Diffuse Cutaneous Systemic Sclerosis
Conditions
Brief summary
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.
Interventions
BIOLOGICALIgPro10
10% liquid formulation of human immunoglobulin for IVIG
BIOLOGICALPlacebo
0.5% human albumin solution stabilized with 250 mmol/L L-proline
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) | 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 | 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 | Baseline and up to 48 weeks | — |
| Mean change from Baseline in Cochin Hand Function Scale in IgPro10 vs Placebo | Baseline and over 48 weeks | — |
| Time to treatment failure (time from first infusion to time of first event) in IgPro10 vs Placebo | 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 | 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 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 in mRSS | Up to 48 weeks | Response is decrease of mRSS ≥ 5 points and change of ≥ 25% from Baseline in IgPro10 vs Placebo |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Italy, Mexico, Poland, Spain, Switzerland, United Kingdom, United States
Outcome results
None listed