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

Official title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Belimumab Administered Subcutaneously in Adults With Interstitial Lung Disease (ILD) Associated With Connective Tissue Disease (CTD)

Overview

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.

Interventions

• Biological Belimumab
  Belimumab will be administered.
• Other Placebo
  Placebo will be administered.

Primary outcome measures

• Absolute Change from Baseline in Forced Vital Capacity (FVC) milliliter (mL) at Week 52 [Time frame: Baseline and Week 52]

Secondary outcome measures (12)

• Absolute Change from Baseline in FVC Percentage (%) Predicted at Week 52 [Time frame: Baseline and Week 52]
• Time to ILD Progression or Death [Time frame: From the date of assignment (Day 1) until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 52 Weeks]
• Absolute Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 52 [Time frame: Baseline and Week 52]
• Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score at Week 52 [Time frame: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Interstitial Lung Disease in the Whole Lung (QILD-WL) At Week 52 [Time frame: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Measures of Lung Fibrosis (QLF) in the Whole Lung At Week 52 [Time frame: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Ground Glass Opacity in the Whole Lung (QGGO-WL) at Week 52 [Time frame: Baseline and Week 52]
• Achieving Relative Decline from Baseline in FVC (mL) ≥ 5% at Week 52 [Time frame: Baseline and Week 52]
• Achieving Relative Decline from Baseline in FVC (mL) ≥ 10% at Week 52 [Time frame: Baseline and Week 52]
• Absolute Change from Baseline in Steroid Dose (Prednisone Equivalent Dose) at Week 52 [Time frame: Baseline and Week 52]
• Time to Connective Tissue Disease Progression [Time frame: Up to 52 Weeks]
• Absolute Change from Baseline in Transition Dyspnea Index (TDI) at Week 52 [Time frame: Baseline and Week 52]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 17 centers

• GSK Investigational Site — Beijing
• GSK Investigational Site — Beijing
• GSK Investigational Site — Chengdu
• GSK Investigational Site — Guangzhou
• GSK Investigational Site — Guangzhou
• GSK Investigational Site — Hangzhou
• GSK Investigational Site — Hangzhou
• GSK Investigational Site — Mianyang
• … and 9 more centers

United States · 16 centers

• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — San Francisco
• GSK Investigational Site — Upland
• GSK Investigational Site — Gainesville
• GSK Investigational Site — Naples
• GSK Investigational Site — St Louis
• … and 8 more centers

Japan · 14 centers

Center list to be confirmed — check the primary protocol.

Italy · 12 centers

• GSK Investigational Site — Ancona
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Modena
• GSK Investigational Site — Naples
• GSK Investigational Site — Padova
• GSK Investigational Site — Pavia
• GSK Investigational Site — Pisa
• … and 4 more centers

Spain · 10 centers

Center list to be confirmed — check the primary protocol.

Argentina · 9 centers

• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Ciudad Autonoma Buenos Aires
• GSK Investigational Site — Córdoba
• GSK Investigational Site — Mendoza
• GSK Investigational Site — Rosario
• GSK Investigational Site — San Miguel de Tucumán
• … and 1 more center

Brazil · 7 centers

• GSK Investigational Site — Barra Mansa
• GSK Investigational Site — Juiz de Fora
• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — Porto Alegre
• GSK Investigational Site — São José do Rio Preto
• GSK Investigational Site — São Paulo
• GSK Investigational Site — São Paulo

France · 6 centers

• GSK Investigational Site — Angers
• GSK Investigational Site — Le Kremlin-Bicêtre
• GSK Investigational Site — Lille
• GSK Investigational Site — Pessac
• GSK Investigational Site — Rouen
• GSK Investigational Site — Toulouse

Mexico · 6 centers

Center list to be confirmed — check the primary protocol.

South Korea · 6 centers

Center list to be confirmed — check the primary protocol.

Panama · 5 centers

Center list to be confirmed — check the primary protocol.

Belgium · 4 centers

• GSK Investigational Site — Brussels
• GSK Investigational Site — Brussels
• GSK Investigational Site — Liège
• GSK Investigational Site — Namur

Germany · 4 centers

• GSK Investigational Site — Essen
• GSK Investigational Site — Mainz
• GSK Investigational Site — Minden
• GSK Investigational Site — Würzburg

Greece · 4 centers

• GSK Investigational Site — Athens
• GSK Investigational Site — Athens
• GSK Investigational Site — Athens
• GSK Investigational Site — Larissa

Australia · 3 centers

• GSK Investigational Site — Adelaide
• GSK Investigational Site — Woodville
• GSK Investigational Site — Spearwood

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 3 centers

Center list to be confirmed — check the primary protocol.

Canada · 2 centers

• GSK Investigational Site — Montreal
• GSK Investigational Site — Trois-Rivières

Identifiers

NCT: NCT06572384 · 221672 · 2024-513018-36-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗