| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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
|
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 < 5.1 at screening, will be allowed to
repeat the Tender and Swollen Joint Count and the subject’s assessment of disease
activity (VAS) in order to reassess eligibility. These assessments may be repeated
only once and must be completed within 2 weeks of the initial screening visit. The
hs-CRP component may not be repeated.
Long-Term Extension (Amendment 5)
Subjects must continue to meet Inclusion/Exclusion criteria as outlined in Protocol
IM101064 and/or all subsequent amendments, with the exception of the DAS 28 entry requirement or the requirement to be receiving a stable dose of a non-biologic DMARD. |
|
| E.4 | Principal 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 < 8.5 g/dL.
• WBC < 3,000/mm3 (3 x 109/L).
• Platelets < 100,000/mm3 (100 x 109/L).
• Serum creatinine > 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.
17) Subjects previously treated with rituximab: B cell levels are less than lower limit of normal as measured by Fluorescent Activated Cell Sorting (FACS) analysis.
18) Subjects who have at any time received treatment with BMS-188667, CTLA4Ig or
abatacept.
19) Subjects who have received treatment with any investigational drug within 28 days of the Day 1 dose.
20) Subjects currently receiving treatment with mycophenolate mofetil (CellCept),
cyclosporine and d-penicillamine or calcineurin inhibitors.
21) Subjects who have received treatment with rituximab less than 12 months prior to screening.
22) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study. |
|
| E.5 End points |
| E.5.1 | 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 Disease Activity Score (DAS28) criteria. The DAS28 measures the current RA disease activity. The variables used to calculate the DAS28 include the number of swollen and tender joints using 28-joint counts, hs-CRP (measured in mg/L), the subject global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm. Other responses (e.g.HAQ) outcome measures (e.g., SF-36), physician’s global assessment of disease activity will also be evaluated. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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