Study groups in NCT03020745
Study groupRoleWhat they receive
Part 1, Cohort A : GSK3389404 30 mg SC or PlaceboExperimentalEnrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 30 mg or matching placebo
Receives: Drug: GSK3389404; Drug: Placebo
Part 1, Cohort B: GSK3389404 60 mg SC or PlaceboExperimentalEnrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 60 mg or matching placebo
Receives: Drug: GSK3389404; Drug: Placebo
Part 1, Cohort C: GSK3389404 120 mg SC or PlaceboExperimentalEnrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 120 mg or matching placebo
Receives: Drug: GSK3389404; Drug: Placebo
Part 1, Cohort C1 (optional): GSK3389404 120 mg SC or PlaceboExperimentalEnrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 120 mg or matching placebo
Receives: Drug: GSK3389404; Drug: Placebo
Part 1, Cohort D: GSK3389404 </= 240 mg SC or PlaceboExperimentalEnrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 <= 240 mg or matching placebo
Receives: Drug: GSK3389404; Drug: Placebo
Part 2: GSK3389404 or placebo SCExperimentalEnrolled subjects will receive different parallel dose level and regimens of GSK3389404 or placebo SC at dose determined in part 1. The treatments for Part 2 are 60 mg GSK3389404 weekly, 120 mg bi-weekly GSK3389404, 120 mg GSK3389404 weekly or placebo.
Receives: Drug: GSK3389404; Drug: Placebo

What is being measured

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

  1. Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points

    SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30

  2. Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 169-Interim Analysis)

    SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  3. Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 450-Optional Follow-up)

    SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 270 and Day 450

  4. Part 1: Change From Baseline in Heart Rate at Indicated Time Points

    Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30

  5. Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 169-Interim Analysis)

    Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  6. Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 270 and Day 450

  7. Part 1: Change From Baseline in Respiratory Rate at Indicated Time Points

    Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 3, 8 and 30

  8. Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 169-Interim Analysis)

    Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  9. Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 270 and Day 450

  10. Part 1: Change From Baseline in Body Temperature at Indicated Time Points

    Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 3, 8 and 30

  11. Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 169-Interim Analysis)

    Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  12. Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Day 270 and Day 450

  13. Part 1: Number of Participants With Abnormal Findings in Physical Examination

    Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

    Measured: Up to Day 60

  14. Part 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 169-Interim Analysis)

    Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

    Measured: Up to Day 169

  15. Part 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 450-Optional Follow-up)

    Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

    Measured: Up to Day 450

  16. Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters

    Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, Activated partial thromboplastin time (aPTT), Prothrombin international normalized ratio (INR) and Prothrombin time (PT). Laboratory parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 60

  17. Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 169-Interim Analysis)

    Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, aPTT, Prothrombin INR and PT. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 169

  18. Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 450-Optional Follow-up)

    Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, aPTT, Prothrombin INR and PT. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 450

  19. Part 1: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points

    Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 60

  20. Part 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 169

  21. Part 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were planned to be collected from participants to evaluate change from Baseline in complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  22. Part 1: Change From Baseline in Complement Bb Level at Indicated Time Points

    Blood samples were collected from participants to assess complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 60

  23. Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 169

  24. Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were collected from participants to evaluate change from Baseline in complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  25. Part 1: Change From Baseline in Complement C5a Level at Indicated Time Points

    Blood samples were collected from participants to assess complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 60

  26. Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 169

  27. Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were collected from participants to evaluate change from Baseline in complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  28. Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters

    Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low) and Urate. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 60

  29. Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 169-Interim Analysis)

    Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 169

  30. Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 450-Optional Follow-up)

    Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

    Measured: Up to Day 450

  31. Part 1: Change From Baseline in Urine Albumin at Indicated Time Points

    Urine samples were collected from participants to assess urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)

  32. Part 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 169-Interim Analysis)

    Urine samples were collected from participants to assess urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169

  33. Part 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Urine samples were planned to be collected from participants to evaluate change from Baseline in urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  34. Part 1: Change From Baseline in Urine Creatinine at Indicated Time Points

    Urine samples were collected from participants to assess urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)

  35. Part 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 169-Interim Analysis)

    Urine samples were collected from participants to assess urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169

  36. Part 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Urine samples were planned to be collected from participants to evaluate change from Baseline in urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  37. Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) at Indicated Time Points

    Urine samples were collected from participants to assess urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)

  38. Part 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 169-Interim Analysis)

    Urine samples were collected from participants to assess urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  39. Part 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Urine samples were planned to be collected from participants to evaluate change from Baseline in urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  40. Part 1: Change From Baseline in Urine Specific Gravity at Indicated Time Points

    Urine samples were collected from participants to assess urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)

  41. Part 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 169-Interim Analysis)

    Urine samples were collected from participants to assess urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  42. Part 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Urine samples were planned to be collected from participants to evaluate change from Baseline in urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  43. Part 1: Change From Baseline in Urobilinogen at Indicated Time Points

    Urine samples were collected from participants to assess urobilinogen levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)

  44. Part 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 169-Interim Analysis)

    Urine samples were collected from participants to assess urobilinogen levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  45. Part 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Urine samples were planned to be collected from participants to evaluate change from Baseline in urobilinogen. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  46. Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

    Electrocardiograms were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.

    Measured: Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30

  47. Part 2: Number of Participants With Abnormal ECG Findings (Up to Day 169-Interim Analysis)

    Electrocardiogram were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. CS and NCS abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.

    Measured: Days 29, 57, 85 and 169

  48. Part 2: Number of Participants With Abnormal ECG Findings (Up to Day 450-Optional Follow-up)

    ECGs were planned to be obtained after 5 minutes of rest in the semi-supine or supine position using ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals.

    Measured: Days 270, 360 and 450

  49. Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.

    Measured: Up to Day 60

  50. Part 2: Number of Participants With AEs and SAEs (Up to Day 169-Interim Analysis)

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.

    Measured: Up to Day 169

  51. Part 2: Number of Participants With AEs and SAEs (Up to Day 450-Optional Follow-up)

    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.

    Measured: Up to Day 450

  52. Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for GSK3389404

    Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  53. Part 2: AUC (0-t) for GSK3389404

    Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  54. Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for GSK3389404

    Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  55. Part 2: AUC (0-infinity) for GSK3389404

    Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  56. Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3389404

    Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  57. Part 2: Cmax of GSK3389404

    Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  58. Part 1: Time to Achieve Cmax (Tmax) of GSK3389404

    Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  59. Part 2: Tmax of GSK3389404

    Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  60. Part 1: Apparent Terminal Phase Half-life(t1/2) of GSK3389404

    Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  61. Part 2: t1/2 of GSK3389404

    Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  62. Part 1: Apparent Subcutaneous Plasma Clearance (CL/F) of GSK3389404

    Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  63. Part 2: CL/F of GSK3389404

    Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  64. Part 1: Number of Participants Achieving Response Rate (RR) Based on Reduction of Hepatitis B Surface Antigen (HBsAg) Level From Baseline

    The RR was based on the proportion of participants with at least a 1.5 logarithm to the base 10 (log10) international units per milliliter (IU/mL) reduction of HBsAg levels from Baseline at any time up to Day 60. Number of participants who achieved >1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 60 are presented.

    Measured: Up to Day 60

  65. Part 2: Number of Participants Achieving RR Based on Reduction of HBsAg Level From Baseline

    The RR was based on the proportion of participants with at least a 1.5 log10 IU/mL reduction of HBsAg levels from Baseline at any time up to Day 85. Number of participants who achieved >1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 85 are presented.

    Measured: Up to Day 85

Secondary outcomes (17)

  1. Part 1: Change From Baseline in log10 Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Indicated Time Points

    Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose), Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60

  2. Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose) and Up to Day 169

  3. Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose) and Up to Day 450

  4. Part 1: Change From Baseline in log10 Hepatitis B Virus Surface Antigen (HBsAg) Levels in Plasma at Indicated Time Points

    Blood samples were collected from participants to assess HBsAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60

  5. Part 2: Change From Baseline in log10 HBsAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess HBsAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  6. Part 2: Change From Baseline in log10 HBsAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were collected from participants to assess HBsAg level. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450

  7. Part 1: Change From Baseline in log10 Hepatitis B Virus E-antigen (HBeAg) Levels in Plasma at Indicated Time Points

    Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60

  8. Part 2: Change From Baseline in log10 HBeAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

    Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169

  9. Part 2: Change From Baseline in log10 HBeAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

    Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

    Measured: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450

  10. Part 1: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)

    Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  11. Part 2: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)

    Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  12. Part 1: Cmax of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  13. Part 2: Cmax of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  14. Part 1: Tmax of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  15. Part 2: Tmax of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

  16. Part 1: t1/2 of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30

  17. Part 2: t1/2 of GSK3389404 Metabolite (ISIS 505358)

    Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

    Measured: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

Timeline

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

  1. First posted13 Jan 2017 (estimated)
  2. Study start14 Feb 2017
  3. Primary completion28 Jan 2019
  4. Study completion6 Nov 2019

Resources

More details

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

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03020745
Sponsor's protocol ID
205670
Status last verified
Sep 2020
First submitted
5 Dec 2016
Last updated
1 Oct 2020
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request Site

Publications

  • Han K, Theodore D, McMullen G, Swayze E, McCaleb M, Billioud G, Wieland S, Hood S, Paff M, Bennett CF, Kwoh TJ. Preclinical and Phase 1 Assessment of Antisense Oligonucleotide Bepirovirsen in Hepatitis B Virus-Transgenic Mice and Healthy Human Volunteers: Support for Clinical Dose Selection and Evaluation of Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses. Clin Pharmacol Drug Dev. 2022 Oct;11(10):1191-1202. doi: 10.1002/cpdd.1154. Epub 2022 Aug 16.

    PubMed 35971951

  • Yuen MF, Heo J, Kumada H, Suzuki F, Suzuki Y, Xie Q, Jia J, Karino Y, Hou J, Chayama K, Imamura M, Lao-Tan JY, Lim SG, Tanaka Y, Xie W, Yoon JH, Duan Z, Kurosaki M, Park SJ, Labio ME, Kumar R, Kweon YO, Yim HJ, Tao Y, Cremer J, Elston R, Davies M, Baptiste-Brown S, Han K, Campbell FM, Paff M, Theodore D. Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy. J Hepatol. 2022 Oct;77(4):967-977. doi: 10.1016/j.jhep.2022.05.031. Epub 2022 Jun 15.

    PubMed 35714812

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK3389404 in people with Hepatitis B, run by GlaxoSmithKline at 21 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Japan, China, South Korea, Philippines, Singapore and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points (time frame: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30). The study lists 65 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03020745, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2020.

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