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

CSL Behring

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Diffuse Cutaneous Systemic Sclerosis

Interventions

IgPro10BIOLOGICAL

10% liquid formulation of human immunoglobulin for IVIG

PlaceboBIOLOGICAL

0.5% human albumin solution stabilized with 250 mmol/L L-proline

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (77)

Outcomes

Primary Outcomes

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 Outcomes

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)

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)

Time frame: 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)

Data from ClinicalTrials.gov

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Mayo Clinic Arizona - Scottsdale

Scottsdale, Arizona, United States

Pacific Arthritis Care Center

Los Angeles, California, United States

University of California

Los Angeles, California, United States

Stanford University Medical Center

Palo Alto, California, United States

University of Colorado

Aurora, Colorado, United States

Lombardi Cancer Center-Georgetown University

Washington D.C., District of Columbia, United States

Alliance for Multispecialty Research

Wichita, Kansas, United States

Heartland Research Associates, LLC

Wichita, Kansas, United States

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

John Hopkins Bayview Medical Center

Baltimore, Maryland, United States

...and 67 more locations

Time frame: 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.

Time frame: Baseline and over 48 weeks

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

Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo

Time frame: 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

Time frame: 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

Time frame: Over 48 weeks

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