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

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

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)

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Placebo; Drug: Abatacept; Drug: Abatacept

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Liu MF, Wang CR, Lin LC, Wu CR. CTLA-4 gene polymorphism in promoter and exon-1 regions in Chinese patients with systemic lupus erythematosus. Lupus. 2001;10(9):647-9. doi: 10.1191/096120301682430249.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 24, 2008
• First Submitted That Met QC Criteria: June 24, 2008
• First Posted (Estimate): June 26, 2008

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 23, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-217