Status:

NOT_YET_RECRUITING

Evaluation of Efficacy and Safety of Rituximab and Mycophenolate Mofetil Combination in Patients With Interstitial Lung Disease Related to Systemic Sclerosis

Lead Sponsor:

University Hospital, Tours

Conditions:

Interstitial Lung Disease With Systemic Sclerosis

Eligibility:

All Genders

18-100 years

Phase:

PHASE3

Brief 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...

Eligibility Criteria

Inclusion

  • Inclusion criteria
  • 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.
  • Exclusion Criteria:
  • 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
  • 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.

Exclusion

    Key Trial Info

    Start Date :

    November 15 2024

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    November 15 2028

    Estimated Enrollment :

    102 Patients enrolled

    Trial Details

    Trial ID

    NCT06549231

    Start Date

    November 15 2024

    End Date

    November 15 2028

    Last Update

    August 12 2024

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