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

Официальное название

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)

Обзор

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.

Вмешательства

• Биопрепарат Belimumab
  Belimumab will be administered.
• Другое Placebo
  Placebo will be administered.

Первичные конечные точки

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

Вторичные конечные точки (12)

• Absolute Change from Baseline in FVC Percentage (%) Predicted at Week 52 [Срок оценки: Baseline and Week 52]
• Time to ILD Progression or Death [Срок оценки: 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 [Срок оценки: Baseline and Week 52]
• Absolute Change from Baseline in Living with Pulmonary Fibrosis (L-PF) Total Symptom Score at Week 52 [Срок оценки: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Interstitial Lung Disease in the Whole Lung (QILD-WL) At Week 52 [Срок оценки: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Measures of Lung Fibrosis (QLF) in the Whole Lung At Week 52 [Срок оценки: Baseline and Week 52]
• Absolute Change from Baseline in Quantitative Ground Glass Opacity in the Whole Lung (QGGO-WL) at Week 52 [Срок оценки: Baseline and Week 52]
• Achieving Relative Decline from Baseline in FVC (mL) ≥ 5% at Week 52 [Срок оценки: Baseline and Week 52]
• Achieving Relative Decline from Baseline in FVC (mL) ≥ 10% at Week 52 [Срок оценки: Baseline and Week 52]
• Absolute Change from Baseline in Steroid Dose (Prednisone Equivalent Dose) at Week 52 [Срок оценки: Baseline and Week 52]
• Time to Connective Tissue Disease Progression [Срок оценки: Up to 52 Weeks]
• Absolute Change from Baseline in Transition Dyspnea Index (TDI) at Week 52 [Срок оценки: Baseline and Week 52]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 17 центров

• GSK Investigational Site — Пекин
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• GSK Investigational Site — Чэнду
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• GSK Investigational Site — Ханчжоу
• GSK Investigational Site — Mianyang
• … и ещё 9 центров

США · 16 центров

• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
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• GSK Investigational Site — San Francisco
• GSK Investigational Site — Upland
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Япония · 14 центров

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Италия · 12 центров

• GSK Investigational Site — Ancona
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Испания · 10 центров

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Аргентина · 9 центров

• GSK Investigational Site — Buenos Aires
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• GSK Investigational Site — Ciudad Autonoma Buenos Aires
• GSK Investigational Site — Córdoba
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• … и ещё 1 центр

Бразилия · 7 центров

• GSK Investigational Site — Barra Mansa
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Франция · 6 центров

• GSK Investigational Site — Angers
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• GSK Investigational Site — Lille
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Мексика · 6 центров

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South Korea · 6 центров

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Panama · 5 центров

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Бельгия · 4 центра

• GSK Investigational Site — Brussels
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Германия · 4 центра

• GSK Investigational Site — Essen
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Греция · 4 центра

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

Австралия · 3 центра

• GSK Investigational Site — Adelaide
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Нидерланды · 3 центра

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Великобритания · 3 центра

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Канада · 2 центра

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

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗