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

Phase 3

Recruiting

• Conditions: Lung Diseases
• Interventions: Other: Placebo; Drug: Rituximab

• Registration Number: NCT05596786
• Lead Sponsor: University Hospital, Tours

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-19
• Study First Submitted QC: 2022-10-24
• Study First Posted: 2022-10-27
• Study Start: 2023-01-16
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-22
• Last Update Posted: 2024-07-24
• Primary Completion: 2026-07-16
• Study Completion: 2026-07-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 126

Inclusion Criteria

1. Patients ≥ 18 years old

2. Who meet at least one of the following criteria for worsening ILD within 24 months:

   1. a relative decline in the FVC of >= 10% of the predicted value
   2. 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.
   3. worsening of respiratory symptoms AND an increased extent of ILD on high-resolution CT

3. AND presence of an inflammatory component defined by

   1. 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...)
   2. OR a previous alveolar lymphocytosis >20% on Bronchoalveolar lavage fluid (BALF)

4. Subjects covered by the French social security system

5. Written informed consent obtained from subject

6. Ability for subject to comply with the requirements of the study

Exclusion Criteria

1. 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.
2. 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.
3. Patient who can not walk more than 100 meters at 6-minutes walk test
4. HRCT profile of typical usual interstitial pneumonia (UIP)
5. Histological model of typical NSIP or definitive UIP
6. Initiation of a new therapy or with interruption/modification of therapy dosage within 6 weeks prior to visit 1
7. Patient who has already received a rituximab-based treatment line
8. Known hypersensitivity to rituximab, to murine proteins or other excipients or sulfonamide antibiotics.
9. 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.
10. Patients on a lung transplant list
11. 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.
12. 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.
13. 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)
14. Patient under judicial protection, deprivation of liberty
15. Participation in other interventional research with an investigational drug or medical device.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Rituximab	Rituximab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Forced vital capacity	From baseline to 6 months	Change from baseline to 6 months in FVC (in % of predicted)
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.15 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)
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
Adverse events	From baseline to 6 months	Description of All adverse events, especially serious infectious adverse events, occurring during the six-month treatment period
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.
Severe Acute Respiratory Syndrome COronaVirus 2 (SARS COV 2) antibodies	From baseline to 6 months	Change of SARS COV 2 antibodies
6 minutes walk test	From baseline to 6 months	Changes in the 6-minute walk test
High-resolution computed tomography (HRCT) of chest images	From baseline to 6 months	Changes in high-resolution computed tomography (HRCT) of chest images
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.
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.
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.

Trial Locations

Locations (1)

Chru Tours; 🇫🇷 Tours, France