Diffuse Cutaneous Systemic Sclerosis
Conditions
Keywords
scleroderma
Brief 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.
Interventions
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One Adverse Event (AE) for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One AE for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One TEAE for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One SAE for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20 | From first dose of study drug through last follow-up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One AESI for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. |
| Percentage of Participants With AEs Categorized as ISRs for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. |
| Rate of ISRs Per Infusion for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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' |
| Time to Onset of ISRs for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Duration of ISRs for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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). |
| Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One SAE for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One SAE for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One AESI for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With AEs Categorized as ISRs for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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). |
| Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Percentage of Participants With AEs Categorized as ISRs for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'. |
| Relative Bioavailability (%F) of 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) | 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)). |
| 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 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One AE for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One TEAE for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Percentage of Participants With at Least One TEAE for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
| Number of Participants With at Least One AESI for IgPro10 | From first dose of study drug through last follow up visit (up to 36 weeks) | 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. |
Other
| 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) |
Countries
Australia, Germany, Italy, Poland, United Kingdom
Participant flow
Recruitment details
Participants were enrolled at study centers in Australia, Germany, Italy, Poland, and the United Kingdom from 19 September 2019 to 17 May 2022.
Pre-assignment details
A total of 30 participants were screened, of which 27 participants were enrolled and randomized to Sequence A or Sequence B in this study.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A (IgPro20/IgPro10) Participants received IgPro20 of a total dose of 0.5 g/kg over 2 sessions per week as an 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 IV infusion for up to 16 weeks in Treatment Period 2. | 13 |
| 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. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 (Week 1 to Week 16) | Adverse Event | 1 | 0 |
| Treatment Period 1 (Week 1 to Week 16) | Withdrawal by Subject | 0 | 1 |
| Treatment Period 2 (Week 17 to Week 32) | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Sequence B (IgPro10/IgPro20) | Sequence A (IgPro20/IgPro10) |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 12.5 | 47.4 years STANDARD_DEVIATION 12.91 | 51.4 years STANDARD_DEVIATION 12.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 14 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 26 Participants | 13 Participants | 13 Participants |
| Region of Enrollment Australia | 2 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Germany | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Italy | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Poland | 17 Participants | 8 Participants | 9 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 18 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 8 / 13 | 5 / 13 | 8 / 14 | 6 / 13 |
| serious Total, serious adverse events | 2 / 13 | 1 / 13 | 1 / 14 | 3 / 13 |
Outcome results
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'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 and with ISRs were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence A: IgPro20 | Duration of ISRs for IgPro20 | 162.0 minutes |
| Sequence B: IgPro20 | Duration of ISRs for IgPro20 | 220.0 minutes |
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'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20 | 2 Participants |
| Sequence B: IgPro20 | Number of Participants With AEs Categorized as Infusion Site Reactions (ISRs) for IgPro20 | 3 Participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One Adverse Event (AE) for IgPro20 | 9 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One Adverse Event (AE) for IgPro20 | 9 Participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One Adverse Event of Special Interest (AESI) for IgPro20 | 1 Participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20 | 2 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20 | 3 Participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20 | 9 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20 | 9 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters for IgPro20 | 1 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro20 | 0 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20 | 0 Participants |
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).
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Changes in Vital Signs for IgPro20 | 0 Participants |
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'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With AEs Categorized as ISRs for IgPro20 | 15.4 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With AEs Categorized as ISRs for IgPro20 | 23.1 percentage of participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One AE for IgPro20 | 69.2 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One AE for IgPro20 | 69.2 percentage of participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One AESI for IgPro20 | 0 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One AESI for IgPro20 | 7.7 percentage of participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One SAE for IgPro20 | 15.4 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One SAE for IgPro20 | 23.1 percentage of participants |
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.
Time frame: From first dose of study drug through last follow-up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One TEAE for IgPro20 | 69.2 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One TEAE for IgPro20 | 69.2 percentage of participants |
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'
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Rate of ISRs Per Infusion for IgPro20 | 0.0057 ISRs per infusion |
| Sequence B: IgPro20 | Rate of ISRs Per Infusion for IgPro20 | 0.0360 ISRs per infusion |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 and with ISRs were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence A: IgPro20 | Time to Onset of ISRs for IgPro20 | 2.0 days |
| Sequence B: IgPro20 | Time to Onset of ISRs for IgPro20 | 15.0 days |
Secondary
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10
Time frame: 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
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro10 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10 | 16942.66 h*g/L |
| Sequence B: IgPro20 | Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro10 | 17672.03 h*g/L |
Secondary
Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20
Time frame: 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)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro20 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20 | 3835.68 hours*grams per liter (h*g/L) |
| Sequence B: IgPro20 | Area Under the Concentration Curve to the End of the Dosing Period (AUC0-tau) for IgPro20 | 3581.08 hours*grams per liter (h*g/L) |
Secondary
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10
Time frame: 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
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro10 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10 | 16520.48 h*g/L |
| Sequence B: IgPro20 | Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro10 | 17349.72 h*g/L |
Secondary
Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20
Time frame: 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)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro20 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20 | 5361.61 h*g/L |
| Sequence B: IgPro20 | Area Under the Concentration Curve up to the Last Measurable Concentration (AUC0-last) for IgPro20 | 4898.02 h*g/L |
Secondary
Maximum Plasma Drug Concentration (Cmax) for IgPro10
Time frame: 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
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro10 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Maximum Plasma Drug Concentration (Cmax) for IgPro10 | 47.142 g/L |
| Sequence B: IgPro20 | Maximum Plasma Drug Concentration (Cmax) for IgPro10 | 44.996 g/L |
Secondary
Maximum Plasma Drug Concentration (Cmax) for IgPro20
Time frame: 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)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro20 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Maximum Plasma Drug Concentration (Cmax) for IgPro20 | 24.237 g/L |
| Sequence B: IgPro20 | Maximum Plasma Drug Concentration (Cmax) for IgPro20 | 23.203 g/L |
Secondary
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A
Time frame: Pre-infusion at Weeks 21, 25 and 29
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A | Week 21 | 16.123 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A | Week 25 | 17.497 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A | Week 29 | 16.838 g/L |
Secondary
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B
Time frame: Pre-infusion at Weeks 5, 9 and 13
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro10 and with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B | Week 5 | 17.104 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B | Week 9 | 17.744 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B | Week 13 | 17.113 g/L |
Secondary
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A
Time frame: Pre-injection at Weeks 5, 9, 13, and 14
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro20 were analyzed. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A | Week 5 | 22.046 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A | Week 9 | 21.950 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A | Week 13 | 22.354 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A | Week 14 | 21.814 g/L |
Secondary
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B
Time frame: Pre-injection at Weeks 21, 25, 29, and 30
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro20 and with data available for outcome measure analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B | Week 21 | 20.427 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B | Week 25 | 21.603 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B | Week 29 | 21.903 g/L |
| Sequence A: IgPro20 | Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B | Week 30 | 20.497 g/L |
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'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With AEs Categorized as ISRs for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With AEs Categorized as ISRs for IgPro10 | 0 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One AE for IgPro10 | 5 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One AE for IgPro10 | 8 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One AESI for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One AESI for IgPro10 | 0 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One SAE for IgPro10 | 1 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One SAE for IgPro10 | 1 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With at Least One TEAE for IgPro10 | 5 Participants |
| Sequence B: IgPro20 | Number of Participants With at Least One TEAE for IgPro10 | 8 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10 | 0 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10 | 0 Participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10 | 0 Participants |
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).
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence A: IgPro20 | Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10 | 0 Participants |
| Sequence B: IgPro20 | Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10 | 0 Participants |
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'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With AEs Categorized as ISRs for IgPro10 | 0 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With AEs Categorized as ISRs for IgPro10 | 0 percentage of participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One AE for IgPro10 | 38.5 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One AE for IgPro10 | 57.1 percentage of participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One AESI for IgPro10 | 0 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One AESI for IgPro10 | 0 percentage of participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One SAE for IgPro10 | 7.7 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One SAE for IgPro10 | 7.1 percentage of participants |
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.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. Participants who received IgPro10 were analyzed. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sequence A: IgPro20 | Percentage of Participants With at Least One TEAE for IgPro10 | 38.5 percentage of participants |
| Sequence B: IgPro20 | Percentage of Participants With at Least One TEAE for IgPro10 | 57.1 percentage of participants |
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)).
Time frame: 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)
Population: Safety analysis set included all participants who received at least 1 infusion of IgPro20 or IgPro10. 'Overall number of participants analyzed' indicates the number of participants who received IgPro20 and with data available for outcome measure analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sequence A: IgPro20 | Relative Bioavailability (%F) of IgPro20 | 0.831 percentage bioavailability |
| Sequence B: IgPro20 | Relative Bioavailability (%F) of IgPro20 | 0.698 percentage bioavailability |
Other Pre-specified
Rate of ISRs Per Participant for IgPro20
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)