Randomized, Parallel, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of SBI-087 in Seropositive Subjects With Active Rheumatoid Arthritis on a Stable Background of Methotrexate
- Conditions
- Rheumatoid arthritis (seropositive)MedDRA version: 9.1Level: LLTClassification code 10040107Term: Seropositive rheumatoid arthritis
- Registration Number
- EUCTR2009-010516-15-HU
- Lead Sponsor
- Wyeth Research Division of Wyeth Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
1.Age =18 years at the time of the signing of the ICF (or older as required by local regulation or ethics committees).
2.Subjects must be able to comply with all the requirements of the study.
3.Women of childbearing potential (WOCBP) must have a negative urine pregnancy test at screening and baseline. WOCBP are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Women of non-childbearing potential are defined as either postmenopausal (history of amenorrhea for =52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed =1 year before screening). This information must be documented in the subject’s source documents.
4.WOCBP must agree and commit to the use of hormonal contraception, double-barrier contraception, or an intrauterine device throughout the entire study (defined as the time of the signing of the ICF through the conclusion of subject participation). Double-barrier contraception is defined as the use of a diaphragm, condom, or cervical cap plus a spermicidal vaginal foam, cream, jelly, suppository, or sponge. WOCBP who have a vasectomized partner are also eligible for participation. Vasectomized partners must have had their vasectomy more than 6 months before study day 1.
5.Men must agree and commit to use a medically acceptable form of contraception for the entire study (defined as the time of the signing of the ICF through the conclusion of subject participation) unless surgically sterile. Medically acceptable forms of contraception include properly used barrier forms of contraception.
6.Meets the American Rheumatism Association 1987 revised criteria for classification of RA at least 6 months prior to screening.
7.ACR functional class I through III.
8.At screening, active RA consisting of =5 swollen and =5 tender joints (28-joint count) and 1 or both of the following:
•C-reactive protein (CRP) =10 mg/L
•Erythrocyte sedimentation rate (ESR) =28 mm/h
9.Must be seropositive as defined by a documented history of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) positivity. If a documented history of RF or anti-CCP positivity is not available, RF and anti-CCP titers will be obtained at screening.
10.Must be receiving a MTX regimen (up to 25 mg weekly), according to standard medical practice and local regulation for at least 12 weeks prior to baseline with or without a prior history of TNF use. The dose and route of administration of MTX must be stable for at least 8 weeks prior to baseline.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Pregnant women, nursing mothers, or women planning to become pregnant during the study.
2.Any cardiovascular, neurological, metabolic, immunological, hepatic, or renal condition that, in the opinion of the investigator, could be detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or important concurrent medical events.
3.Presence of active or suspected latent infection including any underlying diseases including open cutaneous ulcers that could predispose the subject to infection.
4.Severe heart failure (New York Heart Association [NYHA] class IV) or severe, uncontrolled cardiac disease.
5.Subjects with active tuberculosis. A tuberculosis test, interpreted by the investigator according to local standards or country-specific-guidelines, must be performed during the screening visit for subjects with no documentation of tuberculosis test results available within 4 weeks before the baseline visit.
6.Subjects with other rheumatic diseases, including but not limited to Lyme disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious arthritis, reactive arthritis, or overlap syndrome and secondary Sjögren's syndrome.
7.Cancer or history of cancer other than adequately treated cutaneous basal cell carcinoma or squamous cell carcinoma of the skin or in situ cervical cancer, with no evidence of recurrence.
8.History of alcohol or drug abuse that, in the opinion of the investigator, would interfere with the ability to comply with the study protocol.
9.Documented immunodeficiency disease, including but not limited to subjects with known human immunodeficiency virus (HIV) at the time of screening.
10.Subjects positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HepCAb), history of drug-induced liver injury, documented liver cirrhosis, or documented fibrosis at any time before the screening visit.
11.Any significant laboratory abnormality at screening, including the following:
•Hemoglobin (Hb) <85 g/L
•White blood cells (WBC) <3.50 x 10e9/L
•Platelets <125 x 109/L or =1000 x 10e9/L
•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 x the upper limit of normal (ULN)
•Serum creatinine (SCr) >177 µmol/L
12.Clinically significant finding on chest x-ray. Chest x-ray must be obtained during the screening period, unless a radiograph was obtained within 24 weeks prior to the baseline visit.
13.Prior use of B-cell depleting agents (e.g., rituximab).
14.Receipt of abatacept and/or tocilizumab.
15.Receipt of live attenuated vaccine =8 weeks prior to the screening visit.
16.Known hypersensitivity to mouse immunoglobulin, mouse/human chimeric immunoglobulin, or other biopharmaceutical proteins.
17.Hypersensitivity to corticosteroids and/or acetaminophen/paracetamol and/or diphenhydramine (or equivalent).
18.Receipt of the following within 24 weeks before the baseline visit:
•Any investigational drug, including biologics
•Any cytotoxic or immunosuppressive agent, including cyclophosphamide or chlorambucil
•Intravenous immunoglobulin (IVIG)
•Prosorba column (extracorporeal immunoadsorption protein A column)
•Leflunomide
•Intra-articular (IA) hyaluronic acid injections
19.Receipt of the following within 12 weeks before the baseline visit:
•Any disease-modifying antirheumatic drug (DMARD; including biol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate clinical efficacy and safety of 4 SBI-087 SC dosing regimens versus placebo in seropositive subjects with active RA on a stable background of MTX;Secondary Objective: Additional safety evaluations, health outcomes assessments, multiple-dose pharmacokinetics, pharmacodynamics, and evaluation of the relationship between B-cell depletion and SBI-087 serum concentration;Primary end point(s): The primary efficacy endpoint is the ACR20 response at week 16 for the modified intent-to-treat (mITT) population.
- Secondary Outcome Measures
Name Time Method