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

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)

This is a prospective, multicenter, randomized, open-label, crossover study to investigate the safety, tolerability, and pharmacokinetics of IgPro20 in participants 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 participants with dcSSc. Safety, tolerability, and pharmacokinetics of IgPro10 will also be evaluated.

Study Overview

• Status: Completed
• Conditions: Diffuse Cutaneous Systemic Sclerosis
• Intervention / Treatment: Biological: IgPro20; Biological: IgPro10

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin
  • Köln, Germany, 50937
    • Uniklinik Köln, innere Medizin
• Italy
  • Brescia, Italy, 25123
    • ASST Spedali Civili di Brescia
  • Milano, Italy, 20122
    • Azienda Ospedaliera Gaetano Pini
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczny w Bialymstoku
  • Warsaw, Poland, 02-008
    • Szpital Kliniczny Jezus
  • Warsaw, Poland, 02-637
    • Narodowy Instytut Geriatrii
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • The Royal Free Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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: Participants with fibromyalgia, secondary Sjogren's syndrome, and scleroderma-associated myopathy at screening are not excluded
• Participants has mRSS > 2 at the potential subcutaneous (SC) injection 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)
• Participants has clinical signs and symptoms of skin irritation (eg, pruritus, burning, erythema) or hypo/ hyperpigmentation (eg, scars, tattoos) at the potential SC injection 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 participants are receiving dialysis. Participants with current confirmed diagnosis of diabetes mellitus requiring medication with an eGFR < 90 ml/min/1.73m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A (IgPro20/IgPro10); Participants received IgPro20 of a total dose of 0.5 grams per kilogram (g/kg) over 2 sessions per week as a subcutaneous (SC) injection for up to 16 weeks in Treatment Period 1 followed by IgPro10 of a total dose of 2 g/kg over 2 to 5 sessions on consecutive days every 4 weeks as an intravenous (IV) infusion for up to 16 weeks in Treatment Period 2.	Biological: IgPro20; Human normal immunoglobulin for subcutaneous administration; Other Names: Hizentra; Biological: IgPro10; Human normal immunoglobulin for intravenous administration; Other Names: Privigen
Experimental: Sequence B (IgPro10/IgPro20); Participants received IgPro10 of a total dose of 2 g/kg over 2 to 5 sessions on consecutive days every 4 weeks as an IV infusion for up to 16 weeks in Treatment Period 1 followed by IgPro20 of a total dose of 0.5 g/kg over 2 sessions per week as a SC injection for up to 16 weeks in Treatment Period 2.	Biological: IgPro20; Human normal immunoglobulin for subcutaneous administration; Other Names: Hizentra; Biological: IgPro10; Human normal immunoglobulin for intravenous administration; Other Names: Privigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Adverse Event (AE) for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Percentage of Participants With at Least One AE for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Percentage of Participants With at Least One TEAE for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20	An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Percentage of Participants With at Least One SAE for IgPro20	An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.	From first dose of study drug through last follow-up visit (up to 36 weeks)
Percentage of Participants With at Least One AESI for IgPro20	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With AEs Categorized as ISRs for IgPro20	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.	From first dose of study drug through last follow up visit (up to 36 weeks)
Rate of ISRs Per Infusion for IgPro20	ISR rate per infusion = total number of ISRs across all participants while on IgPro20 / total number of IgPro20 Infusions across all participants. ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions NEC', 'Infusion site reactions', or 'Injection site reactions'	From first dose of study drug through last follow up visit (up to 36 weeks)
Time to Onset of ISRs for IgPro20	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. Time to onset of ISR since the start of the treatment period was reported.	From first dose of study drug through last follow up visit (up to 36 weeks)
Duration of ISRs for IgPro20	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20	Abnormality criteria:Hematology-Hemoglobin:<10 g/dL;Platelet count:<75x10^9/L or >500x10^9/L;White Blood Cell Count:<3x10^9/L or >16x10^9/L;Neutrophils:absolute <1.5x10^9/L,differential <40%;Lymphocytes:absolute <0.8x10^9/L,differential <10 or >50%; Biochemistry-Bilirubin:>1.5xupper limit of normal (ULN);Alkaline phosphatase:>2.5xULN;Serum Glutamic-oxalacetic transaminase(SGOT), Aspartate transaminase(AST):>3xULN;Serum glutamic-pyruvic transaminase(SGPT), Alanine transaminase(ALT):>3xULN;Screening:AST/ALT >3xULN and Total Bilirubin >2xULN;Urea nitrogen:>2.5xULN; Creatinine, serum>1.5xbaseline assessment or change >0.3mg/dL since last visit;Glucose,blood (non-fasting):<55/>160mg/dL;Calcium:<7/>11.5mg/dL;Total protein: <5/>9g/dL; Albumin:<3g/dL;Sodium:<130/>150mmol/L;Potassium:<3/>5.5mmol/L; Uric acid,serum:>10mg/dL Males,>8mg/dL Females;Gamma Glutamyl Transpeptidase:>2.5xULN; Phosphorus,inorganic:<2.5/>5mg/dL;Lactate dehydrogenase:>3xULN;Urinalysis-Protein:>20mg/dL.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20	Clinically significant abnormality criteria for vital signs included Systolic blood pressure (BP): <100 millimeters of mercury (mmHg) or ≥140 mmHg or ≥140 mmHg and increase >10 from reference visit; Diastolic BP: <50 mmHg or ≥90 mmHg or ≥90 mmHg and increase >10 from reference visit; Pulse rate: <50 beats/minute or ≥120 beats/minute or ≥120 beats/minute and increase >15 from reference visit; Weight (kilograms) ≥10% change (increase and decrease) from baseline assessment; Body temperature: > 39-degree Celsius (°C ) or <35°C (oral, tympanic, axilla or forehead).	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20	Clinically significant abnormality criteria for ECG parameters included Heart rate: ≤50 or ≥100 beats/minute; PR Interval: ≥200 millisecond (msec); QRS Interval: ≥120 msec; QT: ≥480 msec; QT interval corrected using Bazett' s formula (QTcB): ≤ 500 msec; QT interval corrected using Fridericia's formula (QTcF): >500 msec; QT: increase from baseline ≥ 30; QTcB: increase from baseline < 60 msec; QTcF: increase from baseline ≥ 60.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20	PFTs include Spirometry which included forced vital capacity (FVC) % Predicted, considered as clinically significant abnormality when decrease is greater than10 percentage points from the reference visit.	From first dose of study drug through last follow up visit (up to 36 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Bioavailability (%F) of IgPro20	Relative bioavailability was calculated using Mixed Model Repeated Measures on Log-transformed Dose-normalized area under the curve to the end of the dosing period [AUC0-tau] following administration of the first dose of IgPro20 in the last week of dosing for Sequence A and / or Sequence B. Relative Bioavailability= (AUCtau IgPro20 (SC)/dose of IgPro20 (SC) / (AUCtau of IgPro10 (IV)/dose of IgPro10 (IV)).	Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20		Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20		Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Maximum Plasma Drug Concentration (Cmax) for IgPro20		Seq A-(Pre-injection [inj] at Weeks [Wks] 1,5,9,13,14; 24,48,72,96,168 hours [hrs] post 1st inj at Wk 14; 240 hrs post 1st inj at Wk 15), Seq B-(Pre-inj at Wks 17,21,25,29,30; 24,48,72,96,168 hrs post 1st inj at Wk 30; 240 hrs post 1st inj at Wk 31)
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A		Pre-injection at Weeks 5, 9, 13, and 14
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B		Pre-injection at Weeks 21, 25, 29, and 30
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10		Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10		Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Maximum Plasma Drug Concentration (Cmax) for IgPro10		Seq A and B respectively-Pre-infusion (inf) at Wks 17,21,25,29 and 1,5,9,13; 1 hour (hr) post 1st and 2nd inf, 168 hr post 1st inf at Wk 29,13; 264 and 336 hr post 1st inf at Wk 30, 14; 504 hr post 1st inf at Wk 31,15; 672 hr post 1st inf at Wk 32,16
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A		Pre-infusion at Weeks 21, 25 and 29
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B		Pre-infusion at Weeks 5, 9 and 13
Number of Participants With at Least One AE for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One AE for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One TEAE for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One TEAE for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One SAE for IgPro10	An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One SAE for IgPro10	An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One AESI for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One AESI for IgPro10	AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With AEs Categorized as ISRs for IgPro10	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.	From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With AEs Categorized as ISRs for IgPro10	ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10	Abnormality criteria:Hematology-Hemoglobin:<10 g/dL;Platelet count:<75x10^9/L or >500x10^9/L;White Blood Cell Count:<3x10^9/L or >16x10^9/L;Neutrophils:absolute <1.5x10^9/L,differential <40%;Lymphocytes:absolute <0.8x10^9/L,differential <10 or >50%; Biochemistry-Bilirubin:>1.5xupper limit of normal (ULN);Alkaline phosphatase:>2.5xULN;Serum Glutamic-oxalacetic transaminase(SGOT), Aspartate transaminase(AST):>3xULN;Serum glutamic-pyruvic transaminase(SGPT), Alanine transaminase(ALT):>3xULN;Screening:AST/ALT >3xULN and Total Bilirubin >2xULN;Urea nitrogen:>2.5xULN; Creatinine, serum>1.5xbaseline assessment or change >0.3mg/dL since last visit;Glucose,blood (non-fasting):<55/>160mg/dL;Calcium:<7/>11.5mg/dL;Total protein: <5/>9g/dL; Albumin:<3g/dL;Sodium:<130/>150mmol/L;Potassium:<3/>5.5mmol/L; Uric acid,serum:>10mg/dL Males,>8mg/dL Females;Gamma Glutamyl Transpeptidase:>2.5xULN; Phosphorus,inorganic:<2.5/>5mg/dL;Lactate dehydrogenase:>3xULN;Urinalysis-Protein:>20mg/dL.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10	Clinically significant abnormality criteria for vital signs included Systolic blood pressure (BP): <100 millimeters of mercury (mmHg) or ≥140 mmHg or ≥140 mmHg and increase >10 from reference visit; Diastolic BP: <50 mmHg or ≥90 mmHg or ≥90 mmHg and increase >10 from reference visit; Pulse rate: <50 beats/minute or ≥120 beats/minute or ≥120 beats/minute and increase >15 from reference visit; Weight (kilograms) ≥10% change (increase and decrease) from baseline assessment; Body temperature: > 39-degree Celsius (°C ) or <35°C (oral, tympanic, axilla or forehead).	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10	Clinically significant abnormality criteria for ECG parameters included Heart rate: ≤50 or ≥100 beats/minute; PR Interval: ≥200 millisecond (msec); QRS Interval: ≥120 msec; QT: ≥480 msec; QT interval corrected using Bazett' s formula (QTcB): ≤ 500 msec; QT interval corrected using Fridericia's formula (QTcF): >500 msec; QT: increase from baseline ≥ 30; QTcB: increase from baseline < 60 msec; QTcF: increase from baseline ≥ 60.	From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10	PFTs include Spirometry which included forced vital capacity (FVC) % Predicted, considered as clinically significant abnormality when decrease is greater than10 percentage points from the reference visit.	From first dose of study drug through last follow up visit (up to 36 weeks)

Other Outcome Measures

Outcome Measure	Time Frame
Rate of ISRs Per Participant for IgPro20	From first dose of study drug through last follow up visit (up to 36 weeks)

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2019
• Primary Completion (Actual): May 17, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: October 21, 2019
• First Submitted That Met QC Criteria: October 22, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): February 5, 2024
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: scleroderma
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: IgPro20_2001; 2018-003149-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

CSL will consider requests to share Individual Patient Data (IPD) from systematic review groups or bona-fide researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Time Frame: IPD requests may be submitted to CSL no earlier than 12 months after publication of the results of this study via an article made available on a public website.

IPD Sharing Access Criteria

Requests may only be made by systematic review groups or bona-fide researchers whose proposed use of the IPD is non-commercial in nature and has been approved by an internal review committee.

An IPD request will not be considered by CSL unless the proposed research question seeks to answer a significant and unknown medical science or patient care question as determined by CSL's internal review committee.

The requesting party must execute an appropriate data sharing agreement before IPD will be made available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No