RHEUMATOID ARTHRITIS,NOS
Conditions
Interventions
Product Name: Abatacept
Product Code: BMS-188667
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Abatacept
C
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) 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. (see Appendices 1 and 2 of the protocol) 2) Rheumatoid Arthritis for greater than 1 year from the time of the initial diagnosis of RA. 3) Subjects with RA who are currently receiving or previously received an anti-TNF therapy at an approved labeled dose for at least 3 months, but had in the investigator’s opinion, an inadequate efficacy response to therapy. Subjects who discontinue or discontinued an anti-TNF therapy due to intolerance or safety will be considered as anti-TNF therapy failures at any time point after they have received their first dose of anti-TNF therapy. 4) Men and women (not nursing and not pregnant) at least 18 years of age. Women of child bearing potential are eligible if they are practicing effective contraceptive measures. -Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 10 weeks after the last infusion of abatacept in such a manner that the risk of pregnancy is minimized. -WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 48 hours prior to the start of study medication. 5) Drug stabilization requirements: a) Subjects must be on one or more background non-biologic DMARD(s) at a stable dose for a 28 day period prior to treatment (Day 1). b) Oral corticosteroid treatment must be stabilized for at least 25 out of 28 days prior to treatment, (Day 1). 6) Subjects must have a qualifying DAS28 >= 5.1. Subjects who have a DAS28 >= 4.8 but =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Women who are pregnant or breastfeeding. 2) Women with a positive pregnancy test on enrollment or prior to start of study drug administration. 3) WOCBP using a prohibited contraceptive method (there are none). 4) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 10 weeks after the last infusion of study medication. 5) Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules). 6) Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, ophthalmologic 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. 7) Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. 8) Subjects who have a history of clinically significant drug or alcohol abuse. Subjects currently taking methotrexate or leflunomide who admit to consumption of more than an average of 1 alcoholic drink per day. 9) Subjects with any serious bacterial infection (such as pneumonia, other renal infection and sinusitis), unless treated and resolved with antibiotics or chronic bacterial infection (such as pyelonephritis and chest infection with bronchiectasis) in the previous 3 months. 10) Subjects with active tuberculosis requiring treatment within the previous 3 years. Subjects with a positive PPD at screening will not be eligible for the study unless they completed treatment for latent TB and have a negative chest x-ray at enrollment. 11) Subjects with herpes zoster that resolved less than 2 months prior to enrollment. 12) 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. 13) Significant toxicities associated with concomitant DMARD therapy or previous anti-TNF therapy that would preclude subjects from participating and completing the study. 14) Subjects with repeated (at least 2) serious infections (such as pneumonia, other renal infections, sinusitis) requiring intravenous therapy while on anti-TNF therapy. 15) Subjects with a history of severe allergic reaction(s) to Anti- TNF therapy. 16) Subjects with any of the following laboratory values: • Hgb 2 times upper limit of normal. • Serum ALT or AST > 2 times upper limit of normal. • Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Summarize incidence of adverse events/serious adverse events/discontinuations due to adverse events during 6 months of combined treatment with abatacept and 1 or more background non-biologic DMARDs approved for RA in subjects with active RA Long-Term Extension(Amdt 5) Assess long-term safety + tolerability of abatacept in subjects that completed the initial 6-month open-label treatment period. This amendment also allows continuous safety monitoring of abatacept ; Secondary Objective: Assess: -incidence of adverse events/serious adverse events/discontinuations between current and previous users -% subjects achieving clinically meaningful improvement in DAS28(reduction of at least 1.2 units) at Day 169(Month 6) -% subjects achieving Low Disease Activity(DAS28 =< 3.2) at Day 169 -% subjects achieving remission(DAS28 < 2.6) at Day 169 -disease activity as measured by Disease Activity Score-28(DAS28) over time -safety of chronic use of abatacept -discontinuation rate in subjects receiving abatacept -abatacept immunogenicity -changes in surrogate markers(hs-CRP, RF) in subjects receiving abatacept -improvement in physical functioning(HAQ) and in SF36 at Day 169 -reduction in fatigue using Fatigue VAS at Day 169 Long-Term Extension(Amdt 5) Assess: -abatacept efficacy+immunogenicity in combination with nonbiologic background DMARDs -maintenance of response in subjects who eliminate/reduce their dose of concomitant nonbiologic background DMARD therapy ;Primary end point(s): Physical examination findings, vital signs, laboratory test results and adverse events will be evaluated during the course of the study. Clinical response will be evaluated by the | — |
Countries
Belgium, Czech Republic, Germany, Ireland, Italy, Spain, United Kingdom
Outcome results
None listed