Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy Study of a Biologic to Treat Systemic Lupus Erythematosus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02265744
Recruitment Status : Completed
First Posted : October 16, 2014
Results First Posted : January 4, 2019
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE October 15, 2014
First Posted Date  ICMJE October 16, 2014
Results First Submitted Date  ICMJE October 25, 2018
Results First Posted Date  ICMJE January 4, 2019
Last Update Posted Date January 4, 2019
Actual Study Start Date  ICMJE November 13, 2014
Actual Primary Completion Date October 26, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 2, 2019)
Percentage of Participants Who Achieve a BICLA Response (BICLA Response Rate) at Day 169 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 15, 2014)
Proportion of subjects who achieve a BICLA response (BICLA response rate) [ Time Frame: At Day 169 ]
Change History Complete list of historical versions of study NCT02265744 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 2, 2019)
  • Percentage of Participants Who Meet Response Criteria for the SLE Responder Index : SRI(4), SRI(5) and SRI(6) at Day 169 [ Time Frame: 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)
  • Percentage of Participants Who Meet Response Criteria for the SLE Responder Index: SRI(4), SRI(5) and SRI(6) at Day 85 [ Time Frame: 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)
  • Percentage of Participants With BICLA Response (BICLA Response Rate) at Day 85 [ Time Frame: 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.
  • Mean Change From Baseline in CLASI Score at Day 85 and Day 169 [ Time Frame: 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 [ Time Frame: 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.
  • 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 [ Time Frame: 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)
  • Change From Baseline in BILAG-2004 Score of Systemic Lupus Erythematosus (SLE) Activity on Day 85 and Day 169 [ Time Frame: 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.
  • Cumulative Corticosteroid and Immunosuppressant Use [ Time Frame: 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
  • Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Pre-established Events of Special Interest [ Time Frame: 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 Clinically Significant Changes in Vital Signs:Heart Rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At Day 85 and Day 169 ]
    RESPIRATION RATE (RESP) (PER MIN) RESP > 16 OR RESP CHANGE FROM BASELINE > 10
  • Percentage of Participants With Clinically Significant Changes in Vital Signs: Temperature [ Time Frame: At Day 85 and Day 169 ]
    TEMPERATURE (TEMP) (C) TEMP > 38.3 OR TEMP CHANGE FROM BASELINE > 1.6
  • Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: 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
  • Ctrough: Trough Level Serum Concentration of BMS-931699 at Time Point Specified [ Time Frame: 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 [ Time Frame: 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
  • Serum Biomarkers: Anti-Nuclear Antibodies (ANA) [ Time Frame: 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
  • Short Term: Receptor Occupancy Over Time [ Time Frame: At Day 85 and Day 169 ]
    Percent CD4+ Receptor Occupancy and percent CD8+ Receptor Occupancy
  • Percentage of Participants With BMS-931699 Induced Antibody Response Over Time Point Specified [ Time Frame: 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 With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY I [ Time Frame: 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 With Clinically Significant Abnormalities in General Laboratory Tests: HEMATOLOGY II [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ELECTROLYTES 1 [ Time Frame: 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 Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 2 [ Time Frame: 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
  • Number of Participants Clinically Significant Abnormalities in General Laboratory Tests: ELECTROLYTES 3 [ Time Frame: 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 [ Time Frame: 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 : OTHER CHEMISTRY TESTING 2 [ Time Frame: 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 [ Time Frame: 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 : IMMUNOLOGY [ Time Frame: 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;
  • Number of Participants Clinically Significant Abnormalities in General Laboratory Tests : URINALYSIS [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2014)
  • Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], SRI(5) and SRI(6) [ Time Frame: At Day 169 ]
  • Proportion of subjects who meet response criteria for the SLE Responder Index(4) [SRI(4)], SRI(5) and SRI(6) [ Time Frame: At Day 85 ]
  • Proportion of subjects with BICLA response [ Time Frame: At Day 85 ]
  • Change from baseline in CLASI score [ Time Frame: At Day 85 and Day 169 ]
  • Percentage of subjects with an improvement of >4 or a decrease of >50% from baseline in their Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score [ Time Frame: At Day 85 and Day 169 ]
  • Change from baseline in arthritis, as assessed by American College of Rheumatology (ACR) 28-joint count of tender and swollen joints [ Time Frame: At Day 85 and Day 169 ]
  • Change from baseline in other indices systemic lupus erythematosus (SLE) activity over time [ Time Frame: At Day 85 and Day 169 ]
    (Overall British Isles Lupus Assessment Group-2004 score, Overall Systemic Lupus Erythematosus Disease Activity Index-2K score and Overall Physician's Global Assessment of Disease Activity (MDGA) score)
  • Cumulative corticosteroid and immunosuppressant use over time [ Time Frame: At Day 85 and Day 169 ]
  • Incidence and severity of all Adverse Events (AEs), Serious AEs, and pre-established Events of Special Interest [ Time Frame: At Day 85 and Day 169 ]
  • Incidence and severity of clinically significant changes in vital signs [ Time Frame: At Day 85 and Day 169 ]
  • Incidence and severity of clinically significant electrocardiogram (ECG) abnormalities [ Time Frame: At Day 85 and Day 169 ]
  • Incidence and severity of clinically significant abnormalities in general laboratory tests [ Time Frame: At Day 85 and Day 169 ]
  • Ctrough: Trough level serum concentration of BMS-931699 at time points specified [ Time Frame: At Day 85 and Day 169 ]
  • Serum biomarkers C3, C4, anti-dsDNA, ANA and other auto-antibodies and other applicable visits [ Time Frame: At Day 85 and Day 169 ]
  • Receptor occupancy over time [ Time Frame: At Day 85 and Day 169 ]
  • Proportion of subjects with BMS-931699 induced antibody response over time points specified [ Time Frame: At Day 85 and Day 169 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of a Biologic to Treat Systemic Lupus Erythematosus
Official Title  ICMJE A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Lulizumab Pegol vs. Placebo on a Background of Limited Standard of Care in the Treatment of Subjects With Active Systemic Lupus Erythematosus
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Lupus
Intervention  ICMJE
  • Drug: BMS-931699
    Other Name: lulizumab pegol
  • Drug: Placebo matching BMS-931699
Study Arms  ICMJE
  • Experimental: Experimental:Arm A: BMS-931699
    12.5mg subcutaneous (SC) injection Weekly dosing
    Intervention: Drug: BMS-931699
  • Experimental: Experimental:Arm B: BMS-931699
    12.5mg SC injection Every other Week dosing
    Intervention: Drug: BMS-931699
  • Experimental: Experimental:Arm C: BMS-931699
    5mg SC injection Every other Week dosing
    Intervention: Drug: BMS-931699
  • Experimental: Experimental:Arm D: BMS-931699
    1.25mg SC injection Every other Week dosing
    Intervention: Drug: BMS-931699
  • Placebo Comparator: Placebo Comparator: Arm E: Placebo matching BMS-931699
    0mg SC injection Weekly dosing
    Intervention: Drug: Placebo matching BMS-931699
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 2, 2019)
730
Original Estimated Enrollment  ICMJE
 (submitted: October 15, 2014)
350
Actual Study Completion Date  ICMJE November 30, 2017
Actual Primary Completion Date October 26, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Diagnosed with active lupus nephritis, multiple sclerosis or rheumatoid arthritis
  • Diagnosed with active tuberculosis or an ongoing infection with a bacteria or a virus
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   Chile,   Colombia,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Lebanon,   Mexico,   Netherlands,   Peru,   Poland,   Puerto Rico,   Romania,   Russian Federation,   South Africa,   Spain,   Taiwan,   United States
Removed Location Countries Qatar
 
Administrative Information
NCT Number  ICMJE NCT02265744
Other Study ID Numbers  ICMJE IM128-027
2014-002184-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP