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

Phase 3

Recruiting

• Conditions: Lung Diseases, Interstitial
• Interventions: Biological: Belimumab; Other: Placebo

• Registration Number: NCT06572384
• Lead Sponsor: GlaxoSmithKline

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-16
• Study First Submitted QC: 2024-08-22
• Study Start: 2024-08-26
• Study First Posted: 2024-08-27
• Last Update Submitted: 2024-08-28
• Last Update Posted: 2024-08-29
• Primary Completion: 2028-10-18
• Study Completion: 2028-12-13

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 440

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

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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 hospitalisation).
• FVC ≤ 45% of predicted, or a Diffusing Capacity of the lung for Carbon Monoxide (DLco) (corrected for hemoglobin) ≤ 40% of predicted or requiring supplemental oxygen at screening
• History or presence of diffuse alveolar haemorrhage (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 HRCT (extent of emphysema exceeds extent of ILD)
• Confirmed Progressive multifocal leukoencephalopathy (PML) or unexplained new-onset or deteriorating neurologic signs and symptoms
• Have evidence of moderate to severe depression, defined as PHQ-9 score ≥10, or serious current suicide risk, 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Belimumab	Belimumab	Participants will receive belimumab in addition to standard therapy.
Placebo	Placebo	Participants will receive placebo in addition to standard therapy.

Primary Outcome Measures

Name	Time	Method
Absolute Change from Baseline in Forced Vital Capacity (FVC) milliliter (mL) at Week 52	Baseline and Week 52	Forced vital capacity is the total amount of air exhaled during the lung function test. Low FVC (mL) reflects more impaired lung function. Absolute Change from Baseline in FVC will be reported.

Secondary Outcome Measures

Name	Time	Method
Absolute Change from Baseline in FVC Percentage (%) Predicted at Week 52	Baseline and Week 52	FVC are expressed as a percentage of the predicted normal for a person of the same sex, age, and height. Lower % predicted FVC (mL) reflects more impaired lung function.
Absolute Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Week 52	Baseline and Week 52	The FACIT-Fatigue is a short, 13-item questionnaire that assesses self-reported fatigue and its associated impact for daily activities over the past 7 days. The scale range is from 0 to 52, with 0 being the worst possible score and 52 being the best possible score (indicating less/no fatigue).
Absolute Change from Baseline in Quantitative Interstitial Lung Disease in the Whole Lung (QILD-WL) at Week 52	Baseline and Week 52	Change from baseline in extent of architectural distortion (fibrosis), ground glass opacification, and honeycombing features on High-resolution computed tomography (HRCT) as measured by computer-aided analysis tools. Extent of ILD is calculated by summing pixel counts and expressing this as a percentage of the whole lung. ILD extent can range from 0-100% with higher percentage representing more extensive ILD.
Achieving Relative Decline from Baseline in FVC (mL) ≥ 10 % at Week 52	Baseline and Week 52
Time to ILD Progression or Death	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	Time taken for a participant to experience ILD progression or death.
Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score at Week 52	Baseline and Week 52	The L-PF questionnaire is a 49-item questionnaire with two modules: 1) symptoms (28 items) and 2) impacts (21 items). The Symptoms module yields three domain scores: 1) dyspnea, 2) cough and 3) fatigue as well as a total Symptoms score. Participants rate the severity of their symptoms in the last 24 hour on a 5-point rating scale. Scoring is performed as a summary score, the mean of the dimension ratings multiplied by 100. Summary scores range from 0-100, with the higher the score the greater the impairment.
Achieving Relative Decline from Baseline in FVC (mL) ≥ 5% at Week 52	Baseline and Week 52
Absolute Change from Baseline in Living with. Pulmonary Fibrosis (L-PF) Impacts Total Score at Week 52	Baseline and Week 52	The L-PF questionnaire is a 49-item questionnaire with two modules: 1) symptoms (28 items) and 2) impacts (21 items). The Symptoms module yields three domain scores: 1) dyspnea, 2) cough and 3) fatigue as well as a total Symptoms score. Participants rate the severity of their symptoms in the last 24 hour on a 5-point rating scale. Scoring is performed as a summary score, the mean of the dimension ratings multiplied by 100. Summary scores range from 0-100, with the higher the score (100) the greater the impairment.
Absolute Change from Baseline in Quantitative Measures of Lung Fibrosis (QLF) in the Whole Lung at Week 52	Baseline and Week 52	Change from baseline in extent of reticular patterns with architectural distortion (fibrosis) on HRCT as measured by computer-aided analysis tools. Extent of fibrosis is calculated by summing pixel counts and expressing this as a percentage of the whole lung. Fibrosis extent can range from 0-100% with higher percentage representing more extensive fibrosis.
Achieving Greater than or Equal (≥) 2% Decrease in QILD-WL Score at Week 52	Up to Week 52
Cumulative Dose of Corticosteroid over 52 Weeks	Up to Week 52
Absolute Change from Baseline in Kings Brief. Interstitial Lung Disease Questionnaire (K-BILD) at Week 52	Baseline and Week 52	The King's Brief Interstitial Lung Disease (K- ILD) questionnaire consists of 15 items (assessed by the patients on a scale ranging from 1 to 7, where 1 and 7 represent worst and best health status). Items are compiled into 3 domains: breathlessness and activities (range: 0-21), psychological (range: 0-34) , and chest symptoms (range: 0-8). Scores are transformed to a range of 0-100 by using logit values (higher scores indicate better health status). A total score and 3 domain scores are calculated ranging from 0-100 with greater scores (100) denoting better quality of life.
Absolute Change from Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) % Predicted at Week 52	Baseline and Week 52
Number of Participants with Respiratory Related Hospitalizations up to Week 52	Up to Week 52
Time to Connective Tissue Disease Progression	Up to 52 Weeks	Time taken for a participant to experience CTD progression.
Absolute Change from Baseline in Transition Dyspnea Index (TDI) at Week 52	Baseline and Week 52	TDI assess dyspnea severity at baseline and its change over time. TDI includes 3 components: functional impairment, magnitude of task and magnitude of effort. Each component has 7 grades, ranging from -3 (major deterioration) to +3 (major improvement), which are summed to calculate a score, ranging between - 9 and +9. Lower score indicates more severely the participant is affected by dyspnea.
Absolute Change from Baseline in Short Form Health Survey 36-Item Version 2 (SF36-v2) at Week 52	Baseline and Week 52	The SF-36 yields an 8-scale profile of functional health and well-being scores as well as physical and mental component health summary scores. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score (0) the more disability.
Absolute Change from Baseline in Physician Global Assessment (PhGA) at Week 52	Baseline and Week 52	The PhGA is a score which enables the treating physician to rate the participants disease on a scale from 0 to 10, where higher score (10) indicates greater severity.
Absolute Change in Patient Global Impression of Change (PGIC)-ILD at Week 52	Baseline and Week 52	The PGIC contains two items, a global question asking participants to rate their overall change in ILD severity since first starting this study using a 7-point verbal rating scale, and a yes/no question asking participants to indicate whether the change is meaningful from their perspective.
Number of Participants with Adverse Events (AEs), Adverse Events of Special Interest (AESIs) Serious Adverse Events (SAEs)	Up to Week 60

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Sevilla, Spain