IVIG Treatment in Systemic Sclerosis

Study Overview
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Brief Summary
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The purpose of this research is to study the effects of Privigen (intravenous immunoglobulin) on the skin in patients with scleroderma. Approximately 24 subjects will take part in this investigator-initiated study at Georgetown University Hospital and Johns Hopkins Hospital. This study will last for one year (12 months). This research is being done because systemic sclerosis can cause severe, progressive organ involvement. The investigators hope this study treatment will improve the outcomes in this disease, including skin, muscle, joint, gastrointestinal, and lung involvement.

Detailed Description
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The investigators propose a double-blind controlled trial of 24 patients with Privigen® (Immune Globulin Intravenous (Human), 10% liquid treatment) with 3:1 randomization. Subjects with scleroderma will be given 2 g/kg/mo of Privigen® or placebo (Albuminar®-5) for 6 months. Scleroderma is generally a progressive disease, and while the skin does improve with time in some patients, others have progressive disease in spite of aggressive treatment. Also, spontaneous improvement in other organ systems is even less likely. Patients entered into the trial will have failed to respond to standard of care treatment over the past 4 months. Thus, the investigators feel that any actual improvement observed can be attributed to the IVIG treatment. Since this is a pilot study, future larger controlled trials will be necessary to clearly demonstrate the effectiveness, but the investigators are hoping that this study will give us signals that will guide the future clinical trial.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety and Efficacy of Intravenous Immunoglobulin Treatment in Patients With Systemic Sclerosis

Conditions
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Systemic Sclerosis, Diffuse Scleroderma

Intervention / Treatment
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* Biological: Privigen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diffuse systemic sclerosis with active skin involvement as defined as a mRSS >12, with no improvement or worsening in the previous 4 months in spite of treatment with methotrexate, cellcept, imuran, or anti-TNF agent; 18 years of age or older; Disease duration of less than 5 years from the first non-Raynaud's symptom of scleroderma. Exclusion Criteria: Use of more than 10 mg of prednisone, or any dose of cytoxan, d-penicillamine, or rituximab in the last 3 months; History of deep vein thrombosis (DVT), stroke, or other thromboembolic phenomenon; History of anaphylaxis or other serious reaction to human blood or blood products. Absolute IgA deficiency A prior receipt of IVIg treatment

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Privigen<br>Privigen is a ready-to-use, sterile, 10% protein liquid preparation of polyvalent human immunoglobulin G (IgG) for intravenous administration. Subjects will be given 2 g/kg/month of IVIGfor 6 months. Each dose will be split into 2 to 4 infusions on consecutive days to achieve the total monthly dose. | Biological: Privigen<br>* Subjects will receive 2 g/kg/mo of Privigen® for 6 months if randomized to the treatment group.<br>|
| Placebo Comparator: Placebo (Albuminar-5)<br>Albuminar-5 is a sterile solution of albumin obtained from large pools of adult human venous plasma and used as the placebo in this study. Albuminar-5 will be administered by the intravenous route and each dose will be split into 2 to 4 infusions on consecutive days to achieve the total monthly dose. | Biological: Privigen<br>* Subjects will receive 2 g/kg/mo of Privigen® for 6 months if randomized to the treatment group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study the effects of IVIG on the skin in patients with scleroderma | The modified Rodnan Skin Score (mRSS) will be used to determine the changes in skin | At the 4 month visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine any toxicity of IVIG in scleroderma | Laboratory assessments (Complete Blood Count (CBC) including liver and electrolytes with differentiation, Complete Metabolic Profile (CMP) including creatinine, and Coombs test) will be performed monthly to monitor toxicity. | At the 4 month visit | 
| To evaluate the effects of IVIG on pulmonary function | Pulmonary Function Tests (PFTs) will be performed to determine these changes. | At the 4 month visit | 
| Muscle, joint, and inflammatory parameters | Done by performing a physical exam | At the 4 month visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Sclerosis, Diffuse Scleroderma, SSc