Safety and Pharmacokinetics of IgPro20 and IgPro10 in Adults With Systemic Sclerosis (SSc)

Study Overview
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Brief Summary
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This is a prospective, multicenter, randomized, open-label, crossover study to investigate the safety, tolerability, and pharmacokinetics of IgPro20 in subjects with diffuse cutaneous systemic sclerosis (dcSSc). The pharmacokinetic study aims to evaluate the relative bioavailability of IgPro20, and characterize pharmacokinetics of IgPro20 and IgPro10, respectively, in subjects with dcSSc. Safety, tolerability, and pharmacokinetics of IgPro10 will also be evaluated.

Official Title
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A Multicenter, Randomized, Open-label, Crossover, Phase 2 Study to Evaluate the Safety and Pharmacokinetics of IgPro20 (Subcutaneous Immunoglobulin, Hizentra®) and IgPro10 (Intravenous Immunoglobulin, Privigen®) in Adults With Systemic Sclerosis (SSc)

Conditions
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Diffuse Cutaneous Systemic Sclerosis

Intervention / Treatment
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* Biological: IgPro20
* Biological: IgPro10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years (male or female) at time of providing written informed consent Documented diagnosis of systemic sclerosis (scleroderma) according to American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria 2013 (diffuse cutaneous form of SSc). Modified Rodnan Skin Score (mRSS) ≥ 15 and ≤ 45 at screening Disease duration ≤ 5 years defined as the time from the first non-Raynaud's phenomenon manifestation Capable of providing written informed consent and willing and able to adhere to all protocol requirements Exclusion Criteria: Primary rheumatic autoimmune disease other than dcSSc, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disorder, polymyositis, dermatomyositis, as determined by the investigator. Note: Subjects with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy at screening are not excluded Subject has mRSS > 2 at the potential subcutaneous (SC) infusion sites History of skin condition precluding SC infusion, or clinical signs and symptoms of a chronic skin disease other than systemic sclerosis or skin manifestation of an allergic disease or other dermatological conditions that would interfere with trial assessments or compromise safety (eg, dermatitis, eczema, psoriasis) Subject has clinical signs and symptoms of skin irritation (eg, pruritus, burning, erythema) or hypo/ hyperpigmentation (eg, scars, tattoos) at the potential SC infusion sites Significant pulmonary arterial hypertension as documented by mean pulmonary arterial pressure > 30 mmHg on right heart catheterization requiring SC or IV prostacyclin or use of dual oral therapies Forced vital capacity < 50% predicted or a diffusing capacity of the lung for carbon dioxide (DLCO) ≤ 40% predicted (corrected for hemoglobin) A female who is pregnant, breastfeeding, or is a woman of childbearing potential who does not agree to use acceptable methods of contraception; a male who does agree to use acceptable methods of contraception. Evidence of chronic kidney disease with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 or if subject is receiving dialysis. Subjects with current confirmed diagnosis of diabetes mellitus requiring medication with an eGFR < 90 ml/min/1.73m2

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IgPro20<br>20% liquid formulation of human immunoglobulin for subcutaneous use | Biological: IgPro20<br>* Human normal immunoglobulin for subcutaneous administration<br>* Other names: Hizentra;|
| Experimental: IgPro10<br>10% liquid formulation of human immunoglobulin for intravenous use | Biological: IgPro10<br>* Human normal immunoglobulin for intravenous administration<br>* Other names: Privigen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) for IgPro20 |  | Up to 16 weeks | 
| Percentage of subjects with AEs for IgPro20 |  | Up to 16 weeks | 
| Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro20 |  | Up to 16 weeks | 
| Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro20 |  | Up to 16 weeks | 
| Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro20 |  | Up to 16 weeks | 
| Number of patients with AEs categorized as infusion site reactions (ISRs) for IgPro20 |  | Up to 16 weeks | 
| Percentage of patients with AEs categorized as ISRs for IgPro20 |  | Up to 16 weeks | 
| Rate of ISRs per subject for IgPro20 |  | Up to 16 weeks | 
| Rate of ISRs per infusion for IgPro20 |  | Up to 16 weeks | 
| Onset of ISRs for IgPro20 |  | Up to 16 weeks | 
| Duration of ISRs for IgPro20 |  | Up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgPro20 relative bioavailability (%F) |  | Up to 16 weeks | 
| Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro20 |  | Up to 240 hours after first infusion | 
| Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro20 |  | Up to 240 hours after first infusion | 
| Maximum plasma drug concentration (Cmax) for IgPro20 |  | Up to 240 hours after first infusion | 
| Minimum plasma drug concentration (Ctrough) for IgPro20 |  | Prior to infusion | 
| Area under the concentration curve to the end of the dosing period (AUC0-tau) for IgPro10 |  | Up to 672 hours after first infusion | 
| Area under the concentration curve up to the last measurable concentration (AUC0-last) for IgPro10 |  | Up to 672 hours after first infusion | 
| Maximum plasma drug concentration (Cmax) for IgPro10 |  | Up to 672 hours after first infusion | 
| Minimum plasma drug concentration (Ctrough) for IgPro10 |  | Prior to infusion | 
| Number and percentage of subjects with AEs for IgPro10 |  | Up to 16 weeks | 
| Number and percentage of subjects with treatment emergent adverse events (TEAEs) for IgPro10 |  | Up to 16 weeks | 
| Number and percentage of subjects with seriouis adverse events (SAEs) for IgPro10 |  | Up to 16 weeks | 
| Number and percentage of subjects with adverse events of special interest (AESIs) for IgPro10 |  | Up to 16 weeks | 
| Number and percentage of subjects with AEs categorized as ISRs for IgPro10 |  | Up to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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scleroderma