Clinical trial NCT00119678: Abatacept in the Treatment and Prevention of Active Systemic Lupus Erythematosus (SLE) Flares in Combination With Prednisone
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-07-14
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare
timeFrame: From start of corticosteroid taper to Day 365
measure: 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
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With Significant AEs of Special Interest
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: 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
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
measure: OL; Number of Participants With MAs in Urinalysis
timeFrame: From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
Secondary outcomes:
measure: DB; Number of Participants With a New SLE Flare During the Initial 6 Months
timeFrame: From start of corticosteroid taper to 6 months.
measure: DB; Total Number of New SLE Flares Each Participant Experienced
timeFrame: From start of corticosteroid taper to Day 365
measure: DB; Median Number of Days to the First Occurrence of a New SLE Flare
timeFrame: From start of corticosteroid taper to confirmation of disease flare or the end of double-blind period
measure: DB; Number of Participants With a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline
timeFrame: From start of study drug treatment to Day 365
measure: DB; Number of Participants Who Died, Experienced AEs, Other SAEs or Discontinuations Due to AEs, Drug Related AEs
timeFrame: 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
measure: DB; Number of Participants With Significant AEs of Special Interest
timeFrame: 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
measure: DB; Number of Participants With MAs in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count
timeFrame: 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
measure: DB; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
timeFrame: 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
measure: DB: Number of Participants With MAs in Serum Chemistry: ALP, AST, ALT, GGT, Bilirubin (Total), BUN and Creatinine
timeFrame: 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
measure: DB; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total),Protein (Total)
timeFrame: 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
measure: DB; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides
timeFrame: 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
measure: DB; Number of Participants With MAs in Urinalysis
timeFrame: 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
measure: DB; Number of Participants With Clinically Significant Abnormal Vital Signs and/or Physical Examination Findings
timeFrame: 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
measure: DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment
timeFrame: From Day 1 to Day 365
measure: OL; Number of Participants With a New SLE Flare
timeFrame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
measure: OL; Number of Participants With a Change in the SLICC/ACR Damage Index at Year 2 Compared to Baseline
timeFrame: From start of study drug therapy in open-label period (Day 365) and on Day 729.
measure: OL; Total Number of BILAG A Flares Each Participant Experienced
timeFrame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
measure: OL; Area Under the Curve (AUC) for Prednisone or Prednisone Equivalent
timeFrame: From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
measure: OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment
timeFrame: After the first dose of open-label period
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University Of Arizona Arthritis Center
state: Arizona
city: Long Beach
country: United States
facility: Office Of Geoffrey S. Dolan, Md
state: California
city: Los Angeles
country: United States
facility: 8737 Beverly Blvd.
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Ft. Lauderdale
country: United States
facility: Cria Research
state: Florida
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Louisville
country: United States
facility: Kentuckiana Center For Better Bone And Joint Health
state: Kentucky
city: Las Vegas
country: United States
facility: Kelly, Timothy
state: Nevada
city: Brooklyn
country: United States
facility: Suny Downstate Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Oklahoma City
country: United States
facility: Ok Medical Research Foundations
state: Oklahoma
city: Sugarland
country: United States
facility: Texas Research Center
state: Texas
city: Cairns
country: Australia
facility: Local Institution
state: Queensland
city: Maroochydore
country: Australia
facility: Local Institution
state: Queensland
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: Graz
country: Austria
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Rio De Janeiro - Rj
country: Brazil
facility: Local Institution
state: Rio De Janeiro
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: São Paulo
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Bordeaux Cedex
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Duesseldorf
country: Germany
facility: Local Institution
city: Freiburg
country: Germany
facility: Local Institution
city: Ferrara
country: Italy
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
state: Sungdong-Gu
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Mexico City
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Morelia
country: Mexico
facility: Local Institution
state: Michioacan
city: Aguascalientes
country: Mexico
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Berea
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Hu Y, Carman JA, Holloway D, Kansal S, Fan L, Goldstine C, Lee D, Somerville JE, Latek R, Townsend R, Johnsen A, Connolly S, Bandyopadhyay S, Shadick N, Weinblatt ME, Furie R, Nadler SG. Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids. Arthritis Rheumatol. 2018 Aug;70(8):1331-1342. doi: 10.1002/art.40476. Epub 2018 Jul 12.
citation: Bandyopadhyay S, Connolly SE, Jabado O, Ye J, Kelly S, Maldonado MA, Westhovens R, Nash P, Merrill JT, Townsend RM. Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial. Lupus Sci Med. 2017 Jul 28;4(1):e000206. doi: 10.1136/lupus-2017-000206. eCollection 2017.
citation: Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D'Cruz D, Wallace DJ, Bae SC, Sigal L, Becker JC, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2010 Oct;62(10):3077-87. doi: 10.1002/art.27601.