Abatacept in the Treatment and Prevention of Active Systemic Lupus Erythematosus (SLE) Flares in Combination With Prednisone

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00119678

Enrollment

183

Registered

2005-07-14

Start date

2005-09-30

Completion date

2008-11-30

Last updated

2014-09-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Lupus Erythematosus

Keywords

SLE

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.

Interventions

DRUGAbatacept

Injectable, intravenous, 10 mg/kg, abatacept every 28 days, 12 months

DRUGPlacebo

Injectable, intravenous, 0 mg, every 28 days, 12 months

DRUGPrednisone

Tablets, oral, 30 mg, daily for 28 days then taper off, 12 months

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare	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).
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	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	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 Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count	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 Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)	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: Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), Gamma-glutamyl Transferase (GGT), Bilirubin(Total), Blood Urea Nitrogen (BUN), Creatinine	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.
OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)	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 Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides	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.
OL; Number of Participants With MAs in Urinalysis	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.

Secondary

Measure	Time frame	Description
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	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, Sodium (serum): \<0.95\* LLN or \>1.05\* ULN (if pre-Rx \<LLN, then \<0.95\* pre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.05\* pre-Rx or \<LLN); Potassium (serum), Chloride (serum), protein (total): \<0.9\* LLN or \>1.1\* ULN (if pre-Rx \<LLN, then \<0.9\* pre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.1\* pre-Rx or \<LLN; Calcium (total): \<0.8\* LLN or \>1.2\* ULN (if pre-Rx \<LLN, then \<0.75\* pre-Rx or \>ULN. If pre-Rx \>ULN, then \>1.25\* pre-Rx or \<LLN.
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	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, 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.
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	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, RBC, WBC: \>=2+ (or, if value \>=4, or if pre-Rx value = 0 or 0.5, then \>= 2\* pre-Rx, 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; GFR: \<=60 mL/min/1.73m\^2 or \> 15% change from baseline; Protein/creatinine ratio: \> 100 mg/mmol.
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	Vital signs assessments and physical examination were conducted throughout the study. Vital signs assessments included body temperature, respiratory rate, blood pressure (systolic and diastolic) and heart rate. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs or physical examination were clinically meaningful.
DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment	From Day 1 to Day 365	Electrochemiluminescence (ECL) immunoassay based on Meso Scale Discovery (MSD) technology was used to detect antibodies specific for CTLA4-T and for abatacept.
DB; Number of Participants With a New SLE Flare During the Initial 6 Months	From start of corticosteroid taper to 6 months.	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/or 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 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.	SLICC/ACR damage index:measure of cumulative damage due to SLE.Damage=non-reversible change occurring since onset of lupus,ascertained by clinical assessment & present for =\>6 months.Scores of SLICC/ACR index:1:single episode;2:repeated episodes at least 6 months apart.Change in score from baseline to 1 year presented as:no change,increase 1 (an increase in score of 1),increase \>1 (an increase in score of \>1).Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
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.	Total number of BILAG A flares in any organ system after steroid tapering = new BILAG A features in any organ system. Scores defined as follows: None: participants with no BILAG A flare; 1: participants with 1 BILAG A flare or participants who discontinued without a new BILAG A flare were imputed as having one event. 2: participants with 2 BILAG A flares; 3 or \>3: participants with 3 or more BILAG A flares.Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
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.	Total exposure to glucocorticosteroid was measured by the total prednisone or prednisone equivalent AUC. Based on the recommendation of the Data Monitoring Committee, the open-label, long-term extension period was terminated by the sponsor, for failure to meet the primary outcome measure for the double-blind period and because of an increase in SAEs in the abatacept treatment group. As such, these data were not analyzed.
OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment	After the first dose of open-label period	MSD technology was used to detect antibodies specific for CTLA4-T and for abatacept.
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.	SLE flares scored using BILAG:A:presence of =\>1 serious lupus features;B:more moderate features;C:mild symptomatic features;D:prior activity with no current symptoms due to active lupus;E:an organ that has never been involved.BILAG scores based on degrees of change in clinical features (1=improving,2=staying the same,3=worsening,4=new).New SLE flare means new BILAG A/B features in any organ system.Based on the recommendation of the Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.
DB; Total Number of New SLE Flares Each Participant Experienced	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:BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or 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).
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	Elapsed days between start of corticosteroid taper & first day of flare.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/or start of corticosteroid taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).
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	SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity.
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	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. Drug-related AEs: events with a certain; probable; possible; or missing relationship to the study therapy. Participants who discontinued the study due to an AE were recorded.
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	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, AEs of special interest 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.
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	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\* LLN or \>1.5\* ULN (or, if pre-Rx value \<LLN, then \<0.5\* pre-Rx value or \<100000/mm\^3).
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	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. 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.
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	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.

Countries

Australia, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Mexico, Puerto Rico, South Africa, South Korea, Taiwan, United Kingdom, United States

Participant flow

Pre-assignment details

263 participants were enrolled in this study and 80 were excluded from the trial due to screening failure. Of the 183 randomized, 3 were not treated and 5 were treated but excluded due to site closure.

Participants by arm

Arm	Count
Abatacept Participants were administered intravenous (iv) infusions of abatacept (10 mg/kg) over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. All participants received a dose based on screening visit weight. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg once daily (OD). A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant's clinical features qualified for British Isles Lupus Assessment Group (BILAG) C or D status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.	118
Placebo Participants were administered iv infusions of either dextrose 5% solution or normal saline (NS) at a constant rate over approximately 30 minutes on Days 1, 15, 29 and every 28 days thereafter up to and including Day 337. Prednisone or prednisone equivalent was administered at an initial oral dose of 30 mg OD. A standardized prednisone or prednisone equivalent taper procedure was followed whenever the participant's clinical features qualified for BILAG C or D status after Day 29. Participants who completed the double-blind period were eligible for the open-label long-term extension period, where all participants were reallocated to abatacept (regardless of randomized treatment in the double-blind period) according to body weight at study entry. Infusions continued every 28 days until abatacept was marketed for SLE or the drug development program discontinued.	57
Total	175

Withdrawals & dropouts

Period	Reason	FG000	FG001
Double-blind Treatment Period	Adverse Event	7	1
Double-blind Treatment Period	Death	1	0
Double-blind Treatment Period	Lack of Efficacy	21	12
Double-blind Treatment Period	Lost to Follow-up	1	2
Double-blind Treatment Period	Not treated	1	2
Double-blind Treatment Period	Participants not meeting study criteria	0	1
Double-blind Treatment Period	Participant withdrew consent	4	4
Double-blind Treatment Period	Poor/Non-compliance	3	0
Double-blind Treatment Period	Pregnancy	0	2
Double-blind Treatment Period	Site closed due to non-compliance	3	2
Open-label Treatment Period	Administrative reasons by sponsor	87	0
Open-label Treatment Period	Adverse Event	3	0
Open-label Treatment Period	Death	1	0
Open-label Treatment Period	Lack of Efficacy	9	0
Open-label Treatment Period	Lost to Follow-up	3	0
Open-label Treatment Period	Participants not meeting study criteria	2	0
Open-label Treatment Period	Participant withdrew consent	4	0
Open-label Treatment Period	Pregnancy	1	0

Baseline characteristics

Characteristic	Total	Abatacept	Placebo
Age, Continuous	38.0 years	38.0 years FULL_RANGE 12.76	36.0 years
Race/Ethnicity, Customized American Indian/Alaska Native	1 participants	1 participants	0 participants
Race/Ethnicity, Customized Asian	41 participants	28 participants	13 participants
Race/Ethnicity, Customized Black/African American	16 participants	12 participants	4 participants
Race/Ethnicity, Customized Other races	4 participants	3 participants	1 participants
Race/Ethnicity, Customized White	113 participants	74 participants	39 participants
Sex: Female, Male Female	159 Participants	104 Participants	55 Participants
Sex: Female, Male Male	16 Participants	14 Participants	2 Participants
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score Overall SLICC/ACR score 0	120 participants	82 participants	38 participants
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score Overall SLICC/ACR score 1	23 participants	12 participants	11 participants
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score Overall SLICC/ACR score 2	20 participants	15 participants	5 participants
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score Overall SLICC/ACR score >2	7 participants	6 participants	1 participants
Systemic Lupus International Collaborative Clinics/American College of Rheumatology(SLICC/ACC) score Overall SLICC/ACR score unavailable	5 participants	3 participants	2 participants
Weight	68.750 kilograms STANDARD_DEVIATION 17.493	68.630 kilograms STANDARD_DEVIATION 18.717	69.000 kilograms STANDARD_DEVIATION 14.79

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	90 / 121	41 / 59
serious Total, serious adverse events	24 / 121	4 / 59

Outcome results

Primary

Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare

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).

Time frame: From start of corticosteroid taper to Day 365

Population: All randomized and treated participants, grouped by the treatment randomized to (Intent to Treat \[ITT\]). Participants who were inception treatment failures were treated as having 1 new flare; participants who discontinued early without any new flares were treated as having 1 new flare.

Arm	Measure	Value (NUMBER)
Abatacept	Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare	94 Participants
Placebo	Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare	47 Participants

Primary

OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count

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).