Abatacept With Methotrexate- Phase IIB

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00162266
• Date of registration: 09/09/2005
• Prospective Registration: No
• Primary sponsor: Bristol-Myers Squibb
• Public title: Abatacept With Methotrexate- Phase IIB
• Scientific title: A Phase IIB, Multi-Center, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Clinical Efficacy of Two Different Doses of BMS-188667 Administered Intravenously to Subjects With Active Rheumatoid Arthritis While Receiving Methotrexate
• Date of first enrolment: October 2000
• Target sample size: 524
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00162266
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Belgium, Canada, France, Germany, Ireland, Netherlands, South Africa, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion criteria

Inclusion Criteria:

Double blind study phase:

1. Males or females (not nursing and not pregnant), at least 18 years of age. Women of
child bearing potential (WOCBP) are eligible if they are practicing effective
contraceptive measures

2. Subjects must meet the criteria of the American Rheumatism Association (1987) for the
diagnosis of rheumatoid arthritis and the American College of Rheumatology (1991)
functional classes I, II, or III

3. Subjects have been taking Methotrexate (10-30 mg weekly) for at least 6 months, and at
a stable dose for 28 days prior to treatment

4. Washout/drug stabilization requirements (except Methotrexate) [Informed consent must
be signed before making any changes in RA therapy if those changes are solely for the
purpose of this study].

- Leflunomide or Infliximab have already been discontinued at least 60 days prior
to enrollment (prior to signing of informed consent) and a total of 90 days prior
to treatment. All other Disease Modifying Anti-Rheumatic Drugs (DMARDs) (except
Methotrexate) have been withdrawn at least 28 days prior to treatment

- Oral corticosteroid treatment has been reduced to the equivalent of 10 mg or less
prednisone daily and stabilized for at least 28 days prior to enrollment

5. Eligibility of subjects for the study is based on their disease activity and
anti-rheumatic treatment at the initial visit:

- Methotrexate monotherapy: Subject is receiving only Methotrexate, steroids,
Non-steroidal anti-inflammatory drugs (NSAIDs) and will not require washout

- Combination therapy: Subject is receiving Methotrexate in combination with
another DMARD(s) and will require washout

At entry, Methotrexate monotherapy must have a disease activity:

- 10 or more swollen joints (66 joint count)

- 12 or more tender joints (68 joint count)

- C reactive protein (CRP) =.1 mg/dL (10 mg/L) at "Screening" visit

At entry, combination therapy must have a disease activity (if subject does not
satisfy the above):

- 6 or more swollen joints (66 joint count)

- 8 or more tender joints (68 joint count)

- No restriction on C-reactive protein (CRP)

In addition

All subjects who were on combination therapy at entry must undergo a 28 day washout
period of DMARDs other than Methotrexate. After the washout/drug stabilization and
prior to randomization such subjects must have:

- 10 or more swollen joints (66 joint count)

- 12 or more tender joints (68 joint count)

- C reactive protein (CRP) = 1 mg/dL (10 mg/L)

6. Subject is willing to participate in the study and willing to sign the informed
consent

Open label study phase:

- Participants that have completed the initial short term portion (double blind) of the
study

Exclusion Criteria:

Double blind study phase:

1. Subjects who have at any time received treatment with BMS-188667 (Abatacept)

2. Subjects who within 30 days of the Day 1 visit have received treatment with any
investigational drug

3. Subjects with active vasculitis of a major organ system (except for subcutaneous
rheumatoid nodules)

4. Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral
disease. Concomitant medical conditions that in the opinion of the investigator might
place the subject at unacceptable risk for participation in this study

5. Mammogram requiring further investigation or biopsies leading to the diagnosis of a
clinically significant abnormality. Complete evaluation of lesion is required before
initiation of dosing

6. Subjects with a history of cancer within the last five years (other than non-melanoma
skin cell cancers cured by local resection)

7. Subjects who have a history of clinically significant drug or alcohol abuse, or admit
to consumption of more than 1 alcoholic drink per day

8. Subjects with evidence (as assessed by the investigator) of active or latent bacterial
or viral infections at the time of potential enrollment, including subjects with
evidence of Human Immunodeficiency Virus (HIV) infection, or hepatitis B or C
infection

9. Subjects with any serious or chronic infections such as pneumonia, pyelo-nephritis,
renal infection, chest infection with bronchiectasis, or sinusitis in the previous 3
months

10. Subjects with active tuberculosis requiring treatment within the previous 3 years

11. Subjects with any opportunistic infections such as herpes zoster or cytomegalovirus
(CMV) within the previous 2 months

12. Subjects with severe asthma defined as > 3 emergency room admissions in the last year
or > 3 treatments with oral steroids for asthma in the last year

13. A history of either angioedema or anaphylaxis that was associated with a reaction to a
drug

14. Subjects with the following laboratory values:

- Hemoglobin < 8.5 g/dL

- White blood cells < 3000/mm3

- Platelets < 100,000/mm3

- Serum creatinine > 2 times upper limit of normal

- Serum Alanine aminotransferase (ALAT) or Aspartate aminotransferase (ASAT) > 2
times upper limit of normal

- Any other lab values that in the opinion of the investigator might place the
subject at unacceptable risk for participation in this study

Open label study phase:

- Participants must continue to meet inclusion/exclusion criteria as in the short term
(double blind) phase of the protocol except subjects who have receiving other than
Abatacept



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Abatacept (BMS-188667)

Drug: Placebo

Primary Outcome(s)

Baseline Serum Immunoglobulin A (IgA) Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720,1080, 1440, and 1800]

Mean Change From Baseline (BL) in IgA Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800]

Number of Participants With Electrolyte Values Meeting Marked Abnormality Criteria in OL Period [Time Frame: Day 360 to Day 3060]

Number of Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting Marked Abnormality Criteria in OL Period [Time Frame: Day 360 to Day 3060]

Number of Participants With Hematology Values Meeting Marked Abnormality Criteria in OL Period [Time Frame: Day 360 to Day 3060]

Number of Participants With Liver and Kidney Function Values Meeting Marked Abnormality Criteria in OL Period [Time Frame: Day 360 to Day 3060]

Mean Change From Baseline (BL) in IgG Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800]

Mean Change From Baseline (BL) in IgM in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800]

Number of Participants With AEs of Special Interest in OL Period [Time Frame: Day 360 to Day 3060]

Baseline Immunoglobulin G (IgG) Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440 and 1800]

Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) in OL Period [Time Frame: Day 360 to Day 3060]

Baseline Immunoglobulin M (IgM) Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720,1080,1440, and 1800]

Number of Responders to American College of Rheumatology 20% Improvement Criteria (ACR 20) at Day 180 of the Double-Blind (DB) Period [Time Frame: Day 180]

Participants Receiving Concomitant Disease Modifying Rheumatic Drugs and Biologics in Open-Label (OL) Period [Time Frame: Day 360 to Day 3,060]

Secondary Outcome(s)

ACR Numeric Values (ACR-N) [Time Frame: Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360]

Individual Components of ACR Criteria--Mean Percentage Change From Baseline at Day 180 [Time Frame: Baseline, Day 180]

Mean Baseline Vitality Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Change From Baseline in Level of C Reactive Protein Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, 3060]

Mean Change From Baseline in sIL2-r Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800]

Adjusted Mean Percent Changes From Baseline in the Modified Health Assessment Questionnaire (mHAQ) at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Number of ACR 70 Responders in DB Period [Time Frame: Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360]

Immunogenicity Data: Categories of Post Baseline Value to Baseline Value (VA/PRE) Ratios and Number of Participants With Sero-conversion (Anti-CTLA4Ig Antibodies With IG Region) [Time Frame: Baseline, Days 30, 90, 180, 270, 360]

Pharmacodynamic Measure: Mean Changes From Baseline in Tumor Necrosis Factor (TNF)-Alpha at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Immunogenicity Data: Anti-CTLA4Ig Antibodies Without IG Region [Time Frame: Baseline, Days 30, 90, 180, 270, 360]

Mean Baseline (BL) Physical Functioning Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Baseline Role-Emotional Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Baseline Mental Health Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Baseline Bodily Pain Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

ACR-N Area Under The Curve (AUC) on Day 180 and Day 360 [Time Frame: Baseline and Day 180; Baseline and Day 360]

Immunogenicity Data: Anti-CTLA4Ig Antibodies With Immunoglobulin (IG) Region [Time Frame: Baseline, Days 30, 90, 180, 270, 360]

Mean Baseline Role-Physical Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Baseline Level of Serum Rheumatoid Factor Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720,1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Immunogenicity Data: Categories of Post Baseline Value to Baseline Value (VA/PRE) Ratios and Number of Participants With Sero-conversion(Anti-CTLA4Ig Antibodies Without IG Region) [Time Frame: Baseline, Days 30, 90, 180, 270, 360]

Mean BL General Health Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Baseline Soluble Serum Interleukin-2 Receptor Level (sIL2-r) Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720,1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Individual Components of ACR Criteria--Mean Percentage Change From Baseline at Day 360 [Time Frame: Baseline, Day 360]

Mean Baseline Physical Component Summary (PCS) of the Short-Form 36 (SF-36) Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2880, and 3060]

Number of Participants Who Discontinued Due to Lack of Efficacy in the DB and OL Periods [Time Frame: Day 1 to Day 360 (Double-Blind Period), Day 361 to Day 3060 (Open-Label Period)]

Mean Changes From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Number of ACR 50 Responders in DB Period [Time Frame: Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360]

Mean Baseline Social Functioning Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Number of ACR 50 Responders in the OL Period [Time Frame: Days 360, 450, 540, 630, 720, 810, 900, 1080, 1350, 1440, 1530, 1620, 1710, 1800, 1980, 2160, 2340, 2520, 2700, 2880, and 3060]

Mean Change From Baseline (BL) in the Role-Emotional Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Pharmacodynamic Measure: Mean Changes From Baseline in E-Selectin at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Mean Change From Baseline (BL) in the General Health Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Change From Baseline (BL) in the Mental Health Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Change From Baseline (BL) in the Vitality Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Pharmacodynamic Measure: Mean Changes From Baseline in Plasma Soluble Interleukin-2 Receptor (sIL-2R) at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Mean Change From Baseline in Serum Rheumatoid Factor Level Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720,1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Mean Change From Baseline (BL) in the Physical Functioning Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Pharmacodynamic Measure: Mean Changes From Baseline in Interleukin-6 at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Mean Change From BL in the Bodily Pain Domain of the SF-36 Over Time in OL Period [Time Frame: BL (Day 0); Day 360; Day 720; Day 1,080; Day 1,440; Day 1,800; Day 2,160; Day 2,520; Day 2,880; Day 3,060]

Pharmacodynamic Measure: Mean Changes From Baseline in Rheumatoid Factor at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Mean Change From Baseline (BL) in the Social Functioning Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Number of Participants With At Least One New Active Joint (Tender Joints and Swollen Joints) at Day 180 and Day 360 [Time Frame: Day 180, Day 360]

Number of ACR 20 Responders in DB Period [Time Frame: Days 15, 30, 60, 90, 120, 150,180, 240, 300, and 360]

Number of Participants With a Clinically Meaningful Improvement on the Modified Health Assessment Questionnaire (mHAQ) in OL Period [Time Frame: Days 360, 720,1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Participants With Laboratory Abnormalities Meeting the Marked Abnormality Criteria for Selected Blood Chemistry Values During Double-Blind Therapy [Time Frame: From the start of study up to 60 days post the end of the 12-month double-blind period]

Mean Baseline Mental Component Summary (MCS) of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2880, and 3060]

Mean Baseline Serum C-Reactive Protein Level Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080,1440,1800, 2160, 2520, 2880, 3060]

Mean Change From Baseline (BL) in the MCS of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 450, 540, 630, 720, 810, 900, 1080, 1350, 1440, 1530, 1620, 1710, 1800, 1980, 2160, 2340, 2520, 2700, 2880, and 3060]

Mean Change From Baseline (BL) in the Physical Component Summary (PCS) of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2880, and 3060]

Mean Change From Baseline (BL) in the Role-Physical Domain of the SF-36 Over Time in OL Period [Time Frame: Baseline (Day 0) and Days 360, 720, 1080, 1440, 1800, 2160, 2520, 2880, and 3060]

Number of ACR 20 Responders in OL Period [Time Frame: Days 360, 450, 540, 630, 720, 810, 900, 1080, 1350, 1440, 1530, 1620, 1710, 1800, 1980, 2160, 2340, 2520, 2700, 2880, and 3060]

Number of ACR 70 Responders in the OL Period [Time Frame: Days 360, 450, 540, 630, 720, 810, 900, 1080, 1350, 1440, 1530, 1620, 1710, 1800, 1980, 2160, 2340, 2520, 2700, 2880, and 3060]

Participants Who Experienced Death, Adverse Events (AEs), Serious AEs (SAEs), and Discontinuations During the Double-Blind Period [Time Frame: From the start of study through the end of the double-blind period (at 12 months)]

Participants With Laboratory Abnormalities Meeting the Marked Abnormality Criteria for Selected Hematologic Values During Double-Blind Therapy [Time Frame: From the start of study up to 60 days post the end of the 12-month double-blind period]

Pharmacodynamic Measure: Mean Changes From Baseline in Soluble Inter-Cellular Adhesion Molecule 1 (sICAM-1) at Day 180 and Day 360 [Time Frame: Baseline, Day 180, Day 360]

Secondary ID(s)

IM101-100

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 01/06/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00162266