Safety and Efficacy Study of a Biologic to Treat Systemic Lupus Erythematosus
- Registration Number
- NCT02265744
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Study evaluating the safety and efficacy of a novel biologic in the treatment of systemic lupus erythematosus in male and female adults. Patients who qualify will be randomized to either active BMS-931699 or placebo for initially, up to 24 weeks. Patients who complete the initial 24 weeks of treatment and who are responding to therapy will have the option to continue receiving BMS-931699 as part of a long-term extension (LTE). Disease activity and safety will be assessed over the course of the study through laboratory values, various rating scales accepted in systemic lupus erythematosus studies and patient self reporting.
- Detailed Description
1. Subjects completing Day 169 (24 weeks) on study medication may be eligible to enter an optional LTE period
2. The LTE period will remain blinded but will no longer have a placebo arm:
* Subjects will remain on their originally assigned treatment arm unless they were on placebo
* Subjects initially randomized to placebo arm will be automatically re-randomized into one of the existing active arms at Day 169 (24 weeks)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 730
- Male or female aged between 18 to 70 (included)
- Diagnosed with active systemic lupus erythematosus by a doctor
- Disease must be in patient's joints or on the skin at a minimum
- Taking other medications is allowed but some are excluded
- Diagnosed with active lupus nephritis, multiple sclerosis or rheumatoid arthritis
- Diagnosed with active tuberculosis or an ongoing infection with a bacteria or a virus
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental:Arm D: BMS-931699 BMS-931699 1.25mg SC injection Every other Week dosing Experimental:Arm A: BMS-931699 BMS-931699 12.5mg subcutaneous (SC) injection Weekly dosing Placebo Comparator: Arm E: Placebo matching BMS-931699 Placebo matching BMS-931699 0mg SC injection Weekly dosing Experimental:Arm C: BMS-931699 BMS-931699 5mg SC injection Every other Week dosing Experimental:Arm B: BMS-931699 BMS-931699 12.5mg SC injection Every other Week dosing
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieve a BICLA Response (BICLA Response Rate) at Day 169 At Day 169 The British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) is a measure of systemic lupus erythematosus (SLE) response. BICLA is defined as: British Isle Lupus Assessment Group improvement, defined as BILAG As at Baseline improved to B/C/D, and BILAG Bs at baseline improved to C/D, and no BILAG worsening in other BILAG organ systems such that there are no new BILAG As or greater than 1 new BILAG B; and no worsening in the SLEDAI-2K total score compared to Baseline (defined as no increase in SLEDAI total score); and no worsening in the physician's global assessment (MDGA) of disease activity ("no worsening" is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale \[VAS\]) compared to Baseline.
- Secondary Outcome Measures
Name Time Method Change From Baseline in BILAG-2004 Score of Systemic Lupus Erythematosus (SLE) Activity on Day 85 and Day 169 At baseline, Day 85 and Day 169 Overall British Isles Lupus Assessment Group-2004 score, BILAG Scores: A=Severe disease activity, B=Moderate disease activity, C=Mild disease, D=Inactive disease but previously affected, E=System never involved.The categories are converted to a numeric score (A=9, B=3, C=1, D=0, E=0) and treated as a continuous variable. Higher score= more severe disease activity.
Ctrough: Trough Level Serum Concentration of BMS-931699 at Time Point Specified Day 169 Pharmacokinetics of BMS-931699 derived from serum concentration versus time data; Ctrough = Trough level serum concentration of BMS-931699 at time point specified Pharmacokinetic Population: defined as all subjects who receive any study medication and have any available concentration-time data.
Serum Biomarkers C3, C4 At Day 85 and Day 169 Serum biomarkers C3, C4, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nuclear antibody (ANA) and other autoantibodies were measured from blood serum samples collected on Day 85 and Day 169
Percentage of Participants Who Meet Response Criteria for the SLE Responder Index : SRI(4), SRI(5) and SRI(6) at Day 169 At Day 169 SRI is the Systemic Lupus Erythematosus Responder Index. An SRI(4) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 4 points AND (a)no worsening in the physician's global assessment (MDGA) of disease activity ("no worsening" is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale \[VAS\]) compared to Baseline) AND (b) no new BILAG-2004 Index A organ system score AND (c)no more than one new or worsening BILAG-2004 Index B organ system scores.
An SRI(5) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 5 points AND (a) AND (b) AND (c).
An SRI(6) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 6 points AND (a) AND (b) AND (c) The outcomes are better in increasing order from SRI(4) to SRI(5) to SRI(6)Mean Change From Baseline in CLASI Score at Day 85 and Day 169 At Day 85 and Day 169 Mean change from baseline, CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index. Scores can range from 0 to 70 with higher scores denoting greater disease activity or damage.
Percentage of Participants With an Improvement of >4 or a Decrease of >50% From Baseline in Their Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Score At Day 85 and Day 169 Mean change from baseline, CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index. Scores can range from 0 to 70 with higher scores denoting greater disease activity or damage.
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Pre-established Events of Special Interest On or after the first dose date of short-term study medication and up to 42 days post last short-term dose date or up to the day prior to the first dose of long-term extension period, whichever is earlier Although there are no identified risks for BMS-931699, BMS has developed a list of events of special interest for the BMS-931699 program based on the known biologic class effects, the mechanism of action of BMS-931699, overall potential consequences of mmunosuppression, and preliminary data from unblinded clinical trials. Event categories of special interest for this study may include, but are not limited to: Infections, Autoimmunity, Malignancies, Injection-related reactions
Percentage of Participants With BICLA Response (BICLA Response Rate) at Day 85 At Day 85 BICLA is defined as: British Isle Lupus Assessment Group improvement, defined as BILAG As at Baseline improved to B/C/D, and BILAG Bs at baseline improved to C/D, and no BILAG worsening in other BILAG organ systems such that there are no new BILAG As or greater than 1 new BILAG B; and no worsening in the SLEDAI-2K total score compared to Baseline (defined as no increase in SLEDAI total score); and no worsening in the physician's global assessment (MDGA) of disease activity ("no worsening" is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale \[VAS\]) compared to Baseline; No changes in concomitant medications according to the following criteria: No increase of or addition of a new immunosuppressant agent (azathioprine,mycophenolic acid/mycophenolate mofetil, methotrexate, anti-malarial, leflunomide) over baseline levels; No increase in corticosteroid dose above baseline level outside of those allowed per protocol.
Cumulative Corticosteroid and Immunosuppressant Use Up to one day prior to the first dose of long-term extension period or up to 42 days post last short-term dose date, which ever is earlier Percent of participants requiring use of corticosteroids and mmunosuppressants use over time
Short Term: Receptor Occupancy Over Time At Day 85 and Day 169 Percent CD4+ Receptor Occupancy and percent CD8+ Receptor Occupancy
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities Up to 42 days post last dose of short-term double-blind study medication or up to the day prior to the start of long-term extension period, whichever is earlier. QTc (corrected QT) Fridericia, PR Interval, QRS Interval and Change from baseline in QTCF
Percentage of Participants Who Meet Response Criteria for the SLE Responder Index: SRI(4), SRI(5) and SRI(6) at Day 85 At Day 85 SRI is the Systemic Lupus Erythematosus Responder Index. An SRI(4) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 4 points AND (a)no worsening in the physician's global assessment (MDGA) of disease activity ("no worsening" is defined as less than 10% worsening, equivalent to a 10mm increase on a 100mm visual analog scale \[VAS\]) compared to Baseline) AND (b) no new BILAG-2004 Index A organ system score AND (c)no more than one new or worsening BILAG-2004 Index B organ system scores.
An SRI(5) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 5 points AND (a) AND (b) AND (c).
An SRI(6) Response is defined as a reduction in Day 1 SLEDAI-2K disease activity score of ≥ 6 points AND (a) AND (b) AND (c) The outcomes are better in increasing order from SRI(4) to SRI(5) to SRI(6)Change From Baseline in Arthritis, as Assessed by American College of Rheumatology (ACR) 28-joint Count of Tender and Swollen Joints on Day 85 and Day 169 At baseline, Day 85 and Day 169 Mean Change from Baseline Over Time; Measured by Disease Activity Score 28: A single score on a continuous scale (0-9.4). The level of RA disease activity can be interpreted as low (DAS28 \<=3.2),moderate (3.2 \< DAS28 \<=5.1), or as high disease activity (DAS28 \> 5.1)
Percentage of Participants With Clinically Significant Changes in Vital Signs:Heart Rate At Day 85 and Day 169 HEART RATE (HR) Beats per min (BPM): HR \> 100 AND CHANGE FROM BASELINE \> 30 OR HR \< 55 AND CHANGE FROM BASELINE \< -15
Percentage of Participants With Clinically Significant Changes in Vital Signs: Systolic and Diastolic Blood Pressure At Day 85 and Day 169 SYSTOLIC BLOOD PRESSURE (SYSBP) (MMHG); SYSBP \> 140 AND CHANGE FROM BASELINE \> 20 OR SYSBP \< 90 AND CHANGE FROM BASELINE \< -20; DIASTOLIC BLOOD PRESSURE (DIABP) \> 90 AND CHANGE FROM BASELINE \> 10 OR DIABP \< 55 AND CHANGE FROM BASELINE \< -10;
Percentage of Participants With Clinically Significant Changes in Vital Signs: Respiration Rate At Day 85 and Day 169 RESPIRATION RATE (RESP) (PER MIN) RESP \> 16 OR RESP CHANGE FROM BASELINE \> 10
Serum Biomarkers: Anti-Nuclear Antibodies (ANA) At Day 85 and Day 169 Serum biomarkers C3, C4, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nuclear antibody (ANA) and other autoantibodies were measured from blood serum samples collected on Day 85 and Day 169. No anti-dsDNA data was available for this report
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 2 Up to 42 days post last dose of study medication in short-term or long-term extension period BICARBONATE MMOL/L H \> 1.2×ULN IF PRE-RX IS MISSING OR \> 1.2×ULN IF PRE-RX \<= ULN OR \> 1.2×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN; BICARBONATE MMOL/L L \< 0.8×LLN IF PRE-RX IS MISSING OR \< 0.8×LLN IF PRE-RX \>= LLN OR \< 0.8×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN; POTASSIUM, SERUM MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.1×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN; POTASSIUM, SERUM MMOL/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN; MAGNESIUM, SERUM MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.1×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN MAGNESIUM, SERUM MMOL/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN
Percentage of Participants With Clinically Significant Changes in Vital Signs: Temperature At Day 85 and Day 169 TEMPERATURE (TEMP) (C) TEMP \> 38.3 OR TEMP CHANGE FROM BASELINE \> 1.6
Percentage of Participants With BMS-931699 Induced Antibody Response Over Time Point Specified Day 169 Immunogenicity defined as positive for anti-drug antibodies post-baseline measurement if baseline missing or negative. If baseline is positive, then immunogenicity is defined as a positive post-baseline measurement with titer value 4 times greater than baseline. (A) all subjects with a laboratory reported positive antibody responses to BMS-931699 during the short-term double-blind treatment period are included. Overall: At least one positive sample relative to baseline during short-term double-blind and follow-up period.
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests ELECTROLYTES 1 Up to 42 days post last dose of study medication in short-term or long-term extension period CALCIUM, TOTAL MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.1×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN; CALCIUM, TOTAL MMOL/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN; CHLORIDE, SERUM MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.1×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN; CHLORIDE, SERUM MMOL/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN;
Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY I Up to 42 days post last dose of study medication in short-term or long-term extension period HEMATOLOGY I: ERYTHROCYTE/PLATELET ATTRIBUTES HEMOGLOBIN G/L L \< 0.85×PRE-RX; HEMATOCRIT VOL L \< 0.85×PRE-RX; PLATELET COUNT X10\*9 C/L H \> 1.5×ULN (ULN = Upper Limit of Normal) IF PRE-RX IS MISSING OR \> 1.5×ULN PLATELET COUNT X10\*9 C/L L \< 0.85×LLN (LLN = Lower Limit of Normal) IF PRE-RX IS MISSING OR \< 0.85×LLN IF PRE-RX \>= LLN OR \< 0.85×PRE-RX IF PRE-RX \< LLN; ERYTHROCYTES RBC X10\*12 C/L L \< 0.85×PRE-RX HEMATOLOGY II QUANTITATIVE WBC : LEUKOCYTES X10\*9 C/L H \> 1.2×ULN IF PRE-RX IS MISSING OR \> 1.2×ULN IF LLN \<= PRE-RX \<= ULN OR \> 1.5×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN; LEUKOCYTES WBC X10\*9 C/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF LLN \<= PRE-RX \<= ULN OR \< 0.85×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : URINALYSIS Up to 42 days post last dose of study medication in short-term or long-term extension period QUALITATIVE URINE CHEMISTRY: BLOOD, URINE N/A H \>= 2 IF PRE-RX IS MISSING OR \>= 2 IF PRE-RX \< 1 OR \>= 2×PRE-RX IF PRE-RX \>= 1 GLUCOSE, URINE N/A H \>= 1 IF PRE-RX IS MISSING OR \>= 1 IF PRE-RX \< 1 OR \>= 2×PRE-RX IF PRE-RX \>= 1 PROTEIN, URINE UNKNOWN H \>= 2 IF PRE-RX IS MISSING OR \>= 2 IF PRE-RX \< 1 OR \>= 2×PRE-RX IF PRE-RX \>= 1 URINALYSIS II URINE WBC + RBC ; RBC, URINE HPF H \>= 2 IF PRE-RX IS MISSING OR \>= 2 IF PRE-RX \< 2 OR \>= 4 IF PRE-RX \>= 2 WBC, URINE HPF H \>= 2 IF PRE-RX IS MISSING OR \>= 2 IF PRE-RX \< 2 OR \>= 4 IF PRE-RX \>= 2
Change From Baseline in the SLEDAI-2K Score of SLE Activity on Day 85 and Day 169 At baseline, Day 85 and Day 169 Systemic Lupus Erythematosus Disease Activity Index, SLEDAI; Version 2000, also known as SLEDAI-2K. The SLEDAI-2K score is a weighted, cumulative index of lupus disease activity. SLEDAI-2K is calculated from 24 individual descriptors across 9 organ systems; 0 indicates inactive disease and the maximum theoretical score is 105.
Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) on Day 85 and Day 169 At baseline, Day 85 and Day 169 Physician Global Assessment of Arthritis was measured by asking the physician to assess the participant's current arthritis disease activity by placing a vertical line on a 0 to 100 millimeter (mm) visual analog scale (VAS), where 0 mm = very good and 100 mm = very bad.
Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY II Up to 42 days post last dose of study medication in short-term or long-term extension period WBC DIFFERENTIAL COUNT: BASOPHILS (ABSOLUTE) X10\*9 C/L H \> 0.4; BLASTS (ABSOLUTE) X10\*9 C/L H \> 0; EOSINOPHILS (ABSOLUTE) EOSA X10\*9 C/L H \> 0.75; LYMPHOCYTES (ABSOLUTE) X10\*9 C/L H \> 7.5; LYMPHOCYTES (ABSOLUTE) X10\*9 C/L L \< 0.75; MONOCYTES (ABSOLUTE) X10\*9 C/L H \> 2; NEUTROPHILS (ABSOLUTE) X10\*9 C/L L \< 1.5 IF PRE-RX IS MISSING OR \< 1.5 IF PRE-RX \>= 1.5 OR \< 0.85×PRE-RX IF PRE-RX \< 1.5; COAGULATION activated Partial thromboplastin time (APTT) SEC H \> 1.5×ULN; INTL NORMALIZED RATIO (INR) INR FRACTION H \> 1.5×ULN PROTHROMBIN TIME (PT) PT SEC H \> 1.5×ULN
Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests : LIVER FUNCTION TESTS Up to 42 days post last dose of study medication in short-term or long-term extension period LIVER FUNCTION TESTS:ALKALINE PHOSPHATASE (ALP) ALP U/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN; ALANINE AMINOTRANSFERASE (ALT) ALT U/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN; ASPARTATE AMINOTRANSFERASE (AST) AST U/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN; BILIRUBIN, DIRECT UMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN G-GLUTAMYL TRANSFERASE (GGT) GGT U/L H \> 1.15×ULN IF PRE-RX IS MISSING OR \> 1.15×ULN IF PRE-RX \<= ULN OR \> 1.2×PRE-RX IF PRE-RX \> ULN BILIRUBIN, TOTAL UMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN
Number of Participants With Clinically Significant Abnormalities in General Laboratory Tests: KIDNEY FUNCTION TESTS Up to 42 days post last dose of study medication in short-term or long-term extension period KIDNEY FUNCTION TESTS:BLOOD UREA NITROGEN MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.2×PRE-RX IF PRE-RX \> ULN CREATININE UMOL/L H \> 1.5×ULN IF PRE-RX IS MISSING OR \> 1.5×ULN IF PRE-RX \<= ULN OR \> 1.33×PRE-RX IF PRE-RX \> ULN GLOMERULAR FILTRATION RATE, CALC. ML/S/M\*2 L \< 0.8×PRE-RX; UREA UREA MMOL/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.2×PRE-RX IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 2 Up to 42 days post last dose of study medication in short-term or long-term extension period OTHER CHEMISTRY TESTING LIPID TESTS: CHOLESTEROL, TOTAL (TC) MMOL/L H \> 1.2×ULN IF PRE-RX IS MISSING OR \> 1.2×ULN IF PRE-RX \<= ULN OR \> 1.2×PRE-RX IF PRE-RX \> ULN TRIGLYCERIDES, FASTING MMOL/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.5×PRE-RX IF PRE-RX \> ULN PANCREATIC TESTS: AMYLASE, TOTAL U/L H \> 1.5×ULN; LIPASE, TOTAL (TURBIDIMETRIC ASSAY) U/L H \> 1.5×ULN; LIPASE, TOTAL (COLORIMETRIC ASSAY) U/L H \> 1.5×ULN; ENDOCRINE TESTS:CORTISOL, AM NMOL/L L \< 138 THYROID STIMULATING HORMONE (TSH) TSH MU/L H \> 1.5×ULN IF PRE-RX IS MISSING OR \> 1.5×ULN IF PRE-RX \<= ULN OR \> 2×PRE-RX IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 3 Up to 42 days post last dose of study medication in short-term or long-term extension period OTHER CHEMISTRY TESTING CARDIAC TESTS: CREATINE KINASE (CK) CK U/L H \> 1.5×ULN IF PRE-RX IS MISSING OR \> 1.5×ULN IF PRE-RX \<= ULN OR \> 1.5×PRE-RX IF PRE-RX \> ULN; TROPONIN-I, CARDIAC SPECIFIC UG/L H \> ULN; METABOLITE TESTS:URIC ACID URIC MMOL/L H \> 1.2×ULN IF PRE-RX IS MISSING OR \> 1.2×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN; CHEM TEST, MULTI INDICATIONS : LACTATE DEHYDROGENASE (LD) LD U/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.5×PRE-RX IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 3 Up to 42 days post last dose of study medication in short-term or long-term extension period SODIUM, SERUM MMOL/L H \> 1.05×ULN IF PRE-RX IS MISSING OR \> 1.05×ULN IF PRE-RX \<= ULN OR \> 1.05×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN SODIUM, SERUM MMOL/L L \< 0.95×LLN IF PRE-RX IS MISSING OR \< 0.95×LLN IF PRE-RX \>= LLN OR \< 0.95×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN PHOSPHORUS, INORGANIC PHOS MMOL/L H \> 1.25×ULN IF PRE-RX IS MISSING OR \> 1.25×ULN IF PRE-RX \<= ULN OR \> 1.25×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN PHOSPHORUS, INORGANIC PHOS MMOL/L L \< 0.85×LLN IF PRE-RX IS MISSING OR \< 0.85×LLN IF PRE-RX \>=LLN OR \< 0.85×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : OTHER CHEMISTRY TESTING 1 Up to 42 days post last dose of study medication in short-term or long-term extension period GLUCOSE TESTS:GLUCOSE, FASTING SERUM MMOL/L H \> 1.3×ULN IF PRE-RX IS MISSING OR \> 1.3×ULN IF PRE-RX \<= ULN OR \> 2×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN GLUCOSE, FASTING SERUM MMOL/L L \< 0.8×LLN IF PRE-RX IS MISSING OR \< 0.8×LLN IF PRE-RX \>= LLN OR \< 0.8×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN; PROTEIN TESTS:ALBUMIN G/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN PROTEIN, TOTAL G/L H \> 1.1×ULN IF PRE-RX IS MISSING OR \> 1.1×ULN IF PRE-RX \<= ULN OR \> 1.1×PRE-RX IF PRE-RX \> ULN OR \> ULN IF PRE-RX \< LLN PROTEIN, TOTAL G/L L \< 0.9×LLN IF PRE-RX IS MISSING OR \< 0.9×LLN IF PRE-RX \>= LLN OR \< 0.9×PRE-RX IF PRE-RX \< LLN OR \< LLN IF PRE-RX \> ULN
Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : IMMUNOLOGY Up to 42 days post last dose of study medication in short-term or long-term extension period IMMUNE ACTIVATION MARKERS:C-REACTIVE PROTEIN (CRP) CRP MG/L H \> 1.5×ULN; CRP, HIGH SENSITIVITY MG/L H \> 1.5×ULN;
Trial Locations
- Locations (78)
The Arthritis Center
🇺🇸Palm Harbor, Florida, United States
Coeur D'Alene Arthrit Clin
🇺🇸Coeur d'Alene, Idaho, United States
Heartland Research Associates, Llc
🇺🇸Wichita, Kansas, United States
Albuquerque Clinical Trials
🇺🇸Albuquerque, New Mexico, United States
Joint and Muscle Medical Care and Research Institute (JMMCRI)
🇺🇸Charlotte, North Carolina, United States
Pmg Research Of Salisbury
🇺🇸Salisbury, North Carolina, United States
East Penn Rheumatology Associates, P.C.
🇺🇸Bethlehem, Pennsylvania, United States
Tekton Research Inc
🇺🇸Austin, Texas, United States
Arthritis Northwest
🇺🇸Spokane, Washington, United States
Instituto de Asistencia Reumatologica Integral
🇦🇷San Fernando, Buenos Aires, Argentina
Clinica De Reumatologia
🇦🇷Rosario, Santa FE, Argentina
CPCLIN Centro de Pesquisas Clinicas LTDA
🇧🇷Sao Paulo, Brazil
Lar Escola AACD
🇧🇷Sao Paulo, Brazil
McMaster University
🇨🇦Hamilton, Ontario, Canada
CHU de Quebec Research Centre
🇨🇦Quebec, Canada
Centro De Estudios Reumatologicos
🇨🇱Santiago De Chile, Metropolitana, Chile
Servimed E.U
🇨🇴Bucaramanga, Santander, Colombia
Campus Charite Mitte
🇩🇪Berlin, Germany
Medizinsche Universitaetsklinik Freiburg
🇩🇪Freiburg, Germany
Universitaetshautklinik Heidelberg
🇩🇪Heidelberg, Germany
Johannes Gutenberg - Universitaet
🇩🇪Mainz, Germany
St Jude Hospital Yorba Linda
🇺🇸Fullerton, California, United States
Harbor UCLA Medical Center
🇺🇸Torrance, California, United States
University Of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Center For Rheumatology, Immunology And Arthritis
🇺🇸Fort Lauderdale, Florida, United States
Jefrey D. Lieberman, Md., Pc
🇺🇸Decatur, Georgia, United States
Beth Israel Deaconess Med. Center Div. Of Gastroenterology
🇺🇸Boston, Massachusetts, United States
Physician Research Collaboration, Llc
🇺🇸Lincoln, Nebraska, United States
North Shore Lij Health System
🇺🇸Great Neck, New York, United States
The Feinstein Institute For Medical Research
🇺🇸Manhasset, New York, United States
Allegheny-Singer Research Institute (Asri)
🇺🇸Pittsburgh, Pennsylvania, United States
Toronto Western Hospital, University Health Network
🇨🇦Toronto, Ontario, Canada
Consultorio Medico de Reumatologia Dr.Jesus Alberto Lopez Garcia
🇲🇽León, Guanajuato, Mexico
Centro Mineiro De Pesquisa
🇧🇷Juiz de Fora, Minas Gerais, Brazil
Servicos Especializados em Reumatologia SER
🇧🇷Savaldor, Bahia, Brazil
LMK Servicos Medicos S S Ltda
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
🇲🇽San Luis Potosi, Mexico
Instituto De Ginecologia Y Reproduccion Inv. Clinical Sac
🇵🇪Lima, Peru
Hospital San Borja Arriaran
🇨🇱Santiago, Region Metropolitana, Chile
Local Institution
🇨🇳Taoyuan, Taiwan
Centre De Recherche Musculo-Squelettique
🇨🇦Trois-rivieres, Quebec, Canada
Hospital General De Agudos J.M. Ramos Mejia
🇦🇷Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina
Clinica De La Costa
🇨🇴Barranquilla, Colombia
Infektologiai-Hepatologiai Osztaly
🇭🇺Gyula, Hungary
CINTRE - Centro de investigacion y tratamiento reumatologico, S.C.
🇲🇽Mexico City, Distrito Fededral, Mexico
Hospital Nacional Cayetano Heredia
🇵🇪Lima, Peru
Medyczne Centrum Hetmanska Indywidualna Spec. Praktyka Lekar
🇵🇱Poznan, Poland
Instituto Nacional De Ciencias Medicas Y Nutricion S.Z.
🇲🇽Distrito Federal, Mexico
Karma Clinical Trials Inc.
🇨🇦St. John's, Newfoundland and Labrador, Canada
Clinica de Investigacion en Reumatologia y Obesidad S.C.
🇲🇽Guadalajara, Jalisco, Mexico
Centro de Radiodiagnostico Computarizado Medico de Tabasco S.A. de C.V.
🇲🇽Villahermosa, Tabasco, Mexico
Riesgo De Fractura
🇨🇴Bogota, Cundinamarca, Colombia
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Colombia
Clinica Anglo Americana
🇵🇪Lima, Peru
Spitalul Clinic de Recuperare Iasi
🇷🇴Iasi, Romania
Borgyogyaszati Klinika
🇭🇺Szeged, Hungary
Instituto para el DeSarrollo Integral de la Salud S de RL de CV
🇲🇽Mexico, Distrito Federal, Mexico
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
Centro Medico Varginha
🇧🇷Varginha, Minas Gerais, Brazil
Rheumatology Associates Of North Alabama, P.C.
🇺🇸Huntsville, Alabama, United States
Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
🇺🇸Long Beach, California, United States
Instituto De Investigaciones Clinicas De Mar Del Plata
🇦🇷Mar Del Plata, Buenos Aires, Argentina
Centro Consultora Integral de Salud SRL
🇦🇷Cordoba, Argentina
Cip Pesquisas Medicas
🇧🇷Goiania, Goias, Brazil
Edumed - Educacao em Saude S/S LTDA
🇧🇷Curitiba, Parana, Brazil
Budai Irgalmasrendi Korhaz
🇭🇺Budapest, Hungary
Azienda Ospedaliera Luigi Sacco
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Italy
Policlinico Umberto I
🇮🇹Roma, Italy
Arcispedale S. Anna
🇮🇹Cona - Ferrara, Italy
Azienda Ospedaliera Di Padova
🇮🇹Padova, Italy
Centro Integral En Reumatologia Sa De Cv
🇲🇽Guadalajara, Jalisco, Jalisco, Mexico
Unidad Reumatologica Las Americas, S.C. P.
🇲🇽Yucatan, Mexico
Sf. Maria Clinical Hospital,Bucharest
🇷🇴Bucharest, Romania
Hospital Carlos Haya De Malaga
🇪🇸Malaga, Spain
Hospital Meixoeiro
🇪🇸Vigo, Spain
Hosp Univer 12 De Octubre
🇪🇸Madrid, Spain
The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States