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

NCT00119678 | Completed Phase 2 Results

• 1 other identifier: IM101-042
• Study Type: interventional
• Target: 183
• Locations: 14 countries
• Sites: 47

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.

Conditions

Systemic Lupus Erythematosus

Keywords

SLE

Outcome Measures

Primary Outcomes (9)

• 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).

  From start of corticosteroid taper to Day 365

• 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

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• OL; Number of Participants With Significant AEs of Special Interest

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• 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).

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• 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

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides

  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.

  From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

• OL; Number of Participants With MAs in Urinalysis

  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.

  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 (19)

• DB; Number of Participants With a New SLE Flare During the Initial 6 Months

  From start of corticosteroid taper to 6 months.

• 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 a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline

  From start of study drug treatment to Day 365

• 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

Study Arms (3)

Abatacept + Prednisone

ACTIVE COMPARATOR

Double Blind Period

Drug: Abatacept; Drug: Prednisone

Placebo + Prednisone

PLACEBO COMPARATOR

Double Blind Period

Drug: Placebo; Drug: Prednisone

Abatacept

EXPERIMENTAL

Open Label

Drug: Abatacept

Interventions

Abatacept DRUG

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

Also known as: Orencia

Abatacept + Prednisone

Placebo DRUG

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

Placebo + Prednisone

Prednisone DRUG

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

Abatacept + Prednisone; Placebo + Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (52)

University Of Arizona Arthritis Center

Tucson, Arizona, 85724, United States

Location

Office Of Geoffrey S. Dolan, Md

Long Beach, California, 90808, United States

Location

8737 Beverly Blvd.

Los Angeles, California, 90048, United States

Location

Denver Arthritis Clinic

Denver, Colorado, 80230, United States

Location

Cria Research

Fort Lauderdale, Florida, 33334, United States

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The University Of Chicago

Chicago, Illinois, 60637, United States

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Kentuckiana Center For Better Bone And Joint Health

Louisville, Kentucky, 40202, United States

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Kelly, Timothy

Las Vegas, Nevada, 89128, United States

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Suny Downstate Medical Center

Brooklyn, New York, 11203, United States

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Columbia University Medical Center

New York, New York, 10032, United States

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Ok Medical Research Foundations

Oklahoma City, Oklahoma, 73104, United States

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Texas Research Center

Sugarland, Texas, 77479, United States

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Local Institution

Cairns, Queensland, 4870, Australia

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Local Institution

Maroochydore, Queensland, 4558, Australia

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Clayton, Victoria, 3168, Australia

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Heidelberg, Victoria, 3084, Australia

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Malvern, Victoria, 3144, Australia

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Graz, 8036, Austria

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Brussels, 1200, Belgium

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Leuven, 3000, Belgium

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Goiânia, Goiás, 74050, Brazil

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Curitiba, Paraná, 80060, Brazil

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Rio de Janeiro - Rj, Rio de Janeiro, 20551, Brazil

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Campinas, São Paulo, 13083, Brazil

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São Paulo, São Paulo, 01246, Brazil

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São Paulo, São Paulo, 04023900, Brazil

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São Paulo, São Paulo, 04027, Brazil

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São Paulo, São Paulo, 04233, Brazil

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Vancouver, British Columbia, V5Z 1L7, Canada

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Winnipeg, Manitoba, R3A 1M4, Canada

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Bordeaux, 33076, France

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Montpellier, 34295, France

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Paris, 75679, France

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Berlin, 13125, Germany

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Düsseldorf, 40225, Germany

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Freiburg im Breisgau, 79106, Germany

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Ferrara, 44100, Italy

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Aguascalientes, Aguascalientes, 20000, Mexico

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Mexico City, Mexico City, 06726, Mexico

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Morelia, Michioacan, 58070, Mexico

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Ponce, 00716, Puerto Rico

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Berea, KwaZulu-Natal, 4001, South Africa

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Panorama, Western Cape, 7506, South Africa

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Seoul, Sungdong-Gu, 133-792, South Korea

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Seoul, 110-744, South Korea

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Seoul, 137-040, South Korea

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Seoul, 138-736, South Korea

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Kaohsiung City, 833, Taiwan

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Taichung, 407, Taiwan

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Taipei, 105, Taiwan

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Taipei, 11217, Taiwan

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London, Greater London, SE1 7EX, United Kingdom

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Related Publications (3)

• 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.

  PMID: 29534336 DERIVED

• 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.

  PMID: 29214034 DERIVED

• 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.

  PMID: 20533545 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Abatacept; Prednisone

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2005
• First Posted: July 14, 2005
• Study Start: September 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: September 22, 2014
• Results First Posted: May 9, 2011

Record last verified: 2014-09

Locations

AU (1); PR (1); GB (1); ME (3); ZA (2); CA (2); TW (4); DE (3); IT (1); US (12); FR (3); KR (4); BR (8); BE (2)