Back to resultsPhase I Study in China - Tolerability of a Single Dose of Abatacept 30 mg/kg
Primary Purpose
Lupus Nephritis
Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Placebo
Abatacept
Abatacept
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Nephritis
Eligibility Criteria
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
Sites / Locations
- Local Institution
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Active Comparator
Other
Arm Label
Placebo
Abatacept, 30 mg/kg
Abatacept, 10 mg/kg
Arm Description
Open-label long-term extension phase
Outcomes
Primary Outcome Measures
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.
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).
Short-term Period: MeanSystolic and Diastolic Blood Pressure
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Short-term Period: Mean Heart Rate
Vital signs measurements are summarized without regard to position (sitting, standing, supine).
Short-term Period: Mean Respirations Rate
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Short-term Period: Mean Temperature
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities
Laboratory tests consisted of complete blood count, chemistry, and urinalysis.
Secondary Outcome Measures
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.
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.
Maximum (Cmax) Plasma Concentration of Abatacept
Cmax is a drug's maximum, or peak, concentration observed after its administration.
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
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.
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:
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00705367
Brief Title
Phase I Study in China - Tolerability of a Single Dose of Abatacept 30 mg/kg
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
January 2009 (Actual)
Study Completion Date
July 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Abatacept, 30 mg/kg
Arm Type
Active Comparator
Arm Title
Abatacept, 10 mg/kg
Arm Type
Other
Arm Description
Open-label long-term extension phase
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Infusion, Intravenous, single dose, Day 1
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Orencia, BMS-188667
Intervention Description
Infusion, Intravenous, 30mg/kg, single dose, Day 1
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Orencia, BMS-188667
Intervention Description
Infusion, intravenous, 10 mg/kg, administered on Days 15 and 29 followed by doses every 4 weeks until the end of the study
Primary Outcome Measure Information:
Title
Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs
Description
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.
Time Frame
From Day 1 of double-blind period to 1st dose of long-term period
Title
Short-term Period: Number of Adverse Events (AEs) Related to Study Drug
Description
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).
Time Frame
From Day 1 of double-blind period to 1st dose of long-term period
Title
Short-term Period: MeanSystolic and Diastolic Blood Pressure
Description
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time Frame
Day 1 predose and postdose and Day 2
Title
Short-term Period: Mean Heart Rate
Description
Vital signs measurements are summarized without regard to position (sitting, standing, supine).
Time Frame
Day 1 predose and postdose and Day 2
Title
Short-term Period: Mean Respirations Rate
Description
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time Frame
Day 1 predose and postdose and Day 2
Title
Short-term Period: Mean Temperature
Description
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time Frame
Day 1 predose and postdose and Day 2
Title
Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities
Description
Laboratory tests consisted of complete blood count, chemistry, and urinalysis.
Time Frame
Screening and Days 1 and 2
Secondary Outcome Measure Information:
Title
Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs
Description
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.
Time Frame
Days 15 to 56 days post last dose of the long-term period
Title
Minimum (Cmin) Plasma Concentration of Abatacept
Description
Cmin is the minimum, or trough, concentration of a drug observed after its administration and just prior to the administration of a subsequent dose.
Time Frame
Days 15, 29, 85, 169, 253 and 337
Title
Maximum (Cmax) Plasma Concentration of Abatacept
Description
Cmax is a drug's maximum, or peak, concentration observed after its administration.
Time Frame
Postdosing Day 1
Title
Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests
Description
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
Time Frame
Days 15 to 56 days post last dose of the long-term period
Title
Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued)
Description
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.
Time Frame
Days 15 to 56 days post last dose of the long-term period
Title
Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued)
Description
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:
Time Frame
Days 15 to 56 days post last dose of the long-term period
Title
Long-term Period: Number of Participants With Abatacept-specific Antibodies
Description
Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability.
Time Frame
Day15 to 56 days post last dose of the long-term period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Local Institution
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200001
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
11678454
Citation
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.
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Phase I Study in China - Tolerability of a Single Dose of Abatacept 30 mg/kg
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