| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Adult subjects with active rheumatoid arthritis (RA) according to the American Rheumatism Association criteria for the classification of RA and with inadequate response to methotrexate
|
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
|
| 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 |
| The main objective is to assess the occurrence of early signs of response to abatacept with background methotrexate, as defined by improvement of synovitis measured by Power Doppler Ultrasonography of the affected metacarpophalangeal joints during the study in subjects with active rheumatoid arthritis and inadequate response to methotrexate. |
|
| E.2.2 | Secondary objectives of the trial |
| The second objective is to estimate the predictability of the total PDUS score or its components of the synovitis level of the MCP joints to disease activity measured by DAS28-CRP or DAS28-CRP-derived criteria at specified timepoints during the study. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1)Subjects must meet the 1987 criteria of the American Rheumatism Association
for the classification of RA
2) Subjects must have had a diagnosis of RA for more than 6 months from the time
of the initial diagnosis of RA.
3) Subjects must have disease activity defined by a DAS28-CRP > 3.2, or a tender
joint count of ≥ 6, a swollen joint count of ≥ 6, and a C-reactive protein (CRP)
measurement greater than the upper limit of normal (ULN).
4) Subjects must have a total synovitis PDUS score >1 for at least 3 MCPs at the
screening visit and at the baseline (Day 1, before infusion) visit.
5) Subjects must have been treated with methotrexate of at least 15 mg for at least
3 months before screening and on a stable dose for the last 28 days before the first
dose of abatacept. (Day 1). In subjects with intolerance to methotrexate, the dose
could be reduced to a maximum tolerated dose (ie, 10 mg weekly) for at least
3 months before screening and on a stable dose for the last 28 days before the first
dose of abatacept (Day 1).
6) Subjects who received combination therapy (methotrexate plus another
nonbiologic DMARD) before study entry require washout. These subjects must
not be treated with any background nonbiologic DMARD other than methotrexate
for at least 28 days before treatment (Day 1). In the case of leflunomide, the
washout period is 8 weeks unless subjects take cholestyramine according to the
manufacturer’s recommendation.
7) Subjects who have received oral corticosteroids during the 28 days before
treatment (Day 1) must have been on a stable dose for at least 25 out of 28 days
and on a total dose of ≤ the equivalent of 10 mg prednisone/day.
8) Subjects must be naive to treatment with biologic DMARDs (infliximab,
anakinra, etanercept, adalimumab, rituximab, and any investigational biologic
DMARD). |
|
| E.4 | Principal exclusion criteria |
1)Subjects who are impaired, incapacitated, or incapable of completing studyrelated
assessments.
2) Subjects who meet all diagnostic criteria for any other rheumatic disease (eg,
lupus erythematous).
3) Subjects who underwent previous MCP arthroplasty, have such a procedure
scheduled, or anticipate the need for such a procedure during the study.
4) Subjects with active vasculitis of a major organ system, with the exception of
rheumatoid nodules.
5) Subjects with current symptoms of severe, progressive, or uncontrolled renal,
hepatic, hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, whether or not related to RA and which, in the opinion of the
investigator, might place a subject at unacceptable risk for participation in the
study.
6) Female subjects who have had a breast cancer screening that is suspicious for
malignancy and in whom the possibility of malignancy cannot be reasonably
excluded by additional clinical, laboratory, or other diagnostic evaluations
7) Subjects with a history of cancer in the last 5 years, other than non-melanoma
skin cell cancers cured by local resection or carcinoma in situ. Existing nonmelanoma
skin cell cancers should be removed, the lesion site healed and residual
cancer ruled out before administration of the study drug.
8) Subjects who clinically, significantly abuse drugs or alcohol.
9) 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).
10) Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than
2 months before the informed consent document was signed.
11) Subjects who have received any live vaccines within 3 months of the anticipated
first dose of study medication.
12) Subjects with any serious bacterial infection within the last 3 months, unless
treated and resolved with antibiotics, or any chronic bacterial infection (eg,
chronic pyelonephritis, osteomyelitis or bronchiectasis).
13) Subjects at risk for tuberculosis (TB). Specifically excluded from this study will
be subjects with:
• A history of active TB within the last 3 years, even if it was treated.
• A history of active TB greater than 3 years ago, unless there is
documentation that the prior anti-TB treatment was appropriate in duration
and type.
• Current clinical, radiographic, or laboratory evidence of active TB.
• Latent TB that was not successfully treated (≥ 4 weeks).
14) Subjects must not be positive for hepatitis B surface antigen.
15) Subjects who are positive for hepatitis C antibody if the presence of hepatitis C
virus was also shown with polymerase chain reaction or recombinant immunoblot
assay.
16) Subjects with any of the following laboratory values
• Hemoglobin < 8.5 g/dL
• WBC < 3000/mm3 (< 3 x 109/L)
• Platelets < 100,000/mm3 (< 3 x 109/L)
• Serum creatinine > 2 times the ULN
• Serum ALT or AST > 2 times the ULN
17) Any other laboratory test results that, in the opinion of the investigator, might
place a subject at unacceptable risk for participation in the study.
18) Subjects who have at any time received treatment with any investigational drug
within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1
dose.
19) Subjects who have at any time received treatment with abatacept (BMS-188667
or CTLA4Ig).
20)Women who are pregnant or breastfeeding.
21) Women with a positive pregnancy test on enrollment or before administration of
abatacept. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Study Assessments and Primary Endpoints:
• Efficacy and safety parameters will be assessed at each predefined timepoint: Days 1, 7, 15, 29,
43, 57, 85, 113, 141, 169, and 199.
• Primary efficacy assessments consist of Power Doppler Ultrasonography (PDUS) MCP joint
assessments and the DAS28-CRP. The global PDUS score and DAS28-CRP will be calculated at
all visits during 6 months of treatment.
• Safety will be assessed throughout the study via physical examinations; monitoring of vital signs,
adverse events, and serious adverse events; pregnancy tests; and blood chemistry and hematology
analyses. |
|
| 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 | Yes |
| 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 | No |
| 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 | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 3 |
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