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

Diffuse Cutaneous Systemic Sclerosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04137224
• Other study ID #: IgPro20_2001
• Secondary ID: 2018-003149-41
• Status: Completed
• Phase: Phase 2
• Start date: September 19, 2019
• Est. completion date: May 17, 2022

Study information

• Verified date: May 2023
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 17, 2022
• Est. primary completion date: May 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Cutaneous Systemic Sclerosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Biological:
• IgPro20
Human normal immunoglobulin for subcutaneous administration
• IgPro10
Human normal immunoglobulin for intravenous administration

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Uniklinik Köln, innere Medizin	Köln
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedaliera Gaetano Pini	Milano
Poland	Uniwersytecki Szpital Kliniczny W Bialymstoku	Bialystok
Poland	Narodowy Instytut Geriatrii	Warsaw
Poland	Szpital Kliniczny Jezus	Warsaw
United Kingdom	The Royal Free Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

Australia,  Germany,  Italy,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of ISRs Per Participant for IgPro20		From first dose of study drug through last follow up visit (up to 36 weeks)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A		Pre-injection at Weeks 5, 9, 13, and 14
Secondary	Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B		Pre-injection at Weeks 21, 25, 29, and 30
Secondary	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
Secondary	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
Secondary	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
Secondary	Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A		Pre-infusion at Weeks 21, 25 and 29
Secondary	Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B		Pre-infusion at Weeks 5, 9 and 13
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)