Lung DiseasesPhase 3EvER-ILD2NCT05596786
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
A Phase 3 study testing Rituximab in people with Lung Diseases, run by University Hospital, Tours at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Lung Diseases
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 126 participants
- Where
- 1 siteFrance
- Study dates
- 16 Jan 2023to 16 Jul 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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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…)
- 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
Who cannot join
- 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
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- Patient who has already received a rituximab-based treatment line
- Known hypersensitivity to rituximab, to murine proteins or other excipients or sulfonamide antibiotics.
- 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.
- 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 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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
- Being tested
- Rituximab, Placebo
- Medical subject headings
- Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
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)
PlaceboOther
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)
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Not described Receives: Drug: Rituximab |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced vital capacity
The primary outcome is the change in Forced Vital Capacity (FVC) (in mL) from baseline to 6 months.
Measured: From baseline to 6 months
Secondary outcomes (17)
Forced vital capacity
Change from baseline to 6 months in FVC (in % of predicted)
Measured: From baseline to 6 months
Progression free survival (PFS)
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.
Measured: At 6 months
King's Brief Interstitial Lung Disease (K-BILD) questionnaire
Changes in the King's Brief Interstitial Lung Disease (K-BILD) questionnaire.15 questions about the impact of lung disease on life.
Measured: From baseline to 6 months
L-PF symptom questionnaire
Changes in "Living Pulmonary fibrosis-symptom" questionnaire.23 questions about the impact of lung disease on life.
Measured: From baseline to 6 months
L-PF impact questionnaire
Changes in "Living Pulmonary fibrosis-impact" questionnaire.21 questions about the impact of lung disease on life.
Measured: From baseline to 6 months
Cumulative doses of corticosteroids
Difference in cumulative doses of corticosteroids
Measured: At 6 months
Diffusing capacity for carbon monoxide (DLCO)
Changes in % of predicted diffusing capacity for carbon monoxide (DLCO)
Measured: From baseline to 6 months
6 minutes walk test
Changes in the 6-minute walk test
Measured: From baseline to 6 months
Accelerometer-assessed physical activity
Change in accelerometer-assessed physical activity
Measured: From baseline to 6 months
Biological analyse on markers related to B-cell depletion
Changes of biological markers related to B-cell depletion
Measured: From baseline to 6 months
Environmental antigens
Changes of serology by ELISA of 15 environmental antigens.
Measured: From baseline to 6 months
High-resolution computed tomography (HRCT) of chest images
Changes in high-resolution computed tomography (HRCT) of chest images
Measured: From baseline to 6 months
Adverse events
Description of All adverse events, especially serious infectious adverse events, occurring during the six-month treatment period
Measured: From baseline to 6 months
Pharmacokinetic parameters of rituximab
Rituximab clearance
Measured: before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Pharmacokinetic parameters of rituximab
Volume of distribution
Measured: Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Pharmacokinetic parameters of rituximab
Half life
Measured: Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Severe Acute Respiratory Syndrome COronaVirus 2 (SARS COV 2) antibodies
Change of SARS COV 2 antibodies
Measured: From baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2022
- Study start16 Jan 2023
- Primary completion16 Jul 2026 (estimated)
- Study completion16 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung DiseasesStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julien LE BONNIEC, Study director, University Hospital Center of Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05596786
- Sponsor's protocol ID
- DR210299
- Acronym
- EvER-ILD2
- Status last verified
- Jul 2024
- First submitted
- 19 Oct 2022
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39693827Barnes H, Corte TJ, Keir G, Khor YH, Limaye S, Wrobel JP, Veitch E, Harrington J, Dowman L, Beckert L, Milne D, De Losa R, Cooper WA, Bell PT, Balakrishnan P, Troy LK. Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand. Respirology. 2024 Dec;29(12):1023-1046. doi: 10.1111/resp.14847. Epub 2024 Oct 28.
PubMed 39467777
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05596786
- Acronym / sponsor ID
- EvER-ILD2 / DR210299
- Conditions
- Lung Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 16 Jan 2023 (actual)
- Primary completion
- 16 Jul 2026 (estimated)
- Study completion
- 16 Jul 2026 (estimated)
- First posted
- 27 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituximab |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients ≥ 18 years old
- Who meet at least one of the following criteria for worsening ILD within 24 months:
- AND presence of an inflammatory component defined by
- Subjects covered by the French social security system
- Written informed consent obtained from subject
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabOne 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) | Drug | Rituximab |
| PlaceboOne 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) | Other | Placebo |
Primary outcome
Forced vital capacity
Time frame: From baseline to 6 months
The primary outcome is the change in Forced Vital Capacity (FVC) (in mL) from baseline to 6 months.
17 secondary outcomes
Forced vital capacity
Time frame: From baseline to 6 months
Progression free survival (PFS)
Time frame: At 6 months
King's Brief Interstitial Lung Disease (K-BILD) questionnaire
Time frame: From baseline to 6 months
L-PF symptom questionnaire
Time frame: From baseline to 6 months
L-PF impact questionnaire
Time frame: From baseline to 6 months
Cumulative doses of corticosteroids
Time frame: At 6 months
Diffusing capacity for carbon monoxide (DLCO)
Time frame: From baseline to 6 months
6 minutes walk test
Time frame: From baseline to 6 months
Accelerometer-assessed physical activity
Time frame: From baseline to 6 months
Biological analyse on markers related to B-cell depletion
Time frame: From baseline to 6 months
Environmental antigens
Time frame: From baseline to 6 months
High-resolution computed tomography (HRCT) of chest images
Time frame: From baseline to 6 months
Adverse events
Time frame: From baseline to 6 months
Pharmacokinetic parameters of rituximab
Time frame: before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Pharmacokinetic parameters of rituximab
Time frame: Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Pharmacokinetic parameters of rituximab
Time frame: Before and 2 hours after the end of each infusions, at 3 and 6 months after the first infusion
Severe Acute Respiratory Syndrome COronaVirus 2 (SARS COV 2) antibodies
Time frame: From baseline to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
- Derived from this study: PubMed 39693827Ferreira 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.
- Derived from this study: PubMed 39467777Barnes H, Corte TJ, Keir G, Khor YH, Limaye S, Wrobel JP, Veitch E, Harrington J, Dowman L, Beckert L, Milne D, De Losa R, Cooper WA, Bell PT, Balakrishnan P, Troy LK. Diagnosis and management of hypersensitivity pneumonitis in adults: A position statement from the Thoracic Society of Australia and New Zealand. Respirology. 2024 Dec;29(12):1023-1046. doi: 10.1111/resp.14847. Epub 2024 Oct 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien LE BONNIEC study director
University Hospital Center of Tours
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab in people with Lung Diseases, run by University Hospital, Tours at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sylvain MARCHAND ADAM, PhD (+33 2 47 47 98 34, sylvain.marchand-adam@univ-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced vital capacity (time frame: From baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05596786, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.