A Study of the Efficacy and Safety of Belimumab in Adults With Interstitial Lung Disease Associated With Connective Tissue Disease

Interstitial lung disease (ILD) is a lung condition resulting in inflammation and stiffening of the lung, often associated with connective tissue diseases (CTDs). ILD causes reduction in lung volume, shortness of breath, cough and fatigue therefore has high impact on quality of life and is also the leading cause of death in participants with these conditions. The study will assess whether treatment of CTD-ILD participants with belimumab in addition to standard therapy will result in the stabilization and/or improvement of lung function and improve symptoms associated with ILD with an acceptable safety profile.

Inclusion criteria: * Participants with persistent/worsening active inflammatory disease who have failed to achieve their treatment goal, i. e., those who have experience lack of expected treatment benefit (clinically meaningful improvement in FVC), fail to demonstrate sustained lung function stability or continue to experience worsening of ILD despite initiation of standard therapy or failed to tolerate standard therapy. * Documented diagnosis of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), idiopathic inflammatory myopathy (IIM; including polymyositis, dermatomyositis, anti-synthetase syndrome), Sjogren's syndrome (pSS), or mixed connective tissue disease (MCTD) in accordance with internationally recognized classification criteria * Diagnosis of inflammatory and/or fibrotic ILD on High Resolution Computed Tomography (HRCT) with a total disease extent of greater than or equal to (≥) 10% of the whole lung * Evidence of persistent active/worsening ILD * Must be currently receiving stable standard therapy to manage ILD and/or underlying CTD, or to have failed or failed to tolerate standard therapy. * Participant is capable and willing to self-administer the study medication or has a caregiver who is capable and willing to administer the study medication throughout the study * A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: * Is a woman of nonchildbearing potential (WONCBP) OR * Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of less than (\<)1% * Capable of giving signed informed consent Exclusion Criteria: * Diagnosis of ILD other than CTD-ILD. * Primary diagnosis of Systemic Sclerosis (SSc). * Participants with rapidly progressive disease (absolute drop of 10% or more of FVC between screening and baseline visit and/or recent pulmonary hospitalization). * FVC ≤ 45% of predicted, or a Diffusing Capacity of the lung for Carbon Monoxide (DLco) (corrected for hemoglobin) ≤ 40% of predicted at screening as confirmed by central reader * History or presence of diffuse alveolar hemorrhage (DAH) or other confounding pulmonary disease, signs, or symptoms * Pulmonary arterial hypertension requiring therapy, as determined by the investigator at, or prior to first day of dosing (Day 1) * Dependence on continuous oxygen supplementation * History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data * Obstructive pulmonary disease (pre-bronchodilator Forced Expiratory Volume (FEV1) /FVC \<0.7) as confirmed by central reader * Significant emphysema on screening or historical HRCT (extent of emphysema exceeds extent of ILD) as confirmed by central reader * Confirmed Progressive multifocal leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms * Participants with patient health questionnaire (PHQ-9) score ≥10, that in the opinion of a mental healthcare professional pose a serious suicide risk, have or any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months, or who in the investigator's judgment, poses a significant suicide risk. * Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Breast cancer within the past 10 years * Major surgery (including joint surgery) within 3 months prior to screening or planned during the duration of the study * An active infection, or a history of infections