Efficacy and Safety of IgPro10 in Adults With Systemic Sclerosis (SSc)

Study Overview
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Brief Summary
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This randomized, multicenter, double-blind (DB), placebo controlled, phase 2 study will evaluate the efficacy and safety of IgPro10. The DB Treatment Period will be followed by a 24-week Open-label (OL) Treatment Period. Eligible subjects will be randomized at Baseline in a 2:1 ratio of treatment IgPro10 or placebo in the DB Treatment Period. All subjects who enter OL Treatment Period will receive IgPro10.

Official Title
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A Randomized, Multicenter, Double-Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of IgPro10 (Intravenous Immunoglobulin, Privigen®) for the Treatment of Adults With Systemic Sclerosis

Conditions
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Diffuse Cutaneous Systemic Sclerosis

Intervention / Treatment
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* Biological: IgPro10
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age ≥18 years (male or female) at time of providing written informed consent Documented diagnosis of SSc according to ACR / EULAR criteria 2013 mRSS ≥ 15 and ≤ 45 Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation Subjects within first 18 months of disease duration from first non-Raynaud's phenomenon manifestation. Exclusion Criteria: Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, and dermatomyositis, as determined by the investigator Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy or myositis at Screening are not excluded Positive anti-centromere autoantibodies at Screening Evidence of severe chronic kidney disease with estimated glomerular filtration rate < 45 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation) or receiving dialysis. Additionally, subjects with current confirmed diagnosis of diabetes mellitus and requiring medication, with eGFR < 90 mL/min/1.73m2 will be excluded from the study. History of documented thrombotic episode eg, PE, DVT, myocardial infarction, thromboembolic stroke at any time Note: past superficial thrombophlebitis more than two years from Screening is not exclusionary Documented thrombophilic abnormalities including blood hyperviscosity, protein S or protein C deficiency, anti-thrombin-3 deficiency, plasminogen deficiency, antiphospholipid syndrome, Factor V Leiden mutation, dysfibrinogenemia, or prothrombin G20210A mutation Greater than 3 specified current risk factors for TEEs (documented and currents conditions): atrial fibrillation, coronary disease, diabetes mellitus, dyslipidemia, hypertension, obesity (Body Mass Index ≥ 30 kg/m2), recent significant trauma, and immobility (wheelchair-bound or bedridden) Ongoing active serious infection at Screening (including, but not limited to, pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, or visceral abscess) Malignancy in the past 2 years, except for non-melanoma skin cancer, cervical carcinoma in situ, or other in situ cancer if it has been excised and treated within in the past year Known hypoalbuminemia, protein-losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L) Known IgA deficiency or serum IgA level < 5% lower limit of normal

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro10<br>10% liquid formulation of human immunoglobulin for intravenous use | Biological: IgPro10<br>* 10% liquid formulation of human immunoglobulin for IVIG<br>* Other names: Human normal immunoglobulin;|
| Placebo Comparator: Placebo<br>0.5% human albumin solution stabilized with 250 mmol/L L-proline | Biological: Placebo<br>* 0.5% human albumin solution stabilized with 250 mmol/L L-proline<br>* Other names: Albumin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo |  | Over 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events |  | Over 48 weeks | 
| Proportion of responders (ACR CRISS > 0.6) |  | Over 48 weeks | 
| Mean change from Baseline in Modified Rodnan Skin Score (mRSS) |  | Baseline and over48 weeks | 
| Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) |  | Baseline and over 48 weeks | 
| Mean change from Baseline in Forced Vital Capacity (FVC)% predicted |  | Baseline and over 48 weeks | 
| Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted |  | Baseline and over 48 weeks | 
| Mean change from Baseline in Physician Global Assessment (MDGA) | MDGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor) | Baseline and over 48 weeks | 
| Mean change from Baseline in Patient Global Assessment (PGA) | PGA evaluates the overall impact of SSc on the participant as assessed by the physician on a 11-point Numeric rating scale scale from 0 (excellent) to 10 (extremely poor) | Baseline and over 48 weeks | 
| Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale | This survey consists of 34 questions and items are scored on a scale of 0 (better health) to 3 (worse health). Scores are combined to form total score. | Baseline and over 48 weeks | 
| Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo |  | Baseline and up to 48 weeks | 
| Proportion of responders in mRSS | Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo | Up to 48 weeks | 
| Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo | Treatment failure - defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all-cause mortality | Over 48 weeks | 
| Proportion of subjects with events at Week 48 in IgPro10 vs Placebo | Events defined as occurrence of SSc associated complications in ACR CRISS step 1 events, digital ischemia (requiring hospitalization for IV prostacyclin, surgical intervention or amputation), serious gastrointestinal events (events requiring parenteral nutrition due to SSc -such as total parenteral nutrition or enteral nutrition), all -cause mortality | Over 48 weeks | 
| Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo |  | Baseline and over 48 weeks | 
| Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo |  | Baseline and over 48 weeks | 
| Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo |  | Baseline and over 48 weeks | 
| Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) |  | Over 48 weeks | 
| Percentage of subjects with AEs, TEAEs, SAEs, AESIs |  | Over 48 weeks | 
| Concentration of serum trough IgG levels at Baseline and prior to first infusion |  | Baseline and up to 72 weeks | 
| Mean change from Baseline in Modified Rodnan skin score (mRSS) |  | Baseline and over 72 weeks | 
| Mean change from Baseline in Patient global assessment (PGA) |  | Baseline and over 72 weeks | 
| Proportion of responders (ACR CRISS > 0.6) |  | Over 72 weeks | 
| Mean change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) |  | Baseline and over 72 weeks | 
| Mean change from Baseline in Forced Vital Capacity (FVC)% predicted |  | Baseline and over 72 weeks | 
| Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted |  | Baseline and over 72 weeks | 
| Mean change from Baseline in Physician Global Assessment (MDGA) |  | Baseline and over 72 weeks | 
| Number of subjects with adverse events (AEs) including any AEs, treatment-emergent AEs (TEAEs), serious AEs (SAEs), and AEs of special interest (AESIs) |  | Over 72 weeks | 
| Percentage of subjects with AEs, TEAEs, SAEs, AESIs |  | Over 72 weeks |