This is a prospective, multicenter, randomized, open-label, crossover study to investigate the safety, tolerability, and pharmacokinetics of IgPro20 in participants with diffuse cutaneous systemic sclerosis (dcSSc). The pharmacokinetic study aims to evaluate the relative bioavailability of IgPro20, and characterize pharmacokinetics of IgPro20 and IgPro10, respectively, in participants with dcSSc. Safety, tolerability, and pharmacokinetics of IgPro10 will also be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Charité Universitätsmedizin Berlin
Berlin, Germany
Uniklinik Köln, innere Medizin
Cologne, Germany
ASST Spedali Civili di Brescia
Brescia, Italy
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)
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)
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)
Percentage of Participants With at Least One TEAE for IgPro20
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Azienda Ospedaliera Gaetano Pini
Milan, Italy
Uniwersytecki Szpital Kliniczny W Bialymstoku
Bialystok, Poland
Szpital Kliniczny Jezus
Warsaw, Poland
Narodowy Instytut Geriatrii
Warsaw, Poland
The Royal Free Hospital
London, United Kingdom
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence A
Time frame: Pre-injection at Weeks 5, 9, 13, and 14
Minimum Plasma Drug Concentration (Ctrough) for IgPro20 in Sequence B
Time frame: 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
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
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
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
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A
Time frame: Pre-infusion at Weeks 21, 25 and 29
Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence B
Time frame: Pre-infusion at Weeks 5, 9 and 13
Number of Participants With at Least One AE for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One AE for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One TEAE for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One TEAE for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. TEAEs are defined as AEs reported at or after the start of the first infusion in the study.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One SAE for IgPro10
An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One SAE for IgPro10
An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With at Least One AESI for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With at Least One AESI for IgPro10
AE is any untoward medical occurrence in a patient or clinical investigation participant administered with a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can be any unfavorable and unintended sign (including an abnormal, clinically significant laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An AESI is an AE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor is appropriate.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With AEs Categorized as ISRs for IgPro10
ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Percentage of Participants With AEs Categorized as ISRs for IgPro10
ISRs included all events reported within the MedDRA high-level terms 'Administration site reactions', 'Infusion site reactions', or 'Injection site reactions'.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in Laboratory Tests for IgPro10
Abnormality criteria:Hematology-Hemoglobin:\<10 g/dL;Platelet count:\<75x10\^9/L or \>500x10\^9/L;White Blood Cell Count:\<3x10\^9/L or \>16x10\^9/L;Neutrophils:absolute \<1.5x10\^9/L,differential \<40%;Lymphocytes:absolute \<0.8x10\^9/L,differential \<10 or \>50%; Biochemistry-Bilirubin:\>1.5xupper limit of normal (ULN);Alkaline phosphatase:\>2.5xULN;Serum Glutamic-oxalacetic transaminase(SGOT), Aspartate transaminase(AST):\>3xULN;Serum glutamic-pyruvic transaminase(SGPT), Alanine transaminase(ALT):\>3xULN;Screening:AST/ALT \>3xULN and Total Bilirubin \>2xULN;Urea nitrogen:\>2.5xULN; Creatinine, serum\>1.5xbaseline assessment or change \>0.3mg/dL since last visit;Glucose,blood (non-fasting):\<55/\>160mg/dL;Calcium:\<7/\>11.5mg/dL;Total protein: \<5/\>9g/dL; Albumin:\<3g/dL;Sodium:\<130/\>150mmol/L;Potassium:\<3/\>5.5mmol/L; Uric acid,serum:\>10mg/dL Males,\>8mg/dL Females;Gamma Glutamyl Transpeptidase:\>2.5xULN; Phosphorus,inorganic:\<2.5/\>5mg/dL;Lactate dehydrogenase:\>3xULN;Urinalysis-Protein:\>20mg/dL.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Changes in Vital Signs for IgPro10
Clinically significant abnormality criteria for vital signs included Systolic blood pressure (BP): \<100 millimeters of mercury (mmHg) or ≥140 mmHg or ≥140 mmHg and increase \>10 from reference visit; Diastolic BP: \<50 mmHg or ≥90 mmHg or ≥90 mmHg and increase \>10 from reference visit; Pulse rate: \<50 beats/minute or ≥120 beats/minute or ≥120 beats/minute and increase \>15 from reference visit; Weight (kilograms) ≥10% change (increase and decrease) from baseline assessment; Body temperature: \> 39-degree Celsius (°C ) or \<35°C (oral, tympanic, axilla or forehead).
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in ECG Parameters for IgPro10
Clinically significant abnormality criteria for ECG parameters included Heart rate: ≤50 or ≥100 beats/minute; PR Interval: ≥200 millisecond (msec); QRS Interval: ≥120 msec; QT: ≥480 msec; QT interval corrected using Bazett' s formula (QTcB): ≤ 500 msec; QT interval corrected using Fridericia's formula (QTcF): \>500 msec; QT: increase from baseline ≥ 30; QTcB: increase from baseline \< 60 msec; QTcF: increase from baseline ≥ 60.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)
Number of Participants With Clinically Significant Abnormalities in PFTs for IgPro10
PFTs include Spirometry which included forced vital capacity (FVC) % Predicted, considered as clinically significant abnormality when decrease is greater than10 percentage points from the reference visit.
Time frame: From first dose of study drug through last follow up visit (up to 36 weeks)