The purpose of the study is to evaluate the efficacy on lung function 6 months after one course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one course of placebo and 6 months of MMF treatment in a broad range of patients with Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
122
Rituximab 500mg concentrate for solution for infusion. One course of IV rituximab consisting of a first infusion of 1000 mg (500 ml solution) rituximab (day 1 infusion), and a second infusion of 1000 mg (500 ml solution) rituximab two weeks later (day 15 infusion)
500 ml of saline (0.9% sodium chloride) for infusion One course of intravenous placebo of rituximab consisting of a first infusion of 500 ml of saline (0.9% sodium chloride) infusion (day 1 infusion), and a second infusion of 500 ml of saline infusion two weeks later (day 15 infusion)
Mycophenolate Mofetil 500mg film-coated tablets 1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.
Chu Besancon
Besançon, France
Chu Dijon
Dijon, France
AP-HM Hôpital NORD
Marseille, France
Chu Rennes
Rennes, France
CHRU Tours
Tours, France
Change in FVC in % of predicted
Change in FVC (in % of predicted) since declines in FVC correlates with increased risk of subsequent mortality in ILD patients and FVC is one of the core set of outcomes defined in interstitial lung diseases. Data obtained from the two groups of patients (rituximab and placebo) will be compared to each other. FVC will be performed in each study center in a standardized manner according to the ATS/ERS recommendations and ECCS reference equations
Time frame: From baseline to 6 months
Progression Free Survival (PFS).
PFS is defined as the time 1) to the first acute exacerbation, or 2) to an absolute decline of 10 % points in the percentage of the predicted FVC, or 3) to the necessity to withdraw the MMF with/without a new immunosuppressive treatment (except corticoids), or 4) to death or 5) registration to a lung transplantation list. An acute exacerbation is defined by (1) progressive dyspnea over 1 month or less; (2) new pulmonary infiltrates on chest radiography or computed tomography, and (3) the absence of an overt underlying cause of rapid deterioration
Time frame: PFS measured at 3, 6 and 12 months
Changes in the quality of life score
The quality of life score as measured by the SF-36 v1.3 questionnaire, version developed and validated in interstitial lung disease (ILD) patients.
Time frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough
Changes in the visual analogic scales of dyspnea
Changes in the visual analogic scales of dyspnea (EVA test)
Time frame: Changes from baseline to 6 months in the quality of life score, and, changes from baseline to 6 months in the visual analogic scales of dyspnea and cough
Cough evaluation
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Changes in cough evaluation
Time frame: Changes from baseline to 6 months in cough evaluation
Cumulative doses of corticoids for the 2 groups
Cumulative doses of corticoids for the 2 groups
Time frame: Cumulative doses of corticoids at 6 months
Changes in the FVC expressed as % of predicted
Changes in the FVC expressed as % of predicted
Time frame: Changes from baseline to 3 and 6 months in the FVC expressed as % of predicted
Changes in DLCO
Changes in DLCO
Time frame: Changes from baseline to 6 months in DLCO
Changes in the 6-minutes-walk test
Changes in the 6-minutes-walk test
Time frame: Changes from baseline to 6 months in the 6-minutes-walk test
Changes in autoantibodies concentration
Changes in autoantibodies concentration
Time frame: Changes from baseline to 6 months in autoantibodies concentration
Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes
Changes in biological markers related to lymphocyte B depletion: CD19 lymphocytes
Time frame: Changes from baseline to 6 months in lymphocytes B CD19
Changes in gammaglobulins
Changes in gammaglobulins
Time frame: Changes from baseline to 6 months in gammaglobulins
Changes in HRCT of the chest images
Changes in HRCT of the chest images
Time frame: Changes from baseline to 6 months in HRCT of the chest images
Adverse events related to treatment
In particular infectious adverse events and biological blood disorders during the 6 months of study period will be collected
Time frame: Adverse events during the 6 months of study period
Rituximab PK parameters : distribution volume
Rituximab PK parameters : distribution volume
Time frame: Points at Day1, Day15, 3 and 6 months
Rituximab clearance
Rituximab clearance
Time frame: Points at Day1, Day15, 3 and 6 months
Half-life of rituximab in blood
Half-life of rituximab in blood
Time frame: Points at Day1, Day15, 3 and 6 months