A Multicenter, Randomized, Open-label, Crossover, Phase 2 Study to Evaluate the Safety and Pharmacokinetics of IgPro20 (Subcutaneous Immunoglobulin, Hizentra®) and IgPro10 (Intravenous Immunoglobulin, Privigen®) in Adults With Systemic Sclerosis (SSc)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- CSL Behring
- 入组人数
- 27
- 试验地点
- 18
- 主要终点
- Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Number of Participants With at Least One Serious Adverse Event (SAE) for IgPro20
时间窗: 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
时间窗: 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 AEs Categorized as ISRs for IgPro20
时间窗: 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 Electrocardiogram (ECG) Parameters for IgPro20
时间窗: 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.
Time to Onset of ISRs for IgPro20
时间窗: 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.
Number of Participants With at Least One Adverse Event (AE) for IgPro20
时间窗: 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
时间窗: 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.
Rate of ISRs Per Infusion for IgPro20
时间窗: 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'
Duration of ISRs for IgPro20
时间窗: 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
时间窗: 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 Abnormalities in Pulmonary Function Tests (PFTs) for IgPro20
时间窗: 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 at Least One AESI for IgPro20
时间窗: 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
时间窗: 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 at Least One Treatment-Emergent Adverse Event (TEAE) for IgPro20
时间窗: 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
时间窗: 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.
Percentage of Participants With at Least One SAE for IgPro20
时间窗: 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 Clinically Significant Changes in Vital Signs for IgPro20
时间窗: 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).
次要结局
- 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))
- 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))
- 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 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)
- 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 AESI for IgPro10(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(From first dose of study drug through last follow up visit (up to 36 weeks))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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)
- Minimum Plasma Drug Concentration (Ctrough) for IgPro10 in Sequence A(Pre-infusion at Weeks 21, 25 and 29)
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))