Phase I Study in China - Tolerability of a Single Dose of Abatacept 30 mg/kg

Study Overview
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Brief Summary
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The purpose of this study is to determine whether abatacept at a dose 30 mg/kg via intravenous infusion is safe and well tolerated in the treatment of lupus nephritis in mainland Chinese subjects with systemic lupus erythematosus (SLE)

Official Title
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A Single Center, Randomized, Placebo-Controlled, Double Blind, Parallel Group Study to Evaluate the Tolerability of a Single Dose of Abatacept 30 mg/kg Via Intravenous Infusion in Chinese SLE Subjects With Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Placebo
* Drug: Abatacept
* Drug: Abatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, at least 18 years of age, with a diagnosis of systemic lupus erythematosus (SLE) and with lupus nephritis currently stable for the last 3 months without change in treatment for lupus nephritis Stable renal disease No flaring of other organ systems in a minimum of the last 3 months Exclusion Criteria: Unstable lupus nephritis and serum creatinine >3 mg/dL Progressive renal failure, end stage renal disease, or renal transplant requiring continuous dialysis Severe unstable, refractory, or progressive SLE History of cancer Participants at risk for tuberculosis Autoimmune disease other than SLE as main diagnosis Human immunodeficiency virus or herpes zoster infection Hepatitis-B surface antigen-positive or hepatitis C antibody-positive participants

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Infusion, Intravenous, single dose, Day 1<br>|
| Active Comparator: Abatacept, 30 mg/kg<br> | Drug: Abatacept<br>* Infusion, Intravenous, 30mg/kg, single dose, Day 1<br>* Other names: BMS-188667;|
| Other: Abatacept, 10 mg/kg<br>Open-label long-term extension phase | Drug: Abatacept<br>* Infusion, intravenous, 10 mg/kg, administered on Days 15 and 29 followed by doses every 4 weeks until the end of the study<br>* Other names: BMS-188667;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. | From Day 1 of double-blind period to 1st dose of long-term period | 
| Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. Intensity = mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening/disabling (grade 4). | From Day 1 of double-blind period to 1st dose of long-term period | 
| Short-term Period: MeanSystolic and Diastolic Blood Pressure | Vital sign measurements are summarized without regard to position (sitting, standing, supine). | Day 1 predose and postdose and Day 2 | 
| Short-term Period: Mean Heart Rate | Vital signs measurements are summarized without regard to position (sitting, standing, supine). | Day 1 predose and postdose and Day 2 | 
| Short-term Period: Mean Respirations Rate | Vital sign measurements are summarized without regard to position (sitting, standing, supine). | Day 1 predose and postdose and Day 2 | 
| Short-term Period: Mean Temperature | Vital sign measurements are summarized without regard to position (sitting, standing, supine). | Day 1 predose and postdose and Day 2 | 
| Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | Laboratory tests consisted of complete blood count, chemistry, and urinalysis. | Screening and Days 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event. | Days 15 to 56 days post last dose of the long-term period | 
| Minimum (Cmin) Plasma Concentration of Abatacept | Cmin is the minimum, or trough, concentration of a drug observed after its administration and just prior to the administration of a subsequent dose. | Days 15, 29, 85, 169, 253 and 337 | 
| Maximum (Cmax) Plasma Concentration of Abatacept | Cmax is a drug's maximum, or peak, concentration observed after its administration. | Postdosing Day 1 | 
| Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. hemoglobin (g/dL): >3g/dL drop from preRX; hematocrit (%): <0.75*preRX; erythrocytes (*10^6 c/uL): <0.75*preRX; platelet count (*10^9 c/L): <0.67*LLN or >1.5*ULN, or <100,000/mm^3 or if preRX<LLN, use <0.5*preRX and <100,000/mm^3; leukocytes (*10^3 c/uL): <0.75*LLN, >1.25*ULN, <0.8*preRX if preRX <LLN or >1.2*preRX if preRX >ULN; >ULN if preRX <LLN, <LLN if >ULN preRX; neutrophils+bands (*10^3 c/uL): if value <1.00*10^3 c/uL; lymphocytes (*10^3 c/uL): if value <0.750*10^3 c/uL or if value >7.50*10^3 c/uL; monocytes (*10^3 c/uL): if value >2000/mm^3; basophils (*10^3 c/uL): if value >400/mm^3; eosinophils (*10^3 c/uL): if value> 0.750*10^3 c/uL | Days 15 to 56 days post last dose of the long-term period | 
| Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | preRX=pretreatment; LLN=lower limit of normal; ULN=upper limit of normal. Glucose (mg/dL): <65 or >220. Glucose, fasting(mg/dL): <0.8*LLN or >1.5* ULN; if preRX<LLN, use <0.8*preRX or >ULN; if preRX>ULN, use >2.0*preRX or <LLN. Protein, total (g/dL): <0.9*LLN or >1.1*ULN; if preRX<LLN, use 0.9*preRX or >ULN if preRX >ULN, use 1.1*preRX or <LLN. Albumin (g/dL): <0.9*LLN, or if preRX<LLN use <0.75*preRX. Uric acid (mg/dL): >1.5*ULN; if preRX>ULN use >2*preRX. Protein, urine: if missing preRX, use>=2; if >=4; if preRX=0 or 0.5, use >=2; if preRX=1, use >=3, or if preRX=2 or 3, use >= 4. Glucose, urine: if preRX missing, use >=2; if >=4, or if preRX=0 or 0.5 use >=2,or if preRX=1, use >=3, or if preRX=2 or 3 use >=4. Blood, urine: if preRX missing, use>= 2, or if >=4, or if preRX=0 or 0.5, use >=2, or if preRX=1, use >=3; if preRX=2 or 3 use >=4. WBC, urine (hpf): if missing preRX, use>= 2, or if >= 4, or if preRX =0 or 0.5 use >=2, or if preRX=1 use >=3, or if preRX=2 or 3 use >=4. | Days 15 to 56 days post last dose of the long-term period | 
| Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | ULN=upper limit of normal; preRX=pretreatment: ALP (U/L): >2*ULN, or if preRX>ULN, use >3*preRX; AST (U/L): >3*ULN, or if preRX>ULN, use >4*preRX; ALT (U/L): >3X*ULN, or if preRX>ULN, use >4*preRX; GGT (/L): >*ULN, or if preRX>ULN, use >3*preRX; bilirubin (mg/dL): >2*ULN, or if preRX>ULN, use >4*preRX; BUN (mg/dL):>2*preRX; sodium: <.95*LLN, >1.05*ULN, <.95* preRX if <LLN preRX, >1.05*preRX if >ULN preRX; >ULN if <LLN preRX, <LLN if >ULN preRX; potassium: chloride: calcium: phosphorous: | Days 15 to 56 days post last dose of the long-term period | 
| Long-term Period: Number of Participants With Abatacept-specific Antibodies | Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability. | Day15 to 56 days post last dose of the long-term period |