Phase IIa, multicenter, randomised, double-blind, placebo controlled study of the efficacy and safety of RO0506997, an a4 integrin antagonist, in combination with methotrexate, versus methotrexate alone, in patients with mild/moderate active rheumatoid arthritis (RA) who have had a partial response to a stable dose of methotrexate.
- Conditions
- Rhematoid ArthritisClassification code 10039073
- Registration Number
- EUCTR2004-004022-27-ES
- Lead Sponsor
- F.Hoffmann - La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 160
1.Patients with RA diagnosed according to the revised 1987 American Rheumatism Association (ACR) criteria.
2.Having RA for a minimum of 6 months.
3.Receiving treatment on an outpatient basis.
4.Have failed no more than 5 DMARDs.
5.Have received oral methotrexate (not necessarily at constant dose) for at least 24 weeks, with a stable dose for at least 8 weeks prior to their baseline visit. The dose of methotrexate at the baseline visit must be at least 10 mg/week and no greater than 25 mg/week.
6.Swollen joint count (SJC) = 6 (66 joint count) at baseline.
7.Tender joint count (TJC) = 8 (68 joint count) at baseline.
8.At least 1 of the following 3 parameters at screening:
- CRP = 1.5 mg/dL as determined by sensitive CRP assay
- ESR = 28 mm/h
- Morning stiffness > 45 minutes
9.Age = 18 years.
10.Corticosteroids (= 10 mg/d prednisolone or equivalent) or NSAIDs are permitted if stable for at least 4 weeks prior to baseline. These must remain stable for the duration of the study.
11.Able and willing to receive a stable dose of greater than or equal to 5 mg/week folic acid or the equivalent, given as either a single dose or as divided daily doses.
12.Able and willing to give written informed consent and comply with the requirements of the study protocol.
13.Women who are not either surgically sterile (tubal ligation or removal or ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least 1 year) must commit to use a barrier form of contraception in addition to either an intrauterine device or hormonal contraception until at least 1 month after the end of treatment. (Abstinence or sterile partner acceptable).
14.Men who are not surgically sterile must commit to use a condom for contraception until 1 month after the end of treatment. (Abstinence or sterile partner acceptable).
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.Elevation of hepatic transaminases (AST or ALT) > 2x the upper limit of normal during previous treatment with methotrexate or leflunomide, or >1.5x the upper limit of normal at screening.
2.Baseline QTc > 450 msec.
3.Bone/joint surgery within 6 months prior to screening (including joint fusion).
4.Rheumatic autoimmune disease other than RA (Sjögren’s Syndrome with RA is allowable).
5.Felty’s syndrome.
6.ARA functional class IV disease.
7.Active or history of rheumatoid vasculitis.
8.Prior history of gout.
9.Prior history of systemic diseases associated with arthritis, such as inflammatory bowel disease or infectious diseases associated with arthritis, such as Lyme disease or reactive arthritis.
10.Chronic fatigue syndrome or fibromyalgia.
11.Concomitant diseases or conditions that could interfere with clinical evaluations. This includes, but is not limited to, cancer, alcoholism, drug dependency or abuse, psychiatric diseases and active infections.
12.Any condition that would interfere with absorption of oral medicine.
Excluded Previous/concomitant medications
1.Concurrent treatment with any DMARD (DMARDS, including sulphasalazine (SSA) and hydroxychloroquine, must be washed out for 28 days prior to baseline).
2.Previous therapy with anti-TNF or IL-1 antagonist, or other biologic therapy at any time, including previous treatment with any cell depleting therapies (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD20).
3.Treatment with any investigational agent within 4 weeks or 5 half lives of screening, whichever the longer, or 3 months if the experimental agent is a DMARD
4.Patients receiving leflunomide within 6 months of screening, unless an eleven day standard cholestyramine washout is completed 28 days before screening.
5.Previous treatment within 6 months with immunosuppressive agents, for example azathioprine, mycophenolate mofetil, FK506 or cyclosporin A.
6.Previous treatment with alkylating agents within 6 months of the screening visit, such as cyclophosphamide or chlorambucil.
7.Greater than 10 mg/day of prednisolone (or equivalent) within 4 weeks prior to screening visit.
8.Intraarticular or parenteral corticosteroids within 4 weeks prior to the screening visit
9.Immunization with a live or attenuated vaccine (e.g. certain formulations of influenza vaccine) is specifically prohibited during the study, as well as patients, who have had recent (within 4 weeks) immunization with live or attenuated virus.
Exclusions for General Safety
1.Evidence of serious uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
2.Subjects susceptible to, or with a history of biliary obstruction or with either an autoimmune or a clinically significant concomitant disease that predisposes to such.
3.Uncontrolled disease states, such as, but not limited to asthma, where flares are commonly treated with oral or parenteral corticosteroids.
4.Active infection, with the exception of fungal infections of nail beds.
5.History of recurrent significant infection or history of recurrent bacterial infections (e.g. Neisseria, Pneumococcal infections).
6.Lymphopenia, defined as total lymphocyte count < 1 x 103/µL for more than 3 months duration immediately (within 6 months) prior to screening.
7.Primary or secondary immunodeficiency (history of or currently active).
8.Prior history of cancer, including solid tumors and hematologic maligna
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method