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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: September 16, 2020

Interventions

  • Biological: IgPro10
    • 10% liquid formulation of human immunoglobulin for IVIG
  • Biological: Placebo
    • 0.5% human albumin solution stabilized with 250 mmol/L L-proline

Arms, Groups and Cohorts

  • Experimental: IgPro10
    • 10% liquid formulation of human immunoglobulin for intravenous use
  • Placebo Comparator: Placebo
    • 0.5% human albumin solution stabilized with 250 mmol/L L-proline

Clinical Trial Outcome Measures

Primary Measures

  • Response on American College of Rheumatology Combined Response Index in Diffuse Systemic Sclerosis (ACR CRISS) score in IgPro10 vs Placebo
    • Time Frame: Over 48 weeks

Secondary Measures

  • Proportion of subjects meeting cardiopulmonary or renal failure criteria in ACR CRISS Step 1 events
    • Time Frame: Over 48 weeks
  • Proportion of responders (ACR CRISS > 0.6)
    • Time Frame: Over 48 weeks
  • Mean change from Baseline in Modified Rodnan Skin Score (mRSS)
    • Time Frame: Baseline and over48 weeks
  • Mean change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI)
    • Time Frame: Baseline and over 48 weeks
  • Mean change from Baseline in Forced Vital Capacity (FVC)% predicted
    • Time Frame: Baseline and over 48 weeks
  • Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted
    • Time Frame: Baseline and over 48 weeks
  • Mean change from Baseline in Physician Global Assessment (MDGA)
    • Time Frame: Baseline and over 48 weeks
    • 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)
  • Mean change from Baseline in Patient Global Assessment (PGA)
    • Time Frame: Baseline and over 48 weeks
    • 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)
  • Mean change from Baseline in UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) total score and subscale
    • Time Frame: Baseline and over 48 weeks
    • 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.
  • Mean change from Baseline in Scleroderma Skin Patient Reported Outcome (SSPRO) score in IgPro10 vs Placebo
    • Time Frame: Baseline and up to 48 weeks
  • Proportion of responders in mRSS
    • Time Frame: Up to 48 weeks
    • Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo
  • Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo
    • Time Frame: Over 48 weeks
    • 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
  • Proportion of subjects with events at Week 48 in IgPro10 vs Placebo
    • Time Frame: Over 48 weeks
    • 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
  • Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo
    • Time Frame: Baseline and over 48 weeks
  • Mean change from Baseline in Scleroderma Health Assessment Questionnaire (SHAQ) score in IgPro10 vs Placebo
    • Time Frame: Baseline and over 48 weeks
  • Mean change from baseline in muscle strength as measured by Manual Muscle Testing 8 (MMT) in IgPro10 vs Placebo
    • Time Frame: 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)
    • Time Frame: Over 48 weeks
  • Percentage of subjects with AEs, TEAEs, SAEs, AESIs
    • Time Frame: Over 48 weeks
  • Concentration of serum trough IgG levels at Baseline and prior to first infusion
    • Time Frame: Baseline and up to 72 weeks
  • Mean change from Baseline in Modified Rodnan skin score (mRSS)
    • Time Frame: Baseline and over 72 weeks
  • Mean change from Baseline in Patient global assessment (PGA)
    • Time Frame: Baseline and over 72 weeks
  • Proportion of responders (ACR CRISS > 0.6)
    • Time Frame: Over 72 weeks
  • Mean change from Baseline in Health Assessment Questionnaire – Disability Index (HAQ-DI)
    • Time Frame: Baseline and over 72 weeks
  • Mean change from Baseline in Forced Vital Capacity (FVC)% predicted
    • Time Frame: Baseline and over 72 weeks
  • Mean change from Baseline in diffusing capacity of lung for carbon monoxide (DLCO)% predicted
    • Time Frame: Baseline and over 72 weeks
  • Mean change from Baseline in Physician Global Assessment (MDGA)
    • Time Frame: 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)
    • Time Frame: Over 72 weeks
  • Percentage of subjects with AEs, TEAEs, SAEs, AESIs
    • Time Frame: Over 72 weeks

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • CSL Behring
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Study Director, Study Director, CSL Behring

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