IVIG Treatment in Systemic Sclerosis

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

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.

Study Overview

• Status: Unknown
• Conditions: Systemic Sclerosis; Diffuse Scleroderma
• Intervention / Treatment: Biological: Privigen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Privigen; 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; Subjects will receive 2 g/kg/mo of Privigen® for 6 months if randomized to the treatment group.
Placebo Comparator: Placebo (Albuminar-5); 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; Subjects will receive 2 g/kg/mo of Privigen® for 6 months if randomized to the treatment group.

What is the study measuring?

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

Other 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 6 month visit
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 6 month visit
To evaluate the effects of IVIG on pulmonary function	Pulmonary Function Tests (PFTs) will be performed to determine these changes.	At the 6 month visit
To study the biologic effects of IVIG on gene arrays in skin biopsies	A skin biopsy will be taken at the Baseline and Month 6 visit to determine the biological effects of IVIG on the skin.	At the 6 month visit
Muscle, joint, and inflammatory parameters	A physical exam will be performed to determine these changes	At the 6 month visit

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: CSL Behring
• Investigators: Principal Investigator: Virginia D Steen, MD, Georgetown University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): January 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: January 28, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (Estimate): February 6, 2013

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 13, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Systemic Sclerosis; Diffuse Scleroderma; SSc
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: Pro00000052