A Study of GSK4527363 in Healthy Participants, Systemic Lupus Erythematosus (SLE) Participants, Healthy Chinese, and Japanese Participants and CTD-ILD Participants

For Part A and Part C (Healthy Participants):

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent form.
• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (vital signs and 12-lead ECG).
• Part C only: Be of Japanese (Cohort C1) or Chinese (Cohort C2) ancestry. i. Born in Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2); and ii. Descendent of 2 ethnic Japanese (Cohort C1) or Chinese (Cohort C2) parents and 4 ethnic grandparents; and iii. Have lived outside Japan (Cohort C1) or China mainland, Hong Kong or Taiwan (Cohort C2) for less than 10 years at the time of screening.
• Body weight greater than or equals to (>=) 45 kilograms (kg).
• Body mass index (BMI) within the range 18-32 kilograms per square meter (kg/m^2) (inclusive).
• Male or female of non-childbearing potential For Part B (SLE participants):
• 18 to 65 years of age inclusive, at the time of signing the informed consent form
• Documented clinical diagnosis of SLE according to the (European alliance of associations of rheumatology [EULAR]/ American College of Rheumatology [ACR] SLE classification criteria)
• Body weight >= 45 kg.
• BMI within the range 18-32 kg/m^2 (inclusive).
• Male or female
• Capable of giving signed informed consent For Part D (CTD-ILD Participants)
• Participants must be 18 to 65 years of age, at the time of signing the informed consent form.
• Documented clinical diagnosis of Rheumatoid arthritis (RA), Systemic sclerosis (SSc), Idiopathic inflammatory myopathy (IIM); including polymyositis, dermatomyositis, antisynthetase syndrome, Primary Sjogren’s syndrome (pSS) or mixed connective tissue disease (MCTD) in accordance with internationally recognised classification criteria
• Documented clinical diagnosis of interstitial lung disease (ILD) as determined by historical High-resolution computed tomography (HRCT)
• Participants must be on a stable dose of therapy to manage ILD and/or underlying connective tissue disease (CTD)
• Participant has an area of skin that, in the opinion of the Investigator, would allow Subcutaneous (SC) administration of study intervention according to the protocol
• Participants must be current for all vaccinations in accordance with local guidelines, within a year of, and at least 30 days before, first dose. If local guidelines recommend seasonal influenza vaccine, this need only be administered during Flu season (October to April)
• Body weight >= 45 kg
• BMI within the range 18–32 kg/m^2 (inclusive)
• Male or female

For Part A and Part C (Healthy Participants):

• History or presence or cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders.
• A history of recurrent infections, or treatment of a chronic infection within 3 months prior to the first dose of study drug.
• Any acute infection (including upper respiratory tract infections and urinary tract infections) which has not fully resolved within four weeks before dosing.
• Symptomatic herpes zoster within 3 months prior to screening.
• Have a history of malignancy, or a strong family history of malignancies related to immunosuppression.
• Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions.
• Abnormal blood pressure.
• Evidence of active or latent Tuberculosis (TB).
• Alanine transaminase (ALT) >=1.1* Upper limit of normal (ULN).
• Total bilirubin >1.0*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >=1.5*ULN as long as direct bilirubin is less than or equal to (<=)1.5*ULN.
• Presence of Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (HBcAb) 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.
• Positive Hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
• Positive Human immunodeficiency virus (HIV) antibody test at screening.
• Prior medical history of anaphylaxis.
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec).
• Live vaccine(s) within 30 days before the dosing day or plans to receive such vaccines during the study. For Part B (SLE participants):
• Any acute, severe lupus related flare during the Screening Period that needs immediate treatment.
• Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to Systemic lupus erythematosus (SLE) which, in the opinion of the principal investigator (PI), could confound the results of the clinical study or put the participant at undue risk.
• Have an acute or chronic infection requiring management as follows: i. Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. ii. A serious infection requiring treatment with antibiotics and/or hospitalization if the last dose of antibiotics or the hospital discharge date was within 60 days of the first day of dosing (Day 1). Prophylactic anti-infective treatment is allowed.
• Evidence of active or latent TB.
• Confirmed Progressive Multifocal Leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms.
• Alanine transaminase (ALT) >2*Upper limit of normal (ULN).
• Total bilirubin >1.5*ULN; Participants with Gilbert's syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN.
• Presence of HBsAg and/or HBcAb 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.
• Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
• History or positive test at Screening for HIV.
• QTcF >450 msec.
• 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.
• Live or live-attenuated vaccine(s) within 30 days prior to Screening For Part D Participants:
• A diagnosis of ILD other than CTD-ILD and/or SLE
• History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G [IgG] less than [<]600 milligrams per decilitres [mg/dL]) or Immunoglobulin A [IgA] deficiency (IgA <10 mg/dL) at screening
• Have a Grade 2 or greater neutropenia, defined as absolute neutrophil count <1,500 /cubic millimeters (mm^3) (<1.5×10^9/liters [L]) based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at screening
• Have a Grade 2 or greater lymphopenia, defined as absolute lymphocyte count < 800 /mm3 (< 0.8 x 10^9/L) based on CTCAE v5.0 at screening
• Participants with rapidly progressive disease (absolute drop of >=10 percent (%) in Forced vital capacity (FVC) between screening and Day 1 and/or recent pulmonary hospitalisation)
• FVC <= 45% predicted at Screening
• DLCO (corrected for haemaglobin) <= 50% of predicted based on historical assessment within 6 months of Screening
• History or presence of diffuse alveolar haemorrhage (DAH) or other confounding pulmonary disease, signs or symptoms.
• Pulmonary arterial hypertension, as determined by the Investigator, prior to Day 1.
• For participants with underlying SSc only: renal crisis within 6 months prior to Day 1.
• Dependence on continuous oxygen supplementation.
• Obstructive pulmonary disease (pre-bronchodilator Forced expiratory volume in 1 second (FEV1)/FVC < 0.7).
• Major surgery (including joint surgery) within 3 months prior to Screening or planned during the duration of the study.
• Previous or planned major organ transplant (e.g. heart, lung, kidney, liver) or bone marrow transplant (e.g. autologous stem cell transplant).
• 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.
• Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to CTD-ILD (i.e., cardiovascular, metabolic, hematologic, GI, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the PI, could confound the results of the clinical study or put the participant at undue risk.
• Have an acute or chronic infection including requiring management
• Evidence of active or latent TB as documented by medical history and examination (including chest X-rays, if available), and TB testing: either a positive Tuberculin skin test (TST) or a positive (not indeterminate) TB test such as QuantiFERON-TB Gold Plus test
• Confirmed Progressive Multifocal Leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms.
• Risk of suicide, as judged by the investigator, based upon available source information, including the C-SSRS, indicating current suicidal ideation or a history of active suicidal ideation or suicide attempts.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• ALT greater than (>)2*ULN.
• Total bilirubin >1.5*ULN; Participants with Gilbert’s syndrome can be included with total bilirubin >1.5*ULN as long as direct bilirubin is >1.5*ULN.
• Presence of HBsAg and/or HBcAb 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.
• Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
• History or positive test at Screening for HIV.
• A positive confirmation of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or signs and symptoms suggestive of SARS-CoV-2 at screening or pre-dose.
• Estimated glomerular filtration rate (eGFR) <=45 milliliters per minute (mL/min) at screening
• QTcF >450 milliseconds (msec) or >480 msec for patients with bundle branch block and/or hypokalemia, and/or family history of long QT syndrome.
• Known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with diagnostic or therapeutic monoclonal antibodies.
• 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, CIN or carcinoma in situ of the cervix that have been resected with no evidence of metastatic disease for 3 years. Prior/concomitant therapy (Part D)
• Live or live-attenuated vaccine(s) within 30 days prior to Screening or plans to receive such vaccines during the Screening period or during the clinical study.
• Current or prior treatment of any of the following:
• Belimumab, at any time.
• B-cell depleting agents, including anti-CD20 (e.g. Rituximab, Obinutuzumab, Ocrelizumab), anti-CD19 (e.g. Blinatumomab) and anti-CD38 (e.g. Daratumumab, TAK079, MOR202, isatuximab) within 12 months of Day 1.
• Cell therapies, including CAR-T, TCE and others at any time.
• Immune-Modulating Biologic agents, including anti- Tumour necrosis factor (TNF) therapy (e.g., adalimumab, etanercept, infliximab), abatacept, and interleukin1 receptor antagonist (anakinra) within 3 months or 5 half-lives (whichever is longer) of screening.
• Small molecule inhibitors, including inhibitors of Janus kinases (JAKis, baricitinib, tofacitinib, upadacitinib, filgotinib); or Bruton tyrosine kinase inhibitors (ibrutinib, fenebrutinib), within 4 weeks of screening.
• Cyclophosphamide (oral or intravenous [IV]) within 6 months of Day 1.
• Cytotoxic agents such as chlorambucil, nitrogen mustard or other alkylating agents within 6 months of Day 1.
• Intravenous immunoglobulin, within 12 weeks of Day 1.
• Plasmapheresis or extracorporeal photophoresis, or use of plasma filtering devices within 12 weeks of screening.
• Intra-articular, IM, or IV corticosteroids within 6 weeks of Day 1. Other exclusion criteria (Part D):
• Sensitivity to the clinical study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the clinical study.
• Current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to 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 (whichever is longer) before allocation.
• Use of any medicinal products intended to treat medical conditions that are not approved by the governing health authority in the participant’s country or region.
• Participants who are expected to be non-compliant with restrictions on medications and vaccinations prior to the study, during the study.