Evaluating Rituximab for Lung Disease with Inflammation

Evaluation de l'efficacité et de la sécurité du Rituximab Chez Les Patients Avec Une Pneumopathie Interstitielle Diffuse Progressive Avec Composante Inflammatoire : Essai Clinique randomisé Multicentrique en Double Insu Contre Placebo

This study is testing if the drug rituximab can help improve lung function in people with worsening interstitial lung disease that has inflammation.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 126 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: University Hospital, Tours (Academic / other)
• Drugs / interventions: rituximab, adalimumab, efalizumab, infliximab, golimumab, certolizumab, cilgavimab
• Locations: 1 site (Tours)
• Trial ID: NCT05596786 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness and safety of rituximab in improving lung function in patients with progressive interstitial lung disease (ILD) that has an inflammatory component. Participants will receive either rituximab or a placebo in a double-blind manner, with the primary outcome measured at six months. The study focuses on patients who have experienced worsening ILD symptoms and have specific inflammatory markers in their lung tissue. By comparing the effects of the treatment against a placebo, the trial seeks to determine the potential benefits of rituximab for this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with worsening ILD symptoms and evidence of an inflammatory component in their lung condition.

Not a fit: Patients without an inflammatory component in their ILD or those who have not experienced recent worsening of their condition may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung function and quality of life for patients with progressive ILD.

How similar studies have performed: Other studies have explored the use of rituximab in various inflammatory conditions, showing promising results, but this specific application in ILD is relatively novel.

Eligibility criteria

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.

Where this trial is running

Tours

• Chru Tours — Tours, France (Recruiting)

Study contacts

• Study coordinator: Sylvain MARCHAND ADAM, PhD

Conditions Lung Diseases