主要目的為監測直到最後一次回診期間所發生的AEs和SAEs。

皮下注射劑

GSK5926371

220

2mg/ml

為監測直到最後一次回診期間所發生的AEs和SAEs，藉以評估逐步增加GSK5926371皮下注射劑量的安全性和耐受性。

- Part 1 will enroll adult participants with systemic lupus
erythematosus (SLE) or rheumatoid arthritis (RA).
- Part 2 will enroll adult participants with SLE, RA, idiopathic
inflammatory myopathies (IIM) or Sjogren’s disease (SjD).
- Participants must be 18 to 70 years of age inclusive at the time of
signing the informed consent form.
- Body mass index (BMI) between 18-35 kilograms per square
meter (kg/m^2) inclusive with a body weight of greater than or
equal to (>=) 45 kilograms (kg).
- A female participant is eligible to participate if she is not pregnant
or breastfeeding, and one of the following conditions applies:
- Is a participant of non-childbearing potential (PONCBP), OR
- Is a participant of childbearing potential (POCBP) and using a
contraceptive method that is highly effective, with a failure rate of
less than (<) 1 percent (%), 28 days prior to and during the study
intervention period and for at least 28 weeks after the first dose
of GSK5926371. The investigator should evaluate potential for
contraceptive method failure (e.g. noncompliance, recently
initiated) in relationship to the first dose of study intervention.
A POCBP must have a negative highly sensitive pregnancy test
(urine or serum, as required by local regulations) within 24 hours
before the first dose of study intervention.
If a urine test cannot be confirmed as negative (e.g. an
ambiguous result), a serum pregnancy test is required. In such
cases, the participant must be excluded from participation if the
serum pregnancy result is positive.
- Signed and dated informed consent form indicating that the
participant is willing and able to comply with hospitalization, clinic
visits and scheduled study assessments as detailed in the
protocol.

- Any acute, severe autoimmune disease-related flare before, or
during the Screening Period (up to and including Day 1) that
needs immediate treatment or is expected to require escalation of
treatment to prohibited medications for the duration of the study.
- Significant allergies to humanized monoclonal antibodies or
significant sensitivity to any constituents of the study drug
(including excipients).
- Clinically significant multiple or severe drug allergies, intolerance
to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major,
linear immunoglobulin A (IgA) dermatosis, toxic epidermal
necrolysis, and exfoliative dermatitis).
- Have clinical evidence of significant unstable or uncontrolled
acute or chronic diseases not due to the autoimmune condition
under study (i.e., cardiovascular, pulmonary, hematologic,
gastrointestinal, hepatic, renal, or infectious diseases) and/or a
planned surgical procedure, which, in the opinion of the
investigator, could confound the results of the clinical study or put
the participant at undue risk.
- Have any other clinically significant abnormal laboratory value,
that in the opinion of the investigator, is capable of significantly
altering the absorption, metabolism, or elimination of the clinical
study intervention; or constitutes a risk when taking the clinical
study intervention or interferes with the interpretation of the clinical
study data.
- Participant has a diagnosis of primary or acquired
immunodeficiency, except for selective IgA deficiency.
- Have an acute or chronic infection including requiring
management as follows:
- An acute infection within 2 weeks of dosing on Day 1.
- An active infection requiring current systemic antibiotic, antiviral
or anti-fungal treatment with the exception of topical treatments
for fungal nail infections. Prophylactic medications are permitted.
- History of, or currently being treated for, a clinically significant
recurrent or chronic infection (except for minor localized
infections, for example tinea pedis).
- Any opportunistic infections within past 3 years. Uncomplicated
herpes zoster, localized herpes simplex virus, and oral
candidiasis are not considered as opportunistic infections for this
purpose.
- Herpes zoster within 3 months before screening.
- A serious infection requiring treatment with intravenous
(IV)/intramuscular (IM) antibiotics and/or hospitalization if the last
dose of antibiotics or the hospital discharge date was within 30
days of the first day of dosing (Day 1).
- History of a serious infection associated with low serum
immunoglobulin levels.
- Evidence of active or latent tuberculosis (TB) as documented by
medical history and examination (including chest X-rays [CXR], if
available), and a positive (not indeterminate) TB test such as
QuantiFERON-TB Gold Plus test. In cases where the
QuantiFERON test is indeterminate, the participant may have the
test repeated once, but if the test remains indeterminate further
investigation may be required including CXR (posteroanterior [PA]
and lateral) in order to exclude TB. Note: The QuantiFERON-TB
Gold Plus test can only be used in countries where it is licensed,
and the use of this test is dependent on previous treatment(s).
This test may not be suitable if previous treatment(s) produced
significant immunosuppression.
- Confirmed progressive multifocal leukoencephalopathy (PML)
within 12 months or has unexplained or deteriorating neurologic
signs and symptoms.
- History or positive test at Screening for human immunodeficiency
virus (HIV).
- History of clinically significant neurological or psychiatric disorder
including history of epilepsy, dementia, increased risk of suicide
as judged by the investigator or major depression deemed to
interfere with study assessments, or a history of intracranial
hemorrhage.
- Solid or hematological malignancy or a history of malignancy (in
the past 5 years) of except for basal cell or squamous cell in situ
skin carcinomas, cervical intraepithelial neoplasia (CIN) or
carcinoma in situ of the cervix that have been resected with no
evidence of metastatic disease for 3 years. The investigator
should also ensure that occult malignancy associated with the
autoimmune condition under study has been adequately ruled out
prior to screening (for example, malignancy-associated
dermatomyositis).
- History of hematological or solid organ transplant.
- Live or live-attenuated vaccine(s) within 30 days before Screening
or plans to receive such vaccines during the screening period or
during the clinical study.
- Current or prior treatment with any of the medications specified
below during the relevant exclusion periods prior to Day 1. The
following medications are prohibited from the periods before the
study, until the last study visit:
- IV or IM dose of corticosteroids within 5 weeks of Day 1.
- Any T-cell engager (TCE) including blinatumomab,
mosunetuzumab or other approved or investigational T cell
engagers within 12 months of Day 1.
- Chimeric antigen receptor (CAR)-T-cell treatment, at any time.
- B-cell depleting agents, including but not limited to anti-CD20
(e.g. Rituximab, Obinutuzumab, Ocrelizumab), anti-CD38 (e.g.
Daratumumab, TAK079, MOR202, isatuximab) within 4 months
of Day 1.
- Belimumab within 8 weeks of Day 1.
- Anifrolumab within 8 weeks of Day 1.
- Oral or IV cyclophosphamide within 12 weeks of Day 1.
- Immune-Modulating Biologic agents, including anti-tumor
necrosis factor (TNF) therapy (e.g., adalimumab and
etanercept), abatacept, and interleukin (IL)-1 receptor antagonist
[anakinra] or IL-6 receptor antagonist (tocilizumab) within 4
weeks of Day 1. Except infliximab, golimumab, and certolizumab
within 8 weeks of Day 1. (NOTE: tocilizumab is permitted for
cytokine release syndrome (CRS) Grade 3/4 management after
dosing)
- Small molecule inhibitors, including tyrosine kinase 2 inhibitor
(TYK2i, Deucravacitinib); inhibitors of Janus kinases (JAKis,
baricitinib, tofacitinib, upadacitinib, filgotinib); or Bruton tyrosine
kinase inhibitors (ibrutinib, fenebrutinib) within 4 weeks of Day 1.
- IV immunoglobulin within 8 weeks of Day 1.
- Plasmapheresis within 8 weeks of Day 1.
- Current enrolment or past participation in any other clinical study
involving an investigational study treatment (including
investigational vaccines) within 3 months or 5 half-lives of the investigational drug or twice the duration of pharmacological
activity (whichever is longer) before Day 1.
- Contra-indications to prophylactic medications for CRS
(corticosteroid, ant histamines and antipyretics), or CRS rescue
medication (tocilizumab or IV corticosteroids).
- Current drug or alcohol dependence, or a history of drug or
alcohol abuse or dependence within 12 months before Day 1.
- Alanine transaminase (ALT) greater than (>) 1.5 x upper limit of
normal (ULN).
- Total bilirubin > 1.5 x ULN; Participants with Gilbert’s syndrome
can be included with total bilirubin > 1.5 x ULN if direct bilirubin is
> 1.5 x ULN.
- Current or chronic history of liver disease or known hepatic or
biliary abnormalities (except for Gilbert's syndrome or
asymptomatic gallstones).
- Presence of hepatitis B surface antigen (HBsAg), hepatitis B core
antibody (HBcAb) or hepatitis B virus (HBV) deoxyribonucleic acid
(DNA) at screening or within 3 months prior to first dose of study
intervention.
- Positive hepatitis C antibody test result at screening or within 3
months prior to first dose of study intervention. Note: Participants
with positive hepatitis C antibody due to prior resolved disease
can be enrolled, only if a confirmatory negative hepatitis C
ribonucleic acid (RNA) test is obtained.
- Positive hepatitis C RNA test result at screening or within 3
months prior to first dose of study intervention. Note: Test is
optional and participants with negative hepatitis C antibody test
are not required to also undergo hepatitis C RNA testing.
- Corrected QT (QTc) interval > 450 milliseconds (msec) or QTc
interval > 480 msec for participants with bundle branch block.
Frederica’s formula (QT interval corrected using Fridericia’s
formula [QTcF]) should be used to calculate the corrected QT
interval. If a single electrocardiogram (ECG) at screening shows
QTcF > 450 msec (or > 480 msec for participants with bundle
branch block), a mean of triplicate measurements should be used
to confirm that participant meets exclusion criterion.