Lupus Nephritis
Conditions
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)
Interventions
DRUGPlacebo
Infusion, Intravenous, single dose, Day 1
DRUGAbatacept
Infusion, Intravenous, 30mg/kg, single dose, Day 1
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | Screening and Days 1 and 2 | Laboratory tests consisted of complete blood count, chemistry, and urinalysis. |
| Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | From Day 1 of double-blind period to 1st dose of long-term period | 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 | From Day 1 of double-blind period to 1st dose of long-term period | 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 | Day 1 predose and postdose and Day 2 | Vital sign measurements are summarized without regard to position (sitting, standing, supine). |
| Short-term Period: Mean Heart Rate | Day 1 predose and postdose and Day 2 | Vital signs measurements are summarized without regard to position (sitting, standing, supine). |
| Short-term Period: Mean Respirations Rate | Day 1 predose and postdose and Day 2 | Vital sign measurements are summarized without regard to position (sitting, standing, supine). |
| Short-term Period: Mean Temperature | Day 1 predose and postdose and Day 2 | Vital sign measurements are summarized without regard to position (sitting, standing, supine). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Period: Number of Participants With Abatacept-specific Antibodies | Day15 to 56 days post last dose of the long-term period | Antiabatacept antibodies in human serum were assayed using a validated electrochemiluminescent immunoassay during the period of known analyte stability. |
| Minimum (Cmin) Plasma Concentration of Abatacept | Days 15, 29, 85, 169, 253 and 337 | 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 | Postdosing Day 1 | 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 | Days 15 to 56 days post last dose of the long-term period | 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) | Days 15 to 56 days post last dose of the long-term period | 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 Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | Days 15 to 56 days post last dose of the long-term period | 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. |
Countries
China
Participant flow
Pre-assignment details
Thirteen (13) participants were enrolled in the short-term period of the study. Four (4/13, 30.8%) of these participants were not randomized: 3 (23.1%) no longer met study criteria after screening, and 1 (7.7%) withdrew consent. All 9 participants who completed the short-term period entered the long-term period.
Participants by arm
| Arm | Count |
|---|---|
| Abatacept (30 mg/kg) Infusion, Intravenous, 30 mg/kg, single dose, 24 hours | 6 |
| Placebo Infusion, Intravenous, single dose, 24 hours | 3 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-term Extension Period | Administrative reason by sponsor | 3 | 0 |
| Long-term Extension Period | Adverse Event | 2 | 0 |
| Long-term Extension Period | Lack of Efficacy | 1 | 0 |
| Long-term Extension Period | No longer met study criteria | 1 | 0 |
| Long-term Extension Period | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Abatacept (30 mg/kg) | Total |
|---|---|---|---|
| Age Continuous | 41.33 years STANDARD_DEVIATION 8.33 | 32.50 years STANDARD_DEVIATION 8.76 | 35.44 years STANDARD_DEVIATION 9.21 |
| Duration of Lupus Nephritis | 85.26 months STANDARD_DEVIATION 65.03 | 41.23 months STANDARD_DEVIATION 32.9 | 55.90 months STANDARD_DEVIATION 47.1 |
| Duration of Systemic Lupus Erythematosus (SLE) | 11.11 years STANDARD_DEVIATION 3.18 | 7.20 years STANDARD_DEVIATION 5.06 | 8.50 years STANDARD_DEVIATION 4.73 |
| Region of Enrollment China | 3 participants | 6 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
| Weight | 63.67 kg STANDARD_DEVIATION 4.04 | 58.83 kg STANDARD_DEVIATION 10.38 | 60.44 kg STANDARD_DEVIATION 8.79 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 1 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 |
Outcome results
Primary
Short-term Period: Mean Heart Rate
Vital signs measurements are summarized without regard to position (sitting, standing, supine).
Time frame: Day 1 predose and postdose and Day 2
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Mean Heart Rate | Day 1 predose | 77.0 beats per minute | Standard Deviation 8.49 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Heart Rate | Day 1 postdose | 81.2 beats per minute | Standard Deviation 4.83 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Heart Rate | Day 2 | 83.5 beats per minute | Standard Deviation 4.46 |
| Placebo | Short-term Period: Mean Heart Rate | Day 1 predose | 81.0 beats per minute | Standard Deviation 10.15 |
| Placebo | Short-term Period: Mean Heart Rate | Day 1 postdose | 87.7 beats per minute | Standard Deviation 19.6 |
| Placebo | Short-term Period: Mean Heart Rate | Day 2 | 84.0 beats per minute | Standard Deviation 5.29 |
Primary
Short-term Period: Mean Respirations Rate
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time frame: Day 1 predose and postdose and Day 2
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Mean Respirations Rate | Day 1 predose | 17.7 Respirations per minute | Standard Deviation 2.07 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Respirations Rate | Day 1 postdose | 18.7 Respirations per minute | Standard Deviation 1.63 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Respirations Rate | Day 2 | 14.0 Respirations per minute | Standard Deviation 3.35 |
| Placebo | Short-term Period: Mean Respirations Rate | Day 1 predose | 19.7 Respirations per minute | Standard Deviation 2.08 |
| Placebo | Short-term Period: Mean Respirations Rate | Day 1 postdose | 20.3 Respirations per minute | Standard Deviation 2.52 |
| Placebo | Short-term Period: Mean Respirations Rate | Day 2 | 17.3 Respirations per minute | Standard Deviation 1.15 |
Primary
Short-term Period: MeanSystolic and Diastolic Blood Pressure
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time frame: Day 1 predose and postdose and Day 2
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 1 predose | 129.0 mm Hg | Standard Deviation 20.47 |
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 1 postdose | 125.8 mm Hg | Standard Deviation 19.58 |
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 1 predose | 84.2 mm Hg | Standard Deviation 8.86 |
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 1 postdose | 82.7 mm Hg | Standard Deviation 9.58 |
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 2 | 127.5 mm Hg | Standard Deviation 13.69 |
| Abatacept (30 mg/kg) | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 2 | 79.5 mm Hg | Standard Deviation 8.69 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 2 | 126.7 mm Hg | Standard Deviation 11.55 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 1 predose | 133.0 mm Hg | Standard Deviation 8.89 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 1 postdose | 82.7 mm Hg | Standard Deviation 14.22 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Systolic blood pressure: Day 1 postdose | 131.7 mm Hg | Standard Deviation 9.29 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 2 | 78.3 mm Hg | Standard Deviation 10.41 |
| Placebo | Short-term Period: MeanSystolic and Diastolic Blood Pressure | Diastolic blood pressure: Day 1 predose | 78.3 mm Hg | Standard Deviation 12.06 |
Primary
Short-term Period: Mean Temperature
Vital sign measurements are summarized without regard to position (sitting, standing, supine).
Time frame: Day 1 predose and postdose and Day 2
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Mean Temperature | Day 1 predose | 36.7 Degrees Celsius | Standard Deviation 0.51 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Temperature | Day 1 postdose | 36.8 Degrees Celsius | Standard Deviation 0.59 |
| Abatacept (30 mg/kg) | Short-term Period: Mean Temperature | Day 2 | 36.9 Degrees Celsius | Standard Deviation 0.11 |
| Placebo | Short-term Period: Mean Temperature | Day 1 predose | 36.7 Degrees Celsius | Standard Deviation 0.15 |
| Placebo | Short-term Period: Mean Temperature | Day 1 postdose | 36.9 Degrees Celsius | Standard Deviation 0.26 |
| Placebo | Short-term Period: Mean Temperature | Day 2 | 36.9 Degrees Celsius | Standard Deviation 0.12 |
Primary
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).
Time frame: From Day 1 of double-blind period to 1st dose of long-term period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Dizziness (mild) | 1 Events |
| Abatacept (30 mg/kg) | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Oropharyngeal pain (mild) | 1 Events |
| Abatacept (30 mg/kg) | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Diarrhea (mild) | 0 Events |
| Placebo | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Dizziness (mild) | 0 Events |
| Placebo | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Oropharyngeal pain (mild) | 0 Events |
| Placebo | Short-term Period: Number of Adverse Events (AEs) Related to Study Drug | Diarrhea (mild) | 1 Events |
Primary
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.
Time frame: From Day 1 of double-blind period to 1st dose of long-term period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Deaths | 0 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | SAEs | 0 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | AEs | 3 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Discontinued due to AEs | 0 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Acute infusional AEs | 0 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Peri-infusional AEs | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Acute infusional AEs | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Deaths | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Discontinued due to AEs | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | SAEs | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | Peri-infusional AEs | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, Discontinuations and Infusional AEs | AEs | 1 Participants |
Primary
Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities
Laboratory tests consisted of complete blood count, chemistry, and urinalysis.
Time frame: Screening and Days 1 and 2
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | Laboratory Abnormalities | 0 Participants |
| Abatacept (30 mg/kg) | Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | ECG Abnormalities | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | Laboratory Abnormalities | 0 Participants |
| Placebo | Short-term Period: Number of Participants With Clinical Laboratory and Electrocardiogram (ECG) Abnormalities | ECG Abnormalities | 0 Participants |
Secondary
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.
Time frame: Day15 to 56 days post last dose of the long-term period
Population: All participants who received at least 1 dose of abatacept and had an immunogenicity test result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Abatacept-specific Antibodies | 0 Participants |
Secondary
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.
Time frame: Days 15 to 56 days post last dose of the long-term period
Population: All participants who received at least 1 infusion of abatacept during the open-label long-term extension period of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | Deaths | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | SAEs | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | Discontinuations due to AEs | 2 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | AEs | 8 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Death as Outcome, Serious AEs (SAEs), Discontinuations Due to AEs, and Treatment-related AEs | Treatment-related AEs | 6 Participants |
Secondary
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
Time frame: Days 15 to 56 days post last dose of the long-term period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Hemoglobin (low) | 1 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Hemoglobin (high) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Hematocrit (low) | 1 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Hematocrit (high) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Erythrocytes (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Erythrocytes (high) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Platelet count (low or high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Leukocytes (low) | 1 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Leukocytes (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Neutrophils +bands (absolute) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Neutrophils +bands (absolute) (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute lymphocytes (low) | 6 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute lymphocytes (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute monocytes (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute monocytes (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute basophils (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute basophils (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute eosinophils (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests | Absolute eosinophils (high) | 0 Participants |
Secondary
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.
Time frame: Days 15 to 56 days post last dose of the long-term period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, serum (low) | 2 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, serum (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, fasting serum (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, fasting serum (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Protein, total (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Protein, total (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Albumin (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Albumin (high) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Uric acid (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Uric acid (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Protein, urine (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Protein, urine (high) | 1 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, urine (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Glucose, urine (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Blood, urine (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Blood, urine (high) | 5 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | WBC, urine (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | White blood cell (WBC) count, urine (high) | 3 Participants |
Secondary
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:
Time frame: Days 15 to 56 days post last dose of the long-term period
Population: All participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Alkaline phosphatase (ALP) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | ALP (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Aspartate aminotransferase (AST) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | AST (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Alanine aminotransferase (ALT) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | ALT (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | G-glutamyl transferase (GGT) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | GGT (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Bilirubin, total (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Bilirubin, total (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Blood urea nitrogen (BUN) (low) | NA Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | BUN (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Sodium, serum (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Sodium, serum (high) | 1 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Potassium, serum (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Potassium, serum (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Chloride, serum (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Chloride, serum (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Calcium, total (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Calcium, total (high) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Phosphorus, inorganic (low) | 0 Participants |
| Abatacept (30 mg/kg) | Long-term Period: Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests (Continued) | Phosphorus, inorganic (high) | 2 Participants |
Secondary
Maximum (Cmax) Plasma Concentration of Abatacept
Cmax is a drug's maximum, or peak, concentration observed after its administration.
Time frame: Postdosing Day 1
Population: All participants who received at least 1 dose of study drug and had a serum concentration measurement relative to dosing time. n=number of evaluable participants.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Abatacept (30 mg/kg) | Maximum (Cmax) Plasma Concentration of Abatacept | 463.10 ug/mL | Geometric Coefficient of Variation 17 |
Secondary
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.
Time frame: Days 15, 29, 85, 169, 253 and 337
Population: All participants who received at least 1 dose of study drug and had a serum concentration measurement relative to dosing time. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 15 (n=6) | 55.47 ug/mL | Standard Deviation 29.356 |
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 29 (N=9) | 42.69 ug/mL | Standard Deviation 12.534 |
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 85 (n=8) | 18.54 ug/mL | Standard Deviation 11.492 |
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 169 (n=7) | 22.66 ug/mL | Standard Deviation 10.312 |
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 253 (n=7) | 28.24 ug/mL | Standard Deviation 13.883 |
| Abatacept (30 mg/kg) | Minimum (Cmin) Plasma Concentration of Abatacept | Day 337 (n=4) | 25.98 ug/mL | Standard Deviation 6.833 |