Phase III Study of BMS-188667 (CTLA4Ig) in Patients With Rheumatoid Arthritis Who Are Currently Failing Anti-TNF Therapy or Who Have Failed Anti-TNF Therapy in the Past.

NCT00048581 | Completed Phase 3 Results

• 1 other identifier: IM101-029
• Study Type: interventional
• Target: 738
• Locations: 1 country
• Sites: 42

Brief Summary

The purpose of this clinical research study is to determine whether abatacept treatment on a background of Disease Modifying Antirheumatic Drugs (DMARDs) will relieve the symptoms of rheumatoid arthritis (RA) in participants who are currently receiving anti-tumor necrosis factor (TNF) therapy for at least 3 months and are not responding or have taken anti-TNF therapy in the last 3 months and did not respond. The safety of treatment with abatacept will also be evaluated. This study also has a 4.5-year long-term extension beginning 6 months after the start of the study.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (8)

• Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169

  ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire (HAQ) score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

  Day 169

• DB; Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ)

  The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  Day 169

• Open-Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.Related AE/SAE=Certain,Probable,Possible,or Missing relationship to Drug

  From first day of OL to 5.5 years

• OL; Number of Participants AEs of Special Interest

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).

  From first day of OL to 5.5 years

• OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria

  Upper Normal Limit (ULN), Lower Normal Limit (LLN), Baseline (BL). Marked abnormality criteria are: Hemoglobin (HGB): \>3 g/dL decrease from BL; Hematocrit: \<0.75 \* BL; Erythrocytes: \<0.75 \* BL; Platelets (PLT): \<0.67 \* LLN/\>1.5 \* ULN, or if BL \< LLN then use 0.5 \* BL/\<100,000 mm\^3; Leukocytes: \<0.75 \* LLN/ \>1.25 \* ULN, or if BL\<LLN then use \<0.8 \* BL/\>ULN, or if BL\>ULN then use \>1.2 \* BL/\<LLN; neutrophils+bands: \<1.0 \* 10\^3 c/uL; eosinophils: \>0.750 \* 10\^3 c/uL; basophils: \> 400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750 \* 10\^3 c/uL/ \>7.50 \* 10\^3 c/uL.

  From first day of OL to 5.5 years

• OL; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality Criteria

  Marked abnormality criteria: Alkaline phosphatase (ALP): \>2\* ULN, or if BL\>ULN then use \>3\* BL; aspartate aminotransferase (AST): \>3\* ULN, or if BL\>ULN then use \>4\* BL; alanine aminotransferase (ALT): \>3\* ULN, or if BL\>ULN then use \>4\* BL; G-Glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN then use \>3\* BL; Bilirubin: \>2\* ULN, or if BL\>ULN then use \>4\* BL; blood urea nitrogen (BUN): \>2\* BL; creatinine: \>1.5\* BL

  From first day of OL to 5.5 years

• OL; Mean Time-matched Baseline Immunoglobulin (Ig) Levels Over the OL

  Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched baseline values were presented by visit and represented the mean baseline value for only that cohort of participants with serum samples available at that visit.

  Baseline and Days 169, 365, 729, and 1093

• OL; Mean Time-matched Change From Baseline in Immunoglobulin (Ig) Levels Over the OL

  Serum samples collected from participants were used to determine serum levels of IgA, IgM, and IgG. Time-matched mean change from baseline = Post-baseline value - time-matched baseline value, where the time-matched baseline value represents the mean baseline value for only that cohort of participants with serum samples available at that visit.

  BL, Days 169, 365, 729, and 1093

Secondary Outcomes (75)

• DB; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time

  Days 15, 29, 57, 85, 113, 141, and 169

• DB; Mean Time-matched Baseline Tender Joint Counts (TJCs) and Post-Baseline TJCs Over Time: ACR Core Component

  BL

• DB; Mean Time-Matched Percentage of Change From Baseline in TJC Over Time: ACR Core Component

  BL, Days 15, 29, 57, 85, 113, 141, and 169

• DB; Mean Time-matched Baseline Swollen Joint Count (SJC) and Post-Baseline SJCs Over Time: ACR Core Component

  Days 15, 29, 57, 85, 113, 141, and 169

• DB; Mean Time-Matched Percentage of Change From Baseline in SJC Over Time: ACR Core Component

  Days 15, 29, 57, 85, 113, 141, and 169

Study Arms (3)

Abatacept

ACTIVE COMPARATOR

Short Term Portion of Study

Drug: Abatacept

Placebo

PLACEBO COMPARATOR

Short Term Portion of Study

Drug: Placebo

Abatacept (Long Term)

ACTIVE COMPARATOR

Long Term Portion of Study: All participants receive Active Drug

Drug: Abatacept

Interventions

Abatacept DRUG

Vials, intravenous (IV), \~10mg/kg abatacept, One every 2 weeks for first month then every 4 weeks thereafter, 6 months.

Also known as: Orencia, BMS-188667, CTLA4Ig

Abatacept

Placebo DRUG

Vials, IV, 0mg, One every 2 weeks for first month then every 4 weeks thereafter, 6 months.

Placebo

Eligibility Criteria

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

You may not qualify if:

• Women who are pregnant or breast feeding
• Current symptoms of serious medical disease
• History of cancer in last 5 years other than non-melanoma skin cancer
• Chronic serious infection
• Active TB requiring treatment in last 5 years
• Herpes zoster in last 2 months
• Any active viral infection including Human Immunodeficiency Virus (HIV)
• Serious side effects associated with previous anti-TNF therapy

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (42)

Local Institution

Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Paradise Valley, Arizona, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Palo Alto, California, United States

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Rancho Mirage, California, United States

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Denver, Colorado, United States

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Englewood, Colorado, United States

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Bridgeport, Connecticut, United States

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Hamden, Connecticut, United States

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Clearwater, Florida, United States

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Fort Lauderdale, Florida, United States

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Largo, Florida, United States

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Palm Harbor, Florida, United States

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Tampa, Florida, United States

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Rome, Georgia, United States

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Indianapolis, Indiana, United States

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Wichita, Kansas, United States

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New Orleans, Louisiana, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Lincoln, Nebraska, United States

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New Brunswick, New Jersey, United States

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Albany, New York, United States

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Syracuse, New York, United States

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Charlotte, North Carolina, United States

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Hickory, North Carolina, United States

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Bismarck, North Dakota, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Portland, Oregon, United States

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Duncansville, Pennsylvania, United States

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Norristown, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Willow Grove, Pennsylvania, United States

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Charleston, South Carolina, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Vancouver, Washington, United States

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Milwaukee, Wisconsin, United States

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Related Publications (4)

• Hassett AL, Li T, Buyske S, Savage SV, Gignac MA. The multi-faceted assessment of independence in patients with rheumatoid arthritis: preliminary validation from the ATTAIN study. Curr Med Res Opin. 2008 May;24(5):1443-53. doi: 10.1185/030079908x297376. Epub 2008 Apr 9.

  PMID: 18402714 BACKGROUND

• Stewart AL and Ware JE. Measuring function and well being. The Medical Outcomes Study Approach. Durham, NC: Duke University Press. 1992.

  BACKGROUND

• Spritzer KL, Hays RD. (2003, November). MOS Sleep Scale: A Manual For Use and Scoring, Version 1.0. Los Angeles, CA.

  BACKGROUND

• Alten R, Burkhardt H, Feist E, Kruger K, Rech J, Rubbert-Roth A, Voll RE, Elbez Y, Rauch C. Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting. Arthritis Res Ther. 2018 Jan 2;20(1):1. doi: 10.1186/s13075-017-1488-5.

  PMID: 29329602 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; 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

Results Point of Contact

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

Clinical.Trials@bms.com

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2002
• First Posted: November 13, 2002
• Study Start: December 1, 2002
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: November 21, 2011
• Results First Posted: June 23, 2011

Record last verified: 2011-11

Locations

US (42)