A Phase 3B, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination with Methotrexate Compared to Methotrexate Monotherapy in Achieving Clinical Remission in Adults with Early Rheumatoid Arthritis who are Methotrexate Naive
- Conditions
- Rheumatoid Arthritis10003816
- Registration Number
- NL-OMON43711
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 24
1. Subjects that have early RA as defined as:
- Diagnosis made by the ACR/EULAR 2010 criteria for the classification of RA
- Diagnosis made within the past 6 months;2. Subjects must meet at least one of the following criteria:
- CRP greater than 0.3 mg/dL (ULN)
- ESR greater than or equal to 28 mm/h;3. Subjects that have at least 3 tender joints and at least 3 swollen joints using the 28 Joint Count Assessment at both screening and Day 1;4. Subjects are positive for anti-citrullinated protein antibodies (ACPA);5. Subjects receiving oral corticosteroids must be on a stable dose and at the equivalent of less than or equal to 10 mg prednisone daily for at least 4 weeks.;6. Men and women aged more than 18 years old;7. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug; must not be breastfeeding; agree to follow instructions for methods of contraception for the duration of treatment with study drug plus a total of 100 days post-treatment completion.;8. Men who are sexually active with WOCBP must agree to follow instructions for methods of contraception for the duration of treatment with study drug plus 160 days post-treatment completion.;9. At a minimum, subjects must agree to use of two methods of contraception, with one method
being highly effective and the other method being either highly effective or less effective as
listed in the protocol.
1. Target Disease Exceptions
a) Subjects with autoimmune disease other than RA (eg, SLE, Juvenile Idiopathic Arthritis, vasculitis, seronegative spondyloarthritis, Inflammatory Bowel Disease). However, subjects with secondary Sjogren*s syndrome will be allowed.
b) Prior history of or current inflammatory joint disease other than RA (such as, systemic lupus erythematosus, gout, reactive arthritis, Lyme disease)
c) Subjects with active fibromyalgia
d) Subjects who have a history of Felty*s Syndrome;2. Medical History and Concurrent Diseases
a) Subjects at risk for tuberculosis (TB) defined as follows:
i) Current clinical, radiographic or laboratory evidence of active TB. Chest x-rays (PA and lateral) obtained within the 6 months prior to randomisation will be permitted. TB testing (interferon gamma release assay or PPD) performed in the past month prior to randomisation will be accepted.
ii) A history of active TB unless there is documentation that the subject had received prior anti-TB treatment that was appropriate in duration and type.
iii) Subjects with a positive TB screening test indicative of latent TB will not be eligible for the study unless they have no evidence of current TB on chest x-ray at screening and they are actively being treated for TB with isoniazid (INH) or other therapy for latent TB given according to local health authority guidelines. If permitted by local guidelines regarding treatment with biologic medications, subjects may be randomised prior to completion of treatment as long as they have completed at least 4 weeks of treatment and they have no evidence of current TB on chest x-ray at screening.;b) Subjects with recent acute infection defined as:
i) Any acute infection within 60 days prior to randomisation that required hospitalisation or treatment with parenteral antibiotics
ii) Any acute infection within 30 days prior to randomisation that required oral antimicrobial or antiviral therapy;c) Subjects with history of chronic or recurrent bacterial infection (such as chronic pyelonephritis, osteomyelitis, and bronchiectasis) or serious latent viral infections at the time of enrollment, including subjects with evidence of Immunodeficiency Virus (HIV) infection.;d) Subjects with any history of infection of a joint prosthesis or artificial joint.;e) Subjects who have a history of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis);f) Subjects with history of recurrent herpes zoster (more than 1 episode) or disseminated (more than 1 dermatome) herpes zoster or disseminated herpes simplex, or ophthalmic zoster will be excluded. Symptoms of herpes zoster or herpes simplex must have resolved more than 60 days prior to screening;g) Subjects with history of primary or secondary immunodeficiency or a family history of a
primary immune deficiency in a first degree relative.;h) Subjects who have present or previous malignancies, except documented history of cured non-metastatic squamous or basal skin cell carcinoma, or cervical carcinoma in situ, with no recurrence in the 5 years prior to screening. Subjects who had screening procedure that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations;i) Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy endpoint is the proportion of subjects in SDAI Remission<br /><br>at Week 24.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints below will be assessed in the order below in a<br /><br>hierarchical fashion after the primary endpoint is met to preserve the type I<br /><br>error of the study at 5%<br /><br>(1) Proportion of subjects in DA28-CRP Remission at Week 24<br /><br>(2) Proportion of subjects in SDAI Remission at Week 52<br /><br>(3) Mean change from baseline in TSS at Week 52<br /><br>(4) Proportion of subjects in Boolean Remission at Week 52</p><br>