Evaluation of Efficacy and Safety of Rituximab With Mycophenolate Mofetil in Patients With Interstitial Lung Diseases

NCT ID: NCT02990286

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

122 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-20

Study Completion Date

2020-02-17

Brief Summary

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The purpose of the study is to evaluate the efficacy on lung function 6 months after one course of rituximab (2 infusions) and mycophénolate mofétil (MMF) treatment compared to one course of placebo and 6 months of MMF treatment in a broad range of patients with Interstitial Lung Diseases (ILD) non-responders to a first line immunosuppressive treatment.

Detailed Description

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Conditions

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Lung Disease, Interstitial

Keywords

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Non specific intertitial pneumonia interstitial pneumonia with autoimmune feature connective tissue disease rituximab Mycophenolate Mofetil pulmonary fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Rituximab with Mycophenolate Mofetil

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Rituximab 500mg concentrate for solution for infusion. One course of IV rituximab consisting of a first infusion of 1000 mg (500 ml solution) rituximab (day 1 infusion), and a second infusion of 1000 mg (500 ml solution) rituximab two weeks later (day 15 infusion)

Mycophenolate Mofetil

Intervention Type DRUG

Mycophenolate Mofetil 500mg film-coated tablets

1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.

Placebo of rituximab with Mycophenolate Mofetil

Group Type PLACEBO_COMPARATOR

Placebo of Rituximab

Intervention Type DRUG

500 ml of saline (0.9% sodium chloride) for infusion One course of intravenous placebo of rituximab consisting of a first infusion of 500 ml of saline (0.9% sodium chloride) infusion (day 1 infusion), and a second infusion of 500 ml of saline infusion two weeks later (day 15 infusion)

Mycophenolate Mofetil

Intervention Type DRUG

Mycophenolate Mofetil 500mg film-coated tablets

1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.

Interventions

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Rituximab

Rituximab 500mg concentrate for solution for infusion. One course of IV rituximab consisting of a first infusion of 1000 mg (500 ml solution) rituximab (day 1 infusion), and a second infusion of 1000 mg (500 ml solution) rituximab two weeks later (day 15 infusion)

Intervention Type DRUG

Placebo of Rituximab

500 ml of saline (0.9% sodium chloride) for infusion One course of intravenous placebo of rituximab consisting of a first infusion of 500 ml of saline (0.9% sodium chloride) infusion (day 1 infusion), and a second infusion of 500 ml of saline infusion two weeks later (day 15 infusion)

Intervention Type DRUG

Mycophenolate Mofetil

Mycophenolate Mofetil 500mg film-coated tablets

1 gram twice daily on oral route of MMF (= 2 grams daily) for 6 months.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years
2. A diagnosis of ILD:

* ILD associated with differentiated CTD or IPAF (based on internationally accepted criteria)
* OR idiopathic ILD
3. A diagnosis of NSIP based on:

* a histological pattern of NSIP
* OR HRCT findings suggestive of NSIP defined as basal predominant reticular abnormalities with traction bronchiectasis, peri-bronchovascular extension and subpleural sparing, frequently associated with ground-glass attenuation
4. Patients who did not respond or relapsed or were not able to continue at least one first-line immunosuppressive treatment of ILD: corticosteroids, azathioprine, cyclophosphamide or other immunosuppressants. For the assessment of clinical response, the absence of response was defined as: either a decrease or an increase, but \<10% in % predicted FVC.
5. Subjects covered by or having the rights to French social security (including CMU),
6. Written informed consent obtained from subject, 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 from subject on the care and contraception agreement form for women of childbearing potential treated with mycophenolate.
7. Ability for subject to comply with the requirements of the study

Exclusion Criteria

1. Known diagnosis of significant respiratory disorders (asthma, tuberculosis, sarcoidosis, aspergillosis, or cystic fibrosis) other than CTD-NSIP, IPAF-NSIP and iNSIP
2. Evidence of any clinically significant, severe or unstable, acute or chronically progressive cardiac (severe heart failure New York Heart Association Class IV or severe uncontrolled cardiac disease), other medical disease (other than NSIP) or surgical disorder, or any condition that may affect patient safety in the judgment of the investigator.
3. HRCT pattern of typical usual interstitial pneumonia (UIP)
4. For patients with idiopathic ILD, HRCT pattern of possible UIP (no evocative of NSIP)
5. Histological pattern other than pattern of NSIP
6. A first line treatment with MMF or rituximab
7. Known hypersensitivity to MMF or rituximab or sulfonamide antibiotics
8. Treatment with immunosuppressive treatments other than corticosteroids:

* azathioprine, cyclophosphamide, methotrexate, cyclosporine, tacrolimus, leflunomide within 2 weeks (5 half-lives \<= 2 weeks) prior to inclusion
* intravenous immunoglobulins, hydroxychloroquine or other monoclonal antibody therapies (such as but not limited to etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab) within 6 months (5 half-lives \<= 6 months) prior to inclusion
9. Patients registered on a pulmonary transplantation list
10. Patients with known hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) hereditary deficiency (such as Lesch-Nyhan and Kelley-Seegmiller syndrome)
11. Pregnant or breastfeeding women, or women of child-bearing potential not using two reliable contraceptive methods (including female partners of sexually active men treated with mycophenolate) and men not using a contraceptive method (condom), or women and men having a pregnancy project during the year following randomization.
12. Patients at significant risk for infectious complications: HIV positive, other known immunodeficiency syndromes, untreated tuberculosis, hepatitis B and C or other known viral infection, infection requiring anti-infectious treatment in the preceding 4 weeks
13. Current history of substance and/or alcohol abuse
14. Deprivation of liberty, under judicial protection
15. Participation in another biomedical research with experimental drug or medical device
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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TRACLET Julie

Role: PRINCIPAL_INVESTIGATOR

HC LYON

NUNES Hilario

Role: PRINCIPAL_INVESTIGATOR

AP-HP - Hôpital Avicenne

CRESTANI Bruno

Role: PRINCIPAL_INVESTIGATOR

AP-HP - Hôpital Bichat

ISRAEL BIET Dominique

Role: PRINCIPAL_INVESTIGATOR

AP-HP HEGP

NACCACHE Jean-Marc

Role: PRINCIPAL_INVESTIGATOR

AP-HP - Hôpital Tenon

WEMEAU Lidwine

Role: PRINCIPAL_INVESTIGATOR

CHRU LILLE

JOUNEAU Stéphane

Role: PRINCIPAL_INVESTIGATOR

CHU Rennes

PREVOT Grégoire

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

REYNAUD-GAUBERT Martine

Role: PRINCIPAL_INVESTIGATOR

AP-HM Hôpital Nord

HIRSCHI SANTELMO Sandrine

Role: PRINCIPAL_INVESTIGATOR

CHRU Strasbourg

GONDOUIN Anne

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Besancon

COURT-FORTUNE Isabelle

Role: PRINCIPAL_INVESTIGATOR

CHU ST-ETIENNE

BONNIAUD Philippe

Role: PRINCIPAL_INVESTIGATOR

CHU DIJON

QUETANT Sébastien

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

GOMEZ Emmanuel

Role: PRINCIPAL_INVESTIGATOR

CHU NANCY

BLANC François-Xavier

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

MARQUETTE Charles-Hugo

Role: PRINCIPAL_INVESTIGATOR

CHU NICE

MARCHAND-ADAM Sylvain

Role: PRINCIPAL_INVESTIGATOR

CHRU TOURS

Locations

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Chu Besancon

Besançon, , France

Site Status

Chu Dijon

Dijon, , France

Site Status

AP-HM Hôpital NORD

Marseille, , France

Site Status

Chu Rennes

Rennes, , France

Site Status

CHRU Tours

Tours, , France

Site Status

Countries

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France

References

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Mankikian J, Caille A, Reynaud-Gaubert M, Agier MS, Bermudez J, Bonniaud P, Borie R, Brillet PY, Cadranel J, Court-Fortune I, Crestani B, Debray MP, Gomez E, Gondouin A, Hirschi-Santelmo S, Israel-Biet D, Jouneau S, Juvin K, Leger J, Kerjouan M, Marquette CH, Naccache JM, Nunes H, Plantier L, Prevot G, Quetant S, Traclet J, Valentin V, Uzunhan Y, Wemeau-Stervinou L, Bejan-Angoulvant T, Cottin V, Marchand-Adam S; EVER-ILD investigators and the OrphaLung network. Rituximab and mycophenolate mofetil combination in patients with interstitial lung disease (EVER-ILD): a double-blind, randomised, placebo-controlled trial. Eur Respir J. 2023 Jun 8;61(6):2202071. doi: 10.1183/13993003.02071-2022. Print 2023 Jun.

Reference Type RESULT
PMID: 37230499 (View on PubMed)

Bejan-Angoulvant T, Naccache JM, Caille A, Borie R, Nunes H, Ferreira M, Cadranel J, Crestani B, Cottin V, Marchand-Adam S; OrphaLung. Evaluation of efficacy and safety of rituximab in combination with mycophenolate mofetil in patients with nonspecific interstitial pneumonia non-responding to a first-line immunosuppressive treatment (EVER-ILD): A double-blind placebo-controlled randomized trial. Respir Med Res. 2020 Nov;78:100770. doi: 10.1016/j.resmer.2020.100770. Epub 2020 May 23.

Reference Type DERIVED
PMID: 32777737 (View on PubMed)

Other Identifiers

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PHRN15-SMA/EvER-ILD

Identifier Type: -

Identifier Source: org_study_id