Status:
ACTIVE_NOT_RECRUITING
Study of GSK3965193 in Healthy Participants and Participants Living With Chronic Hepatitis B Infection
Lead Sponsor:
GlaxoSmithKline
Conditions:
Hepatitis B
Eligibility:
All Genders
18-65 years
Phase:
PHASE1
PHASE2
Brief Summary
This Phase 1/2a multiple part study is a first time-in-human (FTIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of single (Part 1) and repeat doses (Part 2) of GSK39...
Eligibility Criteria
Inclusion
- Parts 1 and 2: Participants between 18 and 55 years of age inclusive, at the time of signing the informed consent.
- Parts 3 and 4: Participants between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Body weight \>=50 kilograms (kg) and body mass index within the range 18-32 kilograms per square meter (kg/m\^2) (inclusive).
- Male or female participant: a. Parts 1 and 2: woman of nonchildbearing potential only. b. Parts 3 and 4: woman of nonchildbearing potential or woman of child-bearing potential who is not pregnant or breastfeeding and is using a contraceptive method that is highly effective.
- Capable of giving signed informed consent.
- Additional Inclusion Criteria for PLWCHB (Parts 3 and 4).
- Participants who have documented chronic hepatitis B virus (HBV) infection \>=6 months prior to screening.
- Participants currently receiving stable NA therapy (e.g., tenofovir disoproxil, tenofovir alafenamide, entecavir).
- Plasma or serum HBsAg concentration \>100 IU/mL.
- Plasma or serum HBV deoxyribonucleic acid (DNA) concentration \<90 IU/mL.
- Hepatitis B virus e-antigen (HBeAg) positive or negative.
- Alanine aminotransferase (ALT) \<=2 times the upper limit of normal (ULN)
Exclusion
- Exclusion Criteria for Healthy Participants:
- Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M \[IgM\]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening
- A current diagnosis of migraine headache
- ALT \>1 times ULN.
- Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\])
- Corrected QT interval (QTc) \>450 milliseconds (msec)
- Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19)
- Participants with known COVID-19 positive contacts in the past 14 days.
- For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy
- Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of \>5 pack years
- Exclusion Criteria for PLWCHB:
- Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
- Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
- History of or suspected liver cirrhosis and/or evidence of cirrhosis.
- Diagnosed or suspected hepatocellular carcinoma.
- History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
- History of vasculitis or presence of symptoms and signs of potential vasculitis \[e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause\] or history/presence of other diseases Exclusion Criteria for Healthy Participants:
- Positive Hepatitis A virus antibody (HAV Ab immunoglobulin M \[IgM\]), or positive for HBV, hepatitis C virus (HCV) or human immunodeficiency virus (HIV) at screening.
- A current diagnosis of migraine headache
- ALT \>1 times ULN.
- Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
- Corrected QT interval (QTc) \>450 milliseconds (msec).
- Signs and symptoms suggestive of Coronavirus Disease 2019 (COVID-19).
- Participants with known COVID-19 positive contacts in the past 14 days.
- For participants in Part 2A: i. Personal history or family history of peripheral neuropathy. ii. A score ≥4 on the Toronto clinical scoring system for polyneuropathy.
- Current or previous use of tobacco- or nicotine-containing products (for example (e.g.) cigarettes, nicotine patches or electronic devices) within 6 months before screening and/or have a smoking pack history of \>5 pack years
- Exclusion Criteria for PLWCHB:
- Clinically significant abnormalities affecting physical or mental health in medical history or on physical examination, aside from chronic HBV infection.
- Co-infection with or past history of HCV, HIV or Hepatitis D virus (HDV).
- History of or suspected liver cirrhosis and/or evidence of cirrhosis.
- Diagnosed or suspected hepatocellular carcinoma.
- History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer).
- History of vasculitis or presence of symptoms and signs of potential vasculitis \[e.g., vasculitic rash, skin ulceration, repeated blood detected in urine without identified cause\] or history/presence of other diseases that may be associated with vasculitis condition (e.g., systemic lupus erythematosus, rheumatoid arthritis, relapsing polychondritis, mononeuritis multiplex).
- History of extrahepatic disorders possibly related to HBV immune conditions (e.g., nephrotic syndrome, any type of glomerulonephritis, polyarteritis nodosa, cryoglobulinaemia, uncontrolled hypertension).
- History of alcohol or drug abuse/dependence: a. Current alcohol use as judged by investigator to potentially interfere with participant compliance. b. History of or current drug abuse/dependence as judged by the investigator to potentially interfere with participant compliance.
- History or other evidence of bleeding from esophageal varices.
- Documented history or other evidence of metabolic liver disease within 1 year of randomization.
- Personal history or family history of peripheral neuropathy.
- A score \>4 on the Toronto clinical scoring system for polyneuropathy.
- History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral corticosteroids, interferon or pegylated interferon) within the 3 months prior to randomization or the expectation that such treatment will be needed at any time during the study.
- Abnormal and clinically significant 12-lead ECG finding.
- Currently taking, or taken within 3 months prior to randomization, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (≤2 weeks) or topical/inhaled steroid use.
- Participants requiring anti-coagulation therapies.
- Prior treatment with any oligonucleotide or small interfering RNA (siRNA) within 12 months prior to the first dosing day.
- Positive test for COVID-19 infection.
Key Trial Info
Start Date :
April 14 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 3 2026
Estimated Enrollment :
74 Patients enrolled
Trial Details
Trial ID
NCT05330455
Start Date
April 14 2022
End Date
April 3 2026
Last Update
August 19 2025
Active Locations (16)
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1
GSK Investigational Site
Calgary, Alberta, Canada, T2N 4Z6
2
GSK Investigational Site
Ottawa, Ontario, Canada, K1H 8L6
3
GSK Investigational Site
Grenoble, France, 38043
4
GSK Investigational Site
Lyon, France, 69004