Randomized placebo-controlled study to evaluate the safety and efficacy of adding tocilizumab (TCZ) to methotrexate (MTX) versus switching to TCZ (placebo-controlled), with possible addition of other disease-modifying anti-rheumatic drugs (DMARDs), in patients with active rheumatoid arthritis who have inadequately responded to prior MTX treatment. - ND

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2008-001847-20-IT
• Date of registration: 18/12/2008
• Prospective Registration: Yes
• Primary sponsor: ROCHE
• Public title: Randomized placebo-controlled study to evaluate the safety and efficacy of adding tocilizumab (TCZ) to methotrexate (MTX) versus switching to TCZ (placebo-controlled), with possible addition of other disease-modifying anti-rheumatic drugs (DMARDs), in patients with active rheumatoid arthritis who have inadequately responded to prior MTX treatment. - ND
• Scientific title: Randomized placebo-controlled study to evaluate the safety and efficacy of adding tocilizumab (TCZ) to methotrexate (MTX) versus switching to TCZ (placebo-controlled), with possible addition of other disease-modifying anti-rheumatic drugs (DMARDs), in patients with active rheumatoid arthritis who have inadequately responded to prior MTX treatment. - ND
• Date of first enrolment: 18/01/2009
• Target sample size: 470
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001847-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: tocilizumab in combinazione con metotrexate

Countries of recruitment

Denmark, Estonia, France, Germany, Greece, Italy, Latvia, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or non-pregnant, non-nursing female 2. > 18 years of age 3. Body weight < 150 kg 4. Patients currently experiencing active moderate to severe RA (DAS28 > 4.4) according to the revised 1987 ACR criteria for the diagnosis of RA 5. Radiographic evidence of at least one joint with definite erosion attributable to RA as determined by the central reading site. Any joint of the hands, feet or wrists can be considered with the exception of distal interphalangeal joints of the hands 6. Patients currently receiving MTX for at least 12 weeks and who have received MTX at a stable dose of at least 15 mg/week for at least 6 weeks prior to treatment (day 1), with the following exception: 10 mg instead of 15 mg is acceptable in patients with a body weight < 50 kg, low grade toxicity to MTX (such as nausea), or calculated glomerular filtration rate (or creatinine clearance) < 60 mL/min 7. If patients are receiving an oral corticosteroid, the dose must have been < 10 mg/day prednisone (or equivalent) and stable for at least 25 out of 28 days prior to treatment (day 1) 8. Patients receiving treatment on an outpatient basis 9. Patients able and willing to give written informed consent and comply with the requirements of the study protocol
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

Exclusion criteria:
1. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization 2. Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g. vasculitis, pulmonary fibrosis or Felty?s syndrome). Patients with interstitial pulmonary fibrosis and still able to tolerate MTX therapy are permitted. Sjögren?s Syndrome with RA is permitted 3. Functional class IV as defined by the ACR Classification of Functional Status in RA (largely or wholly incapacitated with patient bedridden or confined to wheelchair, permitting little or no self-care) 4. Prior history of or current inflammatory joint disease other than RA (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adult patients with active moderate to severe (DAS28 > 4.4) rheumatoid arthritis (RA) who have inadequately responded to prior conventional MTX treatment and have not been treated with any biologic agent before.
MedDRA version: 9.1 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid

Intervention(s)

Product Name: Tocilizumab
Product Code: RO04877533
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 375823-41-9
Current Sponsor code: RO04877533
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 80-

Trade Name: Methotrexate Lederle 2.5 mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Tocilizumab
Product Code: RO04877533
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 375823-41-9
Current Sponsor code: RO04877533
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-

Primary Outcome(s)

Secondary Objective: - To compare the effect of TCZ plus MTX versus TCZ plus PBO on progression of structural damage at week 52 in MTX inadequate responders with moderate to severe active RA who may receive a DMARD in addition to TCZ and MTX/PBO after week 24 - To compare the safety of TCZ plus MTX versus TCZ plus PBO with regard to adverse events (AEs) and laboratory assessments in MTX inadequate responders with moderate to severe active RA who may receive a DMARD in addition to TCZ and MTX/PBO after week 24 - To assess clinical and radiographic efficacy over 2 years (including earlier time points) of treatment with TCZ plus MTX versus TCZ plus PBO as assessed by measures including clinical disease activity, x-rays and quality of life and functional scales.

Main Objective: To compare the effect of TCZ in combination with MTX versus TCZ in combination with placebo (PBO; matching MTX) on DAS28 remission at week 24 in MTX inadequate responders with moderate to severe active RA

Primary end point(s): DAS28 remission rate (RR) at week 24

Secondary ID(s)

MA21488

2008-001847-20-ES