EvER-ILD2: Evaluation of Efficacy and Safety of Rituximab in Patients With Progressive Interstitial Lung Disease (ILD) With Inflammatory Component: a Multicentre Double-blind Placebo-controlled Randomized Trial
Study Details
Study Description
Brief Summary
The main objective of the EvER-ILD2 study is to evaluate the efficacy on lung function at 6 months of one course rituximab (2 infusions) comparatively to one course of placebo (2 infusions) in a broad range of progressive ILD patients with inflammatory component.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rituximab
|
Drug: Rituximab
One course of IV rituximab consisting of a first infusion of 1000 mg (500 mL solution) rituximab (day 1), and a second infusion of 1000 mg (500 mL solution) rituximab two weeks later (day 15)
|
| Placebo Comparator: Placebo
|
Other: Placebo
One course of IV placebo of rituximab consisting of a first infusion of 500 mL of saline (0.9% sodium chloride) infusion (day 1), and a second infusion of 500 mL of saline infusion two weeks later (day 15)
|
Outcome Measures
Primary Outcome Measures
- Forced vital capacity [From baseline to 6 months]
The primary outcome is the change in Forced Vital Capacity (FVC) (in mL) from baseline to 6 months.
Secondary Outcome Measures
- Forced vital capacity [From baseline to 6 months]
Change from baseline to 6 months in FVC (in % of predicted)
- Progression free survival (PFS) [At 6 months]
Progression free survival (PFS) defined as the time to (first event considered): a first acute exacerbation, or a relative decline in the FVC of ≥ 10% of the predicted value or the need for new immunosuppressive or/and anti-fibrotic therapies (excluding corticosteroids), or inclusion on a lung transplant list, or death.
- King's Brief Interstitial Lung Disease (K-BILD) questionnaire [From baseline to 6 months]
Changes in the King's Brief Interstitial Lung Disease (K-BILD) questionnaire.13 questions about the impact of lung disease on life.
- L-PF symptom questionnaire [From baseline to 6 months]
Changes in "Living Pulmonary fibrosis-symptom" questionnaire.23 questions about the impact of lung disease on life.
- L-PF impact questionnaire [From baseline to 6 months]
Changes in "Living Pulmonary fibrosis-impact" questionnaire.21 questions about the impact of lung disease on life.
- Cumulative doses of corticosteroids [At 6 months]
Difference in cumulative doses of corticosteroids
- Diffusing capacity for carbon monoxide (DLCO) [From baseline to 6 months]
Changes in % of predicted diffusing capacity for carbon monoxide (DLCO)
- 6 minutes walk test [From baseline to 6 months]
Changes in the 6-minute walk test
- Accelerometer-assessed physical activity [From baseline to 6 months]
Change in accelerometer-assessed physical activity
- Biological analyse on markers related to B-cell depletion [From baseline to 6 months]
Changes of biological markers related to B-cell depletion
- Environmental antigens [From baseline to 6 months]
Changes of serology by ELISA of 15 environmental antigens.
- High-resolution computed tomography (HRCT) of chest images [From baseline to 6 months]
Changes in high-resolution computed tomography (HRCT) of chest images
- Adverse events [From baseline to 6 months]
Description of All adverse events, especially serious infectious adverse events, occurring during the six-month treatment period
- Pharmacokinetic parameters of rituximab [before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion]
Rituximab clearance
- Pharmacokinetic parameters of rituximab [Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion]
Volume of distribution
- Pharmacokinetic parameters of rituximab [Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion]
Half life
- Severe Acute Respiratory Syndrome COronaVirus 2 (SARS COV 2) antibodies [From baseline to 6 months]
Change of SARS COV 2 antibodies
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients ≥ 18 years old
-
Who meet at least one of the following criteria for worsening ILD within 24 months:
-
a relative decline in the FVC of >= 10% of the predicted value
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a relative decrease in the FVC of >=5 to 10% of the predicted value AND i) worsening respiratory symptoms OR ii) an increased extent of ILD on high-resolution CT OR iii) a relative decrease in the DLCO of >= 15% of the predicted value.
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worsening of respiratory symptoms AND an increased extent of ILD on high-resolution CT
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AND presence of an inflammatory component defined by
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a previous histological pattern with lymphocyte infiltrations distant from pulmonary fibrosis to suggest an inflammatory component on pulmonary sample (for example: interstitial lymphoid aggregates with germinal centers, diffuse lympho-plasmocytic infiltrations, granulomas, giant cells or centrilobular inflammation…)
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OR a previous alveolar lymphocytosis >20% on Bronchoalveolar lavage fluid (BALF)
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Subjects covered by the French social security system
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Written informed consent obtained from subject
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Ability for subject to comply with the requirements of the study
Exclusion Criteria:
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Known diagnosis of significant respiratory disorders (asthma, tuberculosis, aspergillosis, cystic fibrosis, idiopathic pulmonary fibrosis (IPF), Connective Tissue Diseases-ILD, sarcoidosis, desquamative interstitial pneumonia, pulmonary hypertension (PAMp > 30mmHg))) or of significant severe heart failure.
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Concomitant medical or surgical disease, clinically significant as considered by the investigator, serious or unstable, acute or chronically progressive, or any condition that could affect the safety of the patient, in the opinion of the investigator including cardiomyopathy or heart failure.
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Patient who can not walk more than 100 meters at 6-minutes walk test
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HRCT profile of typical usual interstitial pneumonia (UIP)
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Histological model of typical NSIP or definitive UIP
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Initiation of a new therapy or with interruption/modification of therapy dosage within 6 weeks prior to visit 1
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Patient who has already received a rituximab-based treatment line
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Known hypersensitivity to rituximab, to murine proteins or other excipients or sulfonamide antibiotics.
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Treatment with monoclonal antibodies (such as, but not limited to, etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab) within 6 months (if 5 half-lives ≤ 6 months) prior to inclusion.
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Patients on a lung transplant list
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Pregnant or breastfeeding women, or women of childbearing age not using a reliable method of contraception during the study and for 12 months following the end of the study treatment.
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Patients at high risk of infectious complications: Human Immunodeficiency Virus (HIV) positive or other known immunodeficiency syndromes, hepatitis B and C (HBV, HCV), coronavirus disease (within 3 month) or other known viral infection, infection requiring anti-infective treatment within 4 weeks of inclusion.
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Patients with incomplete anti-severe acute respiratory syndrome coronavirus 2 vaccine regimen (according to current recommendations) and in this case who has not receive a treatment with therapeutic antibodies anti-SARSCov2 (ex: tixagévimab/cilgavimab)
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Patient under judicial protection, deprivation of liberty
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Participation in other interventional research with an investigational drug or medical device.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University Hospital, Tours
Investigators
- Study Director: Julien LE BONNIEC, University Hospital Center of Tours
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DR210299