A Phase IIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept vs Placebo on a Background of Oral Glucocorticosteroids in the Treatment of Subjects With Systemic Lupus Erythematosus and the Prevention of Subsequent Lupus Flares
Overview
- Phase
- Phase 2
- Intervention
- Abatacept
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 183
- Locations
- 13
- Primary Endpoint
- OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
The purpose of this clinical research study is to learn whether Abatacept can treat and prevent lupus flares; specifically, in patients with active lupus flares in at least one of three organ systems: skin (discoid lesions); inflammation of the lining of the heart (pericarditis), or inflammation of the lining of the lung (pleuritis/pleurisy); or inflammation of more than 4 joints (arthritis). All participants will receive prednisone or prednisone-equivalent treatment in combination with study medication. The safety of this treatment will also be studied.
Investigators
Eligibility Criteria
Inclusion Criteria
- •participants must be diagnosed with SLE and be experiencing an active lupus flare in at least one of three organ systems: skin (discoid lesions), inflammation of the lining of the heart (pericarditis), or inflammation of the lining of the lung (pleuritis/pleurisy); or inflammation of more than 4 joints within 14 days of a screening visit (arthritis)
- •Stable dose of prednisone (\<30mg) for at least one month
Exclusion Criteria
- •participants experiencing an active lupus flare in the kidney or central nervous systems
- •Treatment with a stable dose of azathioprine, mycophenolate mofetil, hydroxychloroquine, chloroquine, or methotrexate for less than three months prior to the study
- •participants with active viral or bacterial infections
- •participants with any other autoimmune disease as a main diagnosis
- •Prior treatment with rituximab
Arms & Interventions
Abatacept + Prednisone
Double Blind Period
Intervention: Abatacept
Abatacept + Prednisone
Double Blind Period
Intervention: Prednisone
Placebo + Prednisone
Double Blind Period
Intervention: Placebo
Placebo + Prednisone
Double Blind Period
Intervention: Prednisone
Abatacept
Open Label
Intervention: Abatacept
Outcomes
Primary Outcomes
OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Sodium (serum): \<0.95x LLN or \>1.05x ULN (if pre-Rx\<LLN, then \<0.95x pre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.05x pre-Rx or \<LLN); Potassium (serum), Chloride (serum), protein (total): \<0.9x LLN or \>1.1xULN (if pre-Rx \<LLN, then \<0.9xpre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1xpre-Rx or \<LLN; Calcium (total): \<0.8xLLN or \>1.2xULN (if pre-Rx \<LLN, then \<0.75x pre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.25x pre-Rx or \<LLN.
OL; Number of Participants With MAs in Urinalysis
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs in urinalysis, Protein, glucose, blood, Leukocyte esterase, red blood cells (RBC), white blood cells (WBC): \>=2+ (or, if value \>=4, or if pre-Rx value = 0 or 0.5, then \>= 2\* or if pre-Rx value =1, then \>=3, or if pre-Rx = 2 or 3, then \>=4); protein (24 hour urine): \>1000 mg/24 hrs and \>=2\* pre-Rx; Glomerular filtration rate (GFR): \<=60 mL/min/1.73m\^2 or \> 15% change from baseline; Protein/creatinine ratio: \> 100 mg/mmol.
Open Label Period (OL); Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs, Drug Related AEs or SAEs and Discontinued Due to AEs
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs or SAEs: events with a relationship to the study therapy of certain; probable; possible; or missing.
OL; Number of Participants With Significant AEs of Special Interest
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs of particular importance were associated with the use of immunomodulatory agents. Number of participants with infections, malignant Neoplasms, pre-specified autoimmune disorders, acute-infusional AEs and peri-infusional AEs were recorded.
OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MMAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Leukocytes: \<0.75\* LLN or \>1.25\* ULN (or, if pre-Rx value \<LLN, then \<0.8\* pre-Rx or \>ULN. If pre-Rx value \>ULN, then \>1.2\* pre-Rx or \<LLN; Neutrophils+bands (absolute): \<1.00\* 10\^3 cells/microliter (c/uL); Lymphocytes (absolute): \<0.75\* 10\^3 c/uL or \>7.50\* 10\^3 c/uL; Monocytes (absolute): \>2000/mm\^3; Basophils (absolute): \>0.40\* 10\^3 c/uL; Eosinophils (absolute): \>0.75\* 10\^3 c/uL.
OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MAs are laboratory measurements marked as abnormal, as per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Glucose: \<65 mg/dL or \>220 mg/dL; Glucose (fasting serum): \<0.8\* LLN or \>1.5 ULN (if pre-Rx \<LLN, then \<0.8\* pre-Rx or \>ULN. If pre-Rx \>ULN, then \>2.0\* pre-Rx or \<LLN; Albumin: \<0.9\* LLN (if pre-Rx \<LLN, then \<0.75 \* pre-Rx); cholesterol (total): \>2\* pre-Rx; triglycerides: \>=2.5\* ULN, or if pre Rx\>ULN then use \>2.5\* pre Rx; fasting triglycerides: \>=2.0\* ULN, or if pre Rx\>ULN then use \>2.0\* pre Rx.
Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare
Time Frame: From start of corticosteroid taper to Day 365
SLE flares scored using BILAG:A:presence of =\>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved. Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin: \>3 g/dL decrease from pre-treatment (pre-Rx) value; hematocrit: \<0.75\* pre-Rx value; erythrocyte count: \<0.75\* pre-Rx value; platelet count: \<0.67\* lower limit of normal (LLN) or \>1.5\* upper limit of normal (ULN) (or, if pre-Rx value \<LLN, then \<0.5\* pre-Rx value or \<100000/mm\^3).
OL; Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), Gamma-glutamyl Transferase (GGT), Bilirubin(Total), Blood Urea Nitrogen (BUN), Creatinine
Time Frame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, GGT: \>2\* ULN (if pre-Rx \>ULN, then \>3\* pre-Rx); AST, ALT: \>3\* ULN (if pre-Rx \>ULN, then \>4\* pre-Rx). Bilirubin (total): \>2\* ULN (if pre-Rx \>ULN, then \>4\* pre-Rx), BUN:\>2\* pre-Rx; Creatinine:\>1.5\* pre-Rx.
Secondary Outcomes
- DB; Number of Participants With MAs in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With Clinically Significant Abnormal Vital Signs and/or Physical Examination Findings(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment(After the first dose of open-label period)
- DB; Number of Participants Who Died, Experienced AEs, Other SAEs or Discontinuations Due to AEs, Drug Related AEs(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With Significant AEs of Special Interest(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total),Protein (Total)(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With MAs in Urinalysis(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Total Number of New SLE Flares Each Participant Experienced(From start of corticosteroid taper to Day 365)
- DB; Median Number of Days to the First Occurrence of a New SLE Flare(From start of corticosteroid taper to confirmation of disease flare or the end of double-blind period)
- DB: Number of Participants With MAs in Serum Chemistry: ALP, AST, ALT, GGT, Bilirubin (Total), BUN and Creatinine(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment(From Day 1 to Day 365)
- DB; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)(Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier)
- OL; Total Number of BILAG A Flares Each Participant Experienced(From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.)
- OL; Area Under the Curve (AUC) for Prednisone or Prednisone Equivalent(From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.)
- DB; Number of Participants With a New SLE Flare During the Initial 6 Months(From start of corticosteroid taper to 6 months.)
- DB; Number of Participants With a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline(From start of study drug treatment to Day 365)
- OL; Number of Participants With a New SLE Flare(From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.)
- OL; Number of Participants With a Change in the SLICC/ACR Damage Index at Year 2 Compared to Baseline(From start of study drug therapy in open-label period (Day 365) and on Day 729.)