Study to Compare the Efficacy of Mycophenolate Mofetil in Systemic Sclerosis Related Early Interstitial Lung Disease

Study Overview
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Brief Summary
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Systemic sclerosis is a multisystem disease and can involve the lungs in the form of ILD. Lung involvement is the most common cause of death in these patients. The present study is performed to study the efficacy of oral mycophenolate mofetil in treating early and mild ILD in patients of SSc. The efficacy and side effects of mycophenolate mofetil will be compared with that of oral placebo.

Detailed Description
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Lung involvement is the leading cause of death among patients with systemic sclerosis (SSc). Treatment with immunosuppression drugs helps in retarding the progression of interstitial lung disease (ILD) and improves the morbidity and mortality among these patients. Presently, cyclophosphamide has been shown to be useful in stabilizing the lung functions among patients of systemic sclerosis with ILD. But use of cyclophosphamide is also associated with many adverse effects including infections, cytopenias, gonadal dysfunction and malignancies. Use of oral mycophenolate mofetil (MMF) in SSc-ILD in recent studies has been shown to be effective in retarding progression of ILD among these patients with a better side effect profile compared to cyclophosphamide. Contemporary expert opinion dictates that the treatment for SSc-ILD needs to be individualized. Generally, intense immunosuppression is required in patients with FVC <70% of the predicted. In patients with FVC >70% of the predicted, the need for high dose immunosuppression is not clear and varies from center-to-center. The present study is designed to determine the efficacy of oral MMF in patients with SSc related early ILD. The subjects in this study will be given either oral MMF or placebo and will be monitored for their response and adverse events. Informed consent will be taken from the subjects before including in the study.

Official Title
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A Randomized Controlled Trial to Compare the Efficacy of Oral Mycophenolate Mofetil With Placebo in Patients With Systemic Sclerosis Related Early Interstitial Lung Disease

Conditions
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Systemic Sclerosis, Scleroderma, Interstitial Lung Disease

Intervention / Treatment
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* Drug: Mycophenolate mofetil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of systemic sclerosis with presence of interstitial lung disease on High Resolution Computer Tomography (HRCT) chest FVC ≥ 70% of predicted on pulmonary function tests Age ≥18 years Consenting for participating in study Exclusion Criteria: Received immunosuppression (except low dose steroids, prednisolone equivalent ≤10 mg/day) for ILD in the last 3 years Persistent leucopenia or thrombocytopenia Pregnant or breastfeeding females Severe pulmonary arterial hypertension (mean pulmonary arterial pressure >55mmHg) requiring drug therapy Uncontrolled congestive heart failure Any other abnormalities noted on chest X-ray or HRCT other than ILD Active infection Inflammatory myositis Overlap syndrome Mixed connective tissue disease Other serious co-morbidities which could compromise patient's ability to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mycophenolate mofetil<br>Subjects will be started on Mycophenolate Mofetil 500mg twice a day and increased by 500mg every 2 weeks, if tolerated, to a target dose of 2gram per day. | Drug: Mycophenolate mofetil<br>* Subjects will be given oral Mycophenolate Mofetil starting at 500mg twice a day and increased gradually to a target dose of 2gram per day for 6 months<br>* Other names: MMF;|
| Placebo Comparator: Placebo<br>Subjects in this arm will be given matching placebo, made of lactulose, starting at two tablets per day and increased by one tablet every 2 weeks to a target of 4 tablets per day. | Drug: Placebo<br>* Subjects will be given matching placebo for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Forced vital capacity (FVC) at 6 months, after treatment with oral mycophenolate mofetil or placebo |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Quality of Life (QoL) score by Medical Outcome Short Form 36 (SF-36v2) at 6 months |  | 6 months | 
| Change from baseline in Mahler Dyspnoea Index (MDI) at 6 months |  | 6 months | 
| Number of participants with serious and non seroius adverse events with mycophenolate mofetil (MMF) and placebo |  | 6 months | 
| Change in Forced Vital Capacity (FVC) from baseline to 6 months according to antibody (anti-centromere and anti-topoisomerase1) profile |  | 6 months |