Interstitial Lung Disease With Systemic SclerosisPhase 3EVER-ILD 3NCT06549231
Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis
A Phase 3 study testing Rituximab in people with Interstitial Lung Disease With Systemic Sclerosis, run by University Hospital, Tours at 1 site in France.
Trial summary
The goal of this clinical trial is to evaluate the efficacy on lung function after 24 weeks of rituximab + MMF combination comparatively to placebo + MMF combination in patients with SSc-ILD severe at the initial assessment or at high risk of progression. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Interstitial Lung Disease With Systemic Sclerosis
- 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
- 102 participants
- Where
- 1 siteFrance
- Study dates
- 8 Jan 2025to 8 Jan 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Male and female 18 years and older who meet the American College of Rheumatology/EUropean League Against Rheumatism collaborative initiative (ACR/EULAR) classification criteria 2013 for systemic scleroderma.
- Who are eligible for a treatment with MMF (up to 1500 mg twice daily if tolerated) for the management of SSc-ILD adapted from the French PNDS (revised may 2022) [9]:
- Severe ILD at the baseline assessment i. with an extensive ILD on HRCT ≥20% according to Goh classification [10] ii. or with forced vital capacity of the predicted value (% FVC) ≤ 70%.
- or ILD regardless of HRCT extension and at high risk of progression (age > 60 years, male gender, early cutaneous diffuse SSc (≤ 5 years), Afro-American or Afro-Caribbean ethnicity, anti-SCL70/Topoisomerase I autoantibody, or biological inflammation with CRP >= 5 mg/L).
- or ILD regardless of HRCT extension and with progression criteria in the past 6-24 months before the initial assessment (based on INBUILD study): i. relative decline in the forced vital capacity of the predicted value (% FVC) >=10% ii. or relative decline in FVC of 5-10% associated with a relative decline in DLCO >= 15% iii. or relative decline in FVC of 5-10% associated with worsening of dyspnea or extension of ILD lesion on HRCT iv. or worsening of dyspnea with extension of HRCT opacities
- Person affiliated to a French social security system or equivalent
- Written informed consent obtained from participant with a specific check box on the Consent form of the study, understanding the risk for men and women treated with mycophenolate mofetil. And additional written consent on the care and contraception agreement form for women of childbearing potential because of use of mycophenolate
- 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, sarcoidosis, smoking-related ILD), severe cardiomyopathy or a known severe heart failure as considered by the investigator
- Known diagnosis of group 1 precapillary pulmonary hypertension (mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance > 2 UWood and FVC ≥ 70% theoretical) or group 3 severe precapillary pulmonary hypertension (mPAP > 20 mmHg and PAWP ≤ 15 mmHg and pulmonary vascular resistance > 5 UWood, whatever the FVC)
- 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
- Patient who cannot walk more than 100 meters
- Known MMF intolerance
- Initiation of a new therapy for SSc-ILD or with interruption / modification of therapy dosage within 4 weeks prior to baseline assessment
Show all 15Show fewer
- Patient having already received a rituximab or MMF-based treatment line for SSc-ILD
- Known hypersensitivity to rituximab, to murine proteins, other excipients or sulphonamide antibiotics.
- Concomitant immunosuppressive treatments: >15 mg/day corticosteroids, azathioprine, cyclophosphamide, methotrexate, cyclosporine, tacrolimus, JAK inhibitors within 4 weeks prior to inclusion
- Treatment with monoclonal antibodies (such as, but not limited to, etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab, tocilizumab) within 6 months prior to inclusion
- Patients on a lung transplant list
- Persons covered by articles L1121-5 to L1121-8 of the CSP (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship). Also, women of child-bearing potential (including female partners of sexually active men treated with mycophenolate) not using two reliable contraceptive methods and men not using a contraceptive method (condom), or women and men having a pregnancy project during the year following randomization
- Patients at high risk of infectious complications: Human Immunodeficiency Virus (HIV) positive or other known immunodeficiency syndromes, hepatitis B and C (HBV, HCV), COVID (within 3 month) or other known viral infection, infection requiring anti-infective treatment within 4 weeks of inclusion
- Patients with incomplete anti-SARS-CoV-2 vaccine regimen (according to current recommendations) and in this case, patient who has not receive treatment with anti SARS CoV2 therapeutic antibodies (ex : tixagévimab/cilgavimab).
- Concomitant participation in other interventional research with an investigational drug or medical device.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU Tours
Tours
Sylvain MARCHAND ADAM, +33247479834, sylvain.marchand-adam@univ-tours.fr
About this study
Official title: Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis: a Multicentre Double-blind Placebo-controlled Randomized Trial.
The goal of this clinical trial is to evaluate the efficacy on lung function after 24 weeks of rituximab + MMF combination comparatively to placebo + MMF combination in patients with SSc-ILD severe at the initial assessment or at high risk of progression.
- Being tested
- Rituximab, Placebo
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 an infusion of 1000 mg rituximab (diluted in 500 mL of saline 0.9 % sodium chloride) will be given at day 1, day 15 and an infusion of 500 mg rituximab (in 500 mL of saline 0.9 % sodium chloride) at week 24;
PlaceboDrug
one course of intravenous placebo of rituximab consisting of an infusion of 500 mL of saline (0.9% sodium chloride) infusion will be given at day 1, day 15 and week 24;
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Not described Receives: Drug: Rituximab |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced vital Capacity in %
The primary outcome is the change in Forced Vital Capacity (FVC) (in % predicted) from baseline to week 24 with measures at baseline, week 12 and week 24.
Measured: At 24 weeks
Secondary outcomes (23)
Forced Vital Capacity in %
Change in % of predicted FVC (% FVC)
Measured: From baseline to weeks 48
Forced Vital Capacity in mL
Change in FVC (mL)
Measured: From baseline to weeks 24 and 48
Rodnan skin score
Change in modified Rodnan skin score (mRSS). This score assesses the extent of thickening at 17 points on the body, simply by palpating the skin. Thickening is from 0 to 3. 0 equals to normal skin thickness and 3 to severe thickening.
Measured: From baseline to weeks 24 and 48
Progression free survival
First event considered
Measured: At 24 and 48 weeks
Overall survival
Measured: At 48 weeks
Scleroderma Health Assessment questionnaire
23 questions divided into four groups related to symptoms of vascular, respiratory, gastrointestinal and musculoskeletal dysfunction
Measured: From baseline to weeks 24 and 48
King's Brief Interstitial Lung Disease questionnaire
15 questions about the impact of the disease on life. All answers are from 1 to 7. There is no maximum and minimum.
Measured: From baseline to weeks 24 and 48
Living with pulmonary fibrosis symptom questionnaire
23 questions to evaluate symptoms of pulmonary fibrosis
Measured: From baseline to weeks 24 and 48
Living with pulmonary fibrosis impact questionnaire
21 questions to determine how pulmonary fibrosis affects quality of life.
Measured: From baseline to weeks 24 and 48
Diffusing capacity for carbon monoxide
Changes in % of predicted diffusing capacity for carbon monoxide
Measured: From baseline to weeks 24 and 48
6 minutes walk test
Changes in the 6 minute walk test
Measured: From baseline to weeks 24 and 48
Physical activity
Change in accelerometer-assessed physical activity based on the number of steps per day
Measured: From baseline to week 24
Physical activity
Change in accelerometer-assessed physical activity based on heart rate
Measured: From baseline to week 24
Chest image
Changes in HRCT chest images will be assessed by two thoracic radiologists expert in ILDs, who will score the extent of ILD and the severity of traction bronchiectasis. The ILD extent score will be estimated to the nearest 10% at three lung zones (delimited by the carina and the lowest inferior pulmonary vein for both lungs) and averaged between these 3 zones. Traction bronchiectasis scores will be scored between 0 and 3 (0=absence; 1=mild dilatation without tortuosity; 2=moderate dilatation, < 6mm diameter, with tortuosity; 3=severe dilatation≥ 6mm) for the same three lung zones and averaged for the whole lungs.
Measured: From baseline to week 48
Biological markers
Changes of biological markers related to B-cell depletion. Change in the number of CD19 lymphocytes in absolute value/liter
Measured: From baseline to week 48
Biological markers
Changes of biological markers related to B-cell depletion. Change in the number of CD19 lymphocytes in percentage of leukocytes
Measured: From baseline to week 48
Biological markers
Changes of biological markers related to B-cell depletion. Change in serum gamma globulin concentration in grams/liter
Measured: From baseline to week 48
Biological markers
Changes of biological markers related to B-cell depletion. Change in serum gamma globulin concentration as a percentage of serum proteins
Measured: From baseline to week 48
Advers events
Analyze of all adverse events, especially serious infectious adverse events, occurring during treatment period
Measured: From baseline to week 48
Pharmacokinetic
Pharmacokinetic parameters of rituximab : volume of distribution in liter
Measured: At Day 1, day 15, week 12, week 24 and week 48
Pharmacokinetic
Pharmacokinetic parameters of rituximab : clearance in mili liter per minute
Measured: At Day 1, day 15, week 12, week 24 and week 48
Pharmacokinetic
Pharmacokinetic parameters of rituximab : half life in secondes
Measured: At Day 1, day 15, week 12, week 24 and week 48
Cumulative doses of corticosteroids
Measured: At week 24 and week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2024
- Study start8 Jan 2025
- Primary completion8 Jul 2028 (estimated)
- Study completion8 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Interstitial Lung Disease With Systemic SclerosisStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06549231
- Sponsor's protocol ID
- DR230333
- Acronym
- EVER-ILD 3
- Status last verified
- Jun 2026
- First submitted
- 15 Jul 2024
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis: a Multicentre Double-blind Placebo-controlled Randomized Trial.
- ClinicalTrials.gov ID
- NCT06549231
- Acronym / sponsor ID
- EVER-ILD 3 / DR230333
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 8 Jan 2025 (actual)
- Primary completion
- 8 Jul 2028 (estimated)
- Study completion
- 8 Jan 2029 (estimated)
- First posted
- 12 Aug 2024 (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 goal of this clinical trial is to evaluate the efficacy on lung function after 24 weeks of rituximab + MMF combination comparatively to placebo + MMF combination in patients with SSc-ILD severe at the initial assessment or at high risk of progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituximab |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female 18 years and older who meet the American College of Rheumatology/EUropean League Against Rheumatism collaborative initiative (ACR/EULAR) classification criteria 2013 for systemic scleroderma.
- Who are eligible for a treatment with MMF (up to 1500 mg twice daily if tolerated) for the management of SSc-ILD adapted from the French PNDS (revised may 2022) [9]:
- Person affiliated to a French social security system or equivalent
- Written informed consent obtained from participant with a specific check box on the Consent form of the study, understanding the risk for men and women treated with mycophenolate mofetil. And additional written consent on the care and contraception agreement form for women of childbearing potential because of use of mycophenolate
- Ability for subject to comply with the requirements of the study.
Key exclusion criteria (15 listed)
- Known diagnosis of significant respiratory disorders (asthma, tuberculosis, aspergillosis, cystic fibrosis, idiopathic pulmonary fibrosis, sarcoidosis, smoking-related ILD), severe cardiomyopathy or a known severe heart failure as considered by the investigator
- Known diagnosis of group 1 precapillary pulmonary hypertension (mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance > 2 UWood and FVC ≥ 70% theoretical) or group 3 severe precapillary pulmonary hypertension (mPAP > 20 mmHg and PAWP ≤ 15 mmHg and pulmonary vascular resistance > 5 UWood, whatever the FVC)
- 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
- Patient who cannot walk more than 100 meters
- Known MMF intolerance
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 an infusion of 1000 mg rituximab (diluted in 500 mL of saline 0.9 % sodium chloride) will be given at day 1, day 15 and an infusion of 500 mg rituximab (in 500 mL of saline 0.9 % sodium chloride) at week 24; | Drug | Rituximab |
| Placeboone course of intravenous placebo of rituximab consisting of an infusion of 500 mL of saline (0.9% sodium chloride) infusion will be given at day 1, day 15 and week 24; | Drug | Placebo |
Primary outcome
Forced vital Capacity in %
Time frame: At 24 weeks
The primary outcome is the change in Forced Vital Capacity (FVC) (in % predicted) from baseline to week 24 with measures at baseline, week 12 and week 24.
23 secondary outcomes
Forced Vital Capacity in %
Time frame: From baseline to weeks 48
Forced Vital Capacity in mL
Time frame: From baseline to weeks 24 and 48
Rodnan skin score
Time frame: From baseline to weeks 24 and 48
Progression free survival
Time frame: At 24 and 48 weeks
Overall survival
Time frame: At 48 weeks
Scleroderma Health Assessment questionnaire
Time frame: From baseline to weeks 24 and 48
King's Brief Interstitial Lung Disease questionnaire
Time frame: From baseline to weeks 24 and 48
Living with pulmonary fibrosis symptom questionnaire
Time frame: From baseline to weeks 24 and 48
Living with pulmonary fibrosis impact questionnaire
Time frame: From baseline to weeks 24 and 48
Diffusing capacity for carbon monoxide
Time frame: From baseline to weeks 24 and 48
6 minutes walk test
Time frame: From baseline to weeks 24 and 48
Physical activity
Time frame: From baseline to week 24
Physical activity
Time frame: From baseline to week 24
Chest image
Time frame: From baseline to week 48
Biological markers
Time frame: From baseline to week 48
Biological markers
Time frame: From baseline to week 48
Biological markers
Time frame: From baseline to week 48
Biological markers
Time frame: From baseline to week 48
Advers events
Time frame: From baseline to week 48
Pharmacokinetic
Time frame: At Day 1, day 15, week 12, week 24 and week 48
Pharmacokinetic
Time frame: At Day 1, day 15, week 12, week 24 and week 48
Pharmacokinetic
Time frame: At Day 1, day 15, week 12, week 24 and week 48
Cumulative doses of corticosteroids
Time frame: At week 24 and week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
Related trials for Interstitial Lung Disease With Systemic Sclerosis
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
RecruitingPhase 2/3
RESET-SSc: An Open-Label Study to Evaluate the Safety and Efficacy of CABA-201, a CD19-CAR T Cell Therapy, in Subjects With Systemic Sclerosis
Systemic Sclerosis, Scleroderma
Not yet recruitingPhase 1
A Study of BMS-986553 in Participants With Refractory Autoimmune Diseases
Systemic Lupus Erythematosus, Sjögren's Disease
Active, not recruitingPhase 3
Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
Systemic Sclerosis, Scleroderma
RecruitingPhase 2
Mycophenolate Mofetil in Systemic Sclerosis With Subclinical Interstitial Lung Disease
Systemic Sclerosis With Lung Involvement, Systemic Sclerosis
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.
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 Interstitial Lung Disease With Systemic Sclerosis, 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 8 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: looking for participants now, as of the sponsor's last update on 12 Jun 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced vital Capacity in % (time frame: At 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jun 2026.