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

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.

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.

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.

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.

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.

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.

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.

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.

ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

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'

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.

ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

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.

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).

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.

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.

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)).

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.

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.

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.

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.

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.

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.

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.

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.

ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.

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.

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).

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.

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.