B-Fine: An open label, single arm study to mechanistically interrogate the therapeutic effect of GSK3228836 in patients with Chronic Hepatitis B via intrahepatic immunophenotyping

Functional cure of CHB occurs in a small percentage of patients on NA therapy
alone. The high rate of relapse in these patients is hypothesised to be due to
their inability to raise an effective immune response to the virus in the
presence of high circulating levels of HBsAg. GSK3228836, was designed to
inhibit the synthesis of HBsAg.Which may lead to (a higher percentage of
patients with) functional cure of HBV.

B-Fine is an exploratory study of the therapeutic mechanism of GSK3228836 in
participants with chronic hepatitis B (CHB) on stable nucleos(t)ide therapy.
The study will investigate the virologic and immunologic correlates of HBsAg
loss observed in participants when treated for 12 weeks with 300 mg
GSK3228836. Repeat fine needle aspirates of the liver will be performed to
enable analysis of liver-resident immune cells to investigate any
immunomodulatory properties of GSK3228836 and to study the biology of
underlying treatment-associated liver flares. Longitudinal analyses of
blood-borne inflammatory signatures and virological assessments of CHB
infection will be performed in parallel.

Primary objective:
To assess the effect of 12 weeks of GSK3228836 on serum hepatitis B virus
surface antigen (HBsAg) levels in participants with CHB

Secondary
Efficacy:
To assess sustainability of serum HBsAg loss by GSK3228836 for up to 24 weeks
off-treatment
To assess sustainability of serum HBsAg and HBV DNA loss by GSK3228836 for up
to 24 weeks off treatment.
To assess the effect of 12 weeks GSK3228836 on biomarkers and virus-specific
antibody responses

The study consists of a single treatment arm with 300 mg GSK3228836 for 12
weeks (loading schedule on Day 4 and Day 11). Participants will continue to
receive their nucleoside therapy.

The total duration of the study, including screening, treatment and
post-treatment follow-up, is not expected to exceed 45 weeks.
o 45-day screening window. Eligible participants who fall out of the 45-day
window may be re-screened.
o Up to 1 week of pre-treatment assessments (including baseline FNA)
o 12 weeks treatment with GSK3228836
o 24 weeks post treatment follow-up (+ up to 10 days)

There are no plans for dose adjustments. Individual dose adjustments for
safety are outlined in the monitoring/stopping criteria.

Two 1 ml subcutaneous injections per visit, 14x

Known side effects of GSK3228836 based on past studies these side effects are
considered very common (may affect more than 1 in 10 people):
• Reaction to injections including: pain, redness, swelling, and itching at or
near the site of injection
• Abnormal blood liver tests
• Increased body temperature, headaches, feeling sick, muscle pain

Other risks with GSK3228836, they are potential risks but not known as side
effects for GSK3228836.
• Decreased platelet count/bleeding: in previous human studies, GSK3228836 did
decrease platelet counts a little, but did not have any bleeding events.
• Drug induced vascular inflammation and complement activation, this effect has
been seen in some animal studies with medicines like GSK3228836, but not in
human studies with GSK3228836.
• Drug induced kidney injury, this effect has been seen in studies with
medicines like GSK3228836, but not with GSK3228836.

Risks associated with stopping GSK3228836 treatment
• In hepatitis B patients, stopping nucleoside therapy has been known to cause
abnormal blood liver tests. It is not known if stopping the study treatment
(GSK3228836) will also cause increase in the results of blood liver tests
• Risk of the development of resistance to study drug
• With any drug against hepatitis B virus, there is a risk that the virus in
your body will become resistant

Risks associated with study procedures/tests
• Blood drawls: giving blood might hurt ,give bruising, irritation or redness
from the needle. Sometimes someone feels like faint.
• ECG: a skin rash or irritation may occur where electrodes were placed

Risks and complications of FNA may include:
• Pain and discomfort located at or near the puncture site and radiating
upwards toward the right shoulder region, which may last for several hours
after the procedure
• Bleeding at the biopsy site
• Possible internal bleeding for up to a few hours after the procedure
(extremely rare - less than 1 in 10,000)
• Infections at the biopsy site or internal organs (extremely rare - less than
1 in 10,000
• Puncture of internal organs (gall bladder, lung, intestine or kidney) (less
than 1 in 1,000),
• Significant bleeding requiring a blood transfusion or surgery to control the
bleeding (extremely rare - less than 1 in 10,000),