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

NCT05596786 | Recruiting Phase 3

• 1 other identifier: DR210299
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Diseases

Outcome Measures

Primary Outcomes (1)

• Forced vital capacity

  The primary outcome is the change in Forced Vital Capacity (FVC) (in mL) from baseline to 6 months.

  From baseline to 6 months

Secondary Outcomes (17)

• Forced vital capacity

  From baseline to 6 months

• Progression free survival (PFS)

  At 6 months

• King's Brief Interstitial Lung Disease (K-BILD) questionnaire

  From baseline to 6 months

• L-PF symptom questionnaire

  From baseline to 6 months

• L-PF impact questionnaire

  From baseline to 6 months

Study Arms (2)

Rituximab

EXPERIMENTAL

Drug: Rituximab

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Rituximab DRUG

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)

Rituximab

Placebo OTHER

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)

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• worsening of respiratory symptoms AND an increased extent of ILD on high-resolution CT
• AND presence of an inflammatory component defined by
• 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…)
• OR a previous alveolar lymphocytosis \>20% on Bronchoalveolar lavage fluid (BALF)
• Subjects covered by the French social security system
• Written informed consent obtained from subject
• Ability for subject to comply with the requirements of the study

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

Chru Tours

Tours, France

RECRUITING

Related Publications (1)

• Ferreira M, Bejan-Angoulvant T, Marchand-Adam S, Mousset E, Mureau E, Jouneau S, Nunes H, Montani D, Chenivesse C, Cadranel J, Bonniaud P, Crestani B, Cottin V, Caille A; OrphaLung.. Evaluation of efficacy and safety of rituximab in patients with progressive interstitial lung disease (ILD) with inflammatory component (EvER-ILD2): A multicentre double-blind placebo-controlled randomized trial. Respir Med Res. 2025 May;87:101144. doi: 10.1016/j.resmer.2024.101144. Epub 2024 Nov 28.

  PMID: 39693827 DERIVED

MeSH Terms

Conditions

Lung Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Julien LE BONNIEC

  University Hospital Center of Tours

  STUDY DIRECTOR

Central Study Contacts

Sylvain MARCHAND ADAM, PhD

CONTACT

+33 2 47 47 98 34; sylvain.marchand-adam@univ-tours.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: October 27, 2022
• Study Start: January 16, 2023
• Primary Completion (Estimated): July 16, 2026
• Study Completion (Estimated): July 16, 2026
• Last Updated: July 24, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)