A Study of the Efficacy and Safety of Belimumab in Adults With Interstitial Lung Disease Associated With Connective Tissue Disease
NCT Number: NCT06572384
Acronym: BEconneCTD-ILD
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Lung Diseases, Interstitial
Interventions: BIOLOGICAL: Belimumab|OTHER: Placebo
Sponsor: GlaxoSmithKline
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 440
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-26
Completion Date: 2028-12-13
Locations: GSK Investigational Site, Los Angeles, California, 90033, United States|GSK Investigational Site, Los Angeles, California, 90095, United States|GSK Investigational Site, Los Angeles, California, 92868, United States|GSK Investigational Site, San Francisco, California, 94143, United States|GSK Investigational Site, Upland, California, 91786, United States|GSK Investigational Site, Gainesville, Florida, 32608, United States|GSK Investigational Site, Naples, Florida, 34102, United States|GSK Investigational Site, Bay Saint Louis, Mississippi, 63110, United States|GSK Investigational Site, New York, New York, 10029, United States|GSK Investigational Site, New York, New York, 10032, United States|GSK Investigational Site, Potsdam, New York, 13676, United States|GSK Investigational Site, Durham, North Carolina, 27710, United States|GSK Investigational Site, Philadelphia, Pennsylvania, 19140, United States|GSK Investigational Site, Houston, Texas, 77030, United States|GSK Investigational Site, Temple, Texas, 76508, United States|GSK Investigational Site, Salt Lake City, Utah, 84108, United States|GSK Investigational Site, Buenos Aires, 1023, Argentina|GSK Investigational Site, Buenos Aires, C1425AGC, Argentina|GSK Investigational Site, Ciudad Autonoma de Buenos Aires, C1128AAF, Argentina|GSK Investigational Site, Cordoba, X5000AAW, Argentina|GSK Investigational Site, Mendoza, 5500, Argentina|GSK Investigational Site, Rosario, S2002, Argentina|GSK Investigational Site, San Miguel de TucumAn, T4000, Argentina|GSK Investigational Site, Adelaide, 5000, Australia|GSK Investigational Site, Murdoch, 6163, Australia|GSK Investigational Site, Woodville, 5011, Australia|GSK Investigational Site, Bruxelles, 1200, Belgium|GSK Investigational Site, LiEge, 4000, Belgium|GSK Investigational Site, Namur, 5000, Belgium|GSK Investigational Site, Barra Mansa, 27323240, Brazil|GSK Investigational Site, Juiz de Fora, 36010-570, Brazil|GSK Investigational Site, Porto Alegre, 90020-090, Brazil|GSK Investigational Site, Porto Alegre, 90480000, Brazil|GSK Investigational Site, Sao Jose do Rio Preto, 15090-000, Brazil|GSK Investigational Site, SAo Paulo, 04004-030, Brazil|GSK Investigational Site, Sao Paulo, 05403-900, Brazil|GSK Investigational Site, Montreal, H3T 1E2, Canada|GSK Investigational Site, Trois RiviEres, G9A 4P3, Canada|GSK Investigational Site, Beijing, 100020, China|GSK Investigational Site, Beijing, 100730, China|GSK Investigational Site, Chengdu, 610072, China|GSK Investigational Site, Guangzhou, 510100, China|GSK Investigational Site, Guangzhou, 510630, China|GSK Investigational Site, Hangzhou, 310003, China|GSK Investigational Site, Hangzhou, 310052, China|GSK Investigational Site, Mianyang, China|GSK Investigational Site, Nanjing, 210008, China|GSK Investigational Site, Nanjing, 210029, China|GSK Investigational Site, Nanning, 530000, China|GSK Investigational Site, Shanghai, 200001, China|GSK Investigational Site, Shanghai, 200040, China|GSK Investigational Site, Shenyang, 110001, China|GSK Investigational Site, Suzhou, China|GSK Investigational Site, Tianjin, 300052, China|GSK Investigational Site, ZhuZhou, 412007, China|GSK Investigational Site, Angers Cedex 9, 49933, France|GSK Investigational Site, Le Kremlin-BicEtre, 94275, France|GSK Investigational Site, Lille, 59037, France|GSK Investigational Site, Pessac cedex, 33604, France|GSK Investigational Site, Rouen Cedex, 76000, France|GSK Investigational Site, Toulouse cedex 9, 31059, France|GSK Investigational Site, Essen, 45293, Germany|GSK Investigational Site, Mainz, 55131, Germany|GSK Investigational Site, Minden, 32429, Germany|GSK Investigational Site, Sendenhorst, 48324, Germany|GSK Investigational Site, Wuerzburg, 97080, Germany|GSK Investigational Site, Athens, 106 76, Greece|GSK Investigational Site, Athens, 124 62, Greece|GSK Investigational Site, Athens, 12462, Greece|GSK Investigational Site, Larissa, 41110, Greece|GSK Investigational Site, Ancona, Italy|GSK Investigational Site, Milano, 20132, Italy|GSK Investigational Site, Milano, Italy|GSK Investigational Site, Modena, 41124, Italy|GSK Investigational Site, Napoli, 80131, Italy|GSK Investigational Site, Padova, Italy|GSK Investigational Site, Pavia, 27100, Italy|GSK Investigational Site, Pisa, 56126, Italy|GSK Investigational Site, Roma, 00128, Italy|GSK Investigational Site, Roma, Italy|GSK Investigational Site, Udine, 33100, Italy|GSK Investigational Site, Verona, 37134, Italy|GSK Investigational Site, Aichi, 470-1192, Japan|GSK Investigational Site, Fukuoka, 807-8556, Japan|GSK Investigational Site, Fukuoka, 812-8582, Japan|GSK Investigational Site, Hiroshima, 734-8551, Japan|GSK Investigational Site, Hokkaido, 060-8648, Japan|GSK Investigational Site, Kanagawa, 216-8511, Japan|GSK Investigational Site, Miyagi, 983-8512, Japan|GSK Investigational Site, Miyazaki, 889-1692, Japan|GSK Investigational Site, Saitama, 350-0495, Japan|GSK Investigational Site, Tokyo, 113-8519, Japan|GSK Investigational Site, Tokyo, 113-8603, Japan|GSK Investigational Site, Tokyo, 143-8541, Japan|GSK Investigational Site, Tottori, 683-8504, Japan|GSK Investigational Site, Yamanashi, 409-3898, Japan|GSK Investigational Site, Bucheon Kyunggi-Do, 420-717, Korea, Republic of|GSK Investigational Site, Seoul, 05505, Korea, Republic of|GSK Investigational Site, Seoul, 06351, Korea, Republic of|GSK Investigational Site, Seoul, 06591, Korea, Republic of|GSK Investigational Site, Suwon Kyunggi-do, 443-721, Korea, Republic of|GSK Investigational Site, Yongsan-Ku Seoul, Korea, Republic of|GSK Investigational Site, Chihuahua, 31000, Mexico|GSK Investigational Site, Ciudad de Mexico, 03310, Mexico|GSK Investigational Site, DF, 14080, Mexico|GSK Investigational Site, Guadalajara, 44650, Mexico|GSK Investigational Site, Merida, CP 97070, Mexico|GSK Investigational Site, Mexico, 14080, Mexico|GSK Investigational Site, Monterrey, 64460, Mexico|GSK Investigational Site, Maastricht, 6229 HX, Netherlands|GSK Investigational Site, Rotterdam, 3015 GD, Netherlands|GSK Investigational Site, Utrecht, 3584 CX, Netherlands|GSK Investigational Site, Ciudad de Panama, 7099, Panama|GSK Investigational Site, Panama City, Panama|GSK Investigational Site, Panama, 07126, Panama|GSK Investigational Site, Panama, 7002, Panama|GSK Investigational Site, Panama, Panama|GSK Investigational Site, Barcelona, 08025, Spain|GSK Investigational Site, Barcelona, ?08035, Spain|GSK Investigational Site, COrdoba, 14004, Spain|GSK Investigational Site, Granada, 18016, Spain|GSK Investigational Site, Madrid, 28007, Spain|GSK Investigational Site, Madrid, 28046, Spain|GSK Investigational Site, Malaga, 29530, Spain|GSK Investigational Site, Pamplona, 31008, Spain|GSK Investigational Site, Santander, 39011, Spain|GSK Investigational Site, Sevilla, 41013, Spain

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.

Primary Outcome Measures: Absolute Change from Baseline in Forced Vital Capacity (FVC) milliliter (mL) at 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., Baseline and Week 52
Secondary Outcome Measures: Absolute Change from Baseline in FVC Percentage (%) Predicted at 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., Baseline and Week 52|Time to ILD Progression or Death, Time taken for a participant to experience 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|Absolute Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at 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)., Baseline and Week 52|Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score at 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., Baseline and Week 52|Absolute Change from Baseline in Quantitative Interstitial Lung Disease in the Whole Lung (QILD-WL) at 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., Baseline and Week 52|Absolute Change from Baseline in Quantitative Measures of Lung Fibrosis (QLF) in the Whole Lung at 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., Baseline and Week 52|Achieving Greater than or Equal (≥) 2% Decrease in QILD-WL Score at Week 52, Up to Week 52|Achieving Relative Decline from Baseline in FVC (mL) ≥ 5% at Week 52, Baseline and Week 52|Achieving Relative Decline from Baseline in FVC (mL) ≥ 10 % at Week 52, Baseline and Week 52|Cumulative Dose of Corticosteroid over 52 Weeks, Up to Week 52|Time to Connective Tissue Disease Progression, Time taken for a participant to experience CTD progression., Up to 52 Weeks|Absolute Change from Baseline in Transition Dyspnea Index (TDI) at 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., Baseline and Week 52|Absolute Change from Baseline in Short Form Health Survey 36-Item Version 2 (SF36-v2) at 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., Baseline and Week 52|Absolute Change from Baseline in Living with. Pulmonary Fibrosis (L-PF) Impacts Total Score at 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., Baseline and Week 52|Absolute Change from Baseline in Kings Brief. Interstitial Lung Disease Questionnaire (K-BILD) at 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., Baseline and Week 52|Absolute Change from Baseline in Physician Global Assessment (PhGA) at 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., Baseline and Week 52|Absolute Change in Patient Global Impression of Change (PGIC)-ILD at 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., Baseline and Week 52|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 Adverse Events (AEs), Adverse Events of Special Interest (AESIs) Serious Adverse Events (SAEs), Up to Week 60|Number of Participants with Respiratory Related Hospitalizations up to Week 52, Up to Week 52