Clinical trial NCT06572384: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Diseases, Interstitial
Keywords: Interstitial lung disease
Belimumab
Connective Tissue Disease
Autoimmune disease
Lung Diseases
Interstitial
Safety
Efficacy
Monoclonal antibody
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-08-27
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a two-group parallel study.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion criteria:

* 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 ILD on High Resolution Computed Tomography (HRCT) with disease extent of greater than or equal to (≥) 10% of the whole lung (WLILD)
* Evidence of ILD progression in the previous 24 months
* Must be currently receiving stable standard therapy to manage ILD and/or underlying CTD, or to have failed or failed to tolerate first line 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
* 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).
* Significant emphysema on screening or historical HRCT (extent of emphysema exceeds extent of ILD)
* 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, or have 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

Primary outcomes:
measure: Absolute Change from Baseline in Forced Vital Capacity (FVC) milliliter (mL) at Week 52
timeFrame: Baseline and Week 52
Secondary outcomes:
measure: Absolute Change from Baseline in FVC Percentage (%) Predicted at Week 52
timeFrame: Baseline and Week 52
measure: Time to ILD Progression or Death
timeFrame: 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
measure: Absolute Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Quantitative Interstitial Lung Disease in the Whole Lung (QILD-WL) At Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Quantitative Measures of Lung Fibrosis (QLF) in the Whole Lung At Week 52
timeFrame: Baseline and Week 52
measure: Achieving Greater than or Equal (≥) 2% Decrease in QILD-WL Score at Week 52
timeFrame: Up to Week 52
measure: Achieving Relative Decline from Baseline in FVC (mL) ≥ 5% at Week 52
timeFrame: Baseline and Week 52
measure: Achieving Relative Decline from Baseline in FVC (mL) ≥ 10% at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Steroid Dose (Prednisone Equivalent Dose) at Week 52
timeFrame: Baseline and Week 52
measure: Time to Connective Tissue Disease Progression
timeFrame: Up to 52 Weeks
measure: Absolute Change from Baseline in Transition Dyspnea Index (TDI) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Short Form Health Survey 36-Item Version 2 (SF36-v2) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Impacts Total Score at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Kings Brief Interstitial Lung Disease Questionnaire (K-BILD) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Physician Global Assessment (PhGA) at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change in Patient Global Impression of Change (PGIC)-ILD at Week 52
timeFrame: Baseline and Week 52
measure: Absolute Change from Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) % Predicted at Week 52
timeFrame: Baseline and Week 52
measure: Number of Participants with Adverse Events (AEs), Adverse Events of Special Interest (AESIs) Serious Adverse Events (SAEs)
timeFrame: Up to Week 60
measure: Number of Participants with Respiratory Related Hospitalizations up to Week 52
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Upland
country: United States
facility: GSK Investigational Site
state: California
city: Gainesville
country: United States
facility: GSK Investigational Site
state: Florida
city: Naples
country: United States
facility: GSK Investigational Site
state: Florida
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Potsdam
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Temple
country: United States
facility: GSK Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Cordoba
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: San Miguel de TucumAn
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Adelaide
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Woodville
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Spearwood
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Namur
country: Belgium
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Sao Jose Do Rio Preto
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Trois RiviEres
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Chengdu
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Hangzhou
country: China
facility: GSK Investigational Site
city: Mianyang
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Nanning
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Suzhou
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: ZhuZhou
country: China
facility: GSK Investigational Site
city: Angers Cedex 9
country: France
facility: GSK Investigational Site
city: Le Kremlin-bicetre
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Pessac cedex
country: France
facility: GSK Investigational Site
city: Rouen Cedex
country: France
facility: GSK Investigational Site
city: Toulouse cedex 9
country: France
facility: GSK Investigational Site
city: Essen
country: Germany
facility: GSK Investigational Site
city: Minden
country: Germany
facility: GSK Investigational Site
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: Ancona
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Pavia
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Udine
country: Italy
facility: GSK Investigational Site
city: Verona
country: Italy
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Miyazaki
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tottori
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
city: Bucheon Kyunggi-Do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Yongsan-Ku Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Chihuahua
country: Mexico
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Ciudad de Panama
country: Panama
facility: GSK Investigational Site
city: Panama City
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: COrdoba
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Pamplona
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: