A randomized, double-blind, parallel-group study of the reduction of signs and symptoms during treatment with tocilizumab versus adalimumab, both in combination with MTX, in patients with moderate to severe active rheumatoid arthritis and an inadequate response to treatment with only one TNF inhibitor. - ND

• Register: EUCTR
• Last refreshed on: 1 April 2013
• Main ID: EUCTR2010-023587-40-IT
• Date of registration: 27/04/2011
• Prospective Registration: No
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomized, double-blind, parallel-group study of the reduction of signs and symptoms during treatment with tocilizumab versus adalimumab, both in combination with MTX, in patients with moderate to severe active rheumatoid arthritis and an inadequate response to treatment with only one TNF inhibitor. - ND
• Scientific title: A randomized, double-blind, parallel-group study of the reduction of signs and symptoms during treatment with tocilizumab versus adalimumab, both in combination with MTX, in patients with moderate to severe active rheumatoid arthritis and an inadequate response to treatment with only one TNF inhibitor. - ND
• Date of first enrolment: 10/03/2011
• Target sample size: 700
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023587-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Finland, Germany, Greece, Italy, Netherlands, Spain, Sweden

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able and willing to give written informed consent and comply with the requirements of the study protocol. 2. Rheumatoid arthritis of =6 months duration diagnosed according to the revised 1987 ACR (Appendix 2). 3. Receiving treatment on an outpatient basis. 4. Age =18 years. 5. Have experienced an inadequate response due to inefficacy of treatment with only one approved anti-TNF agent (etanercept, infliximab, golimumab or certolizumab) other than ADA and were treated according to the respective Summary of Product Characteristic (SmPC) and the Prescribing Information (PI) for at least 3 months and not more than 15 months prior baseline. Patients should be randomized in the study without going through TNF inhibitor wash-out. The time between the last dose of TNF inhibitor and the randomization in the study should be between 1 and 8 weeks depending on the approved dosing interval as reported in the SmPC and PI. 6. Have received MTX for at least 12 weeks immediately prior to baseline, of which the last 8 weeks prior to baseline must have been at a stable dose of between 10 and 25 mg/week (by mouth [p.o.] or parenteral). 7. DAS28 score at baseline >3.2. 8. Oral corticosteroids (=10 mg/day prednisone or equivalent) and NSAIDs (up to the maximum recommended dose) are permitted if the dose has been stable for at least 6 weeks prior to baseline. 9. Females of child-bearing potential may participate in this trial only if using reliable means of contraception (e.g. physical barrier [patient and partner], contraceptive pill or patch, spermicide and barrier, or IUD). 10. Females of childbearing potential must have a negative serum pregnancy test at screening.
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 surgery within 6 months following randomization. 2. Rheumatic autoimmune disease other than RA. 3. Functional class IV as defined by the ACR Criteria for Classification of Functional Status in Rheumatoid Arthritis. 4. Prior history of or current inflammatory joint disease other than RA. 5. History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies including TCZ. Hypersensitivity to the active substance or to latex or to any of the excipients. 6. Evidence of serious uncontrolled concomitant cardiovascular (including moderate to severe heart failure [NYHA class III/IV]), nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease. 7. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids. Current liver disease as determined by investigator. (Patients with prior history of ALT elevation will not be excluded.) 8. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, clinically significant abnormalities on chest x-ray (CXR) as determined by the investigator, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with iv antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening. 9. Active TB requiring treatment within the previous 3 years. Patients previously treated for TB with no recurrence in the past 3 years are permitted. Patients who have a positive purified protein derivative (PPD) tuberculin skin test and have not been adequately treated for TB must be treated for latent TB with isoniazid (INH) for 1 month prior to enrollment whether or not they have been vaccinated in the past. Patients with a positive PPD that is =5mm at screening are not eligible for the study unless they begin treatment for latent TB with INH a minimum of 1 month prior to enrollment in the trial. The required total INH treatment duration is 9 months. Patients who had received BCG vaccination in the past should be screened using interferon-based testing (see section 5.3.2 for further details). Patients must have a negative CXR at enrollment. 10. Primary or secondary immunodeficiency (history of or currently active). 11. Evidence of active malignant disease, malignancies diagnosed or treated within the previous 10 years including hematologic malignancies and solid tumors (except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed or treated within the previous 20 years. 12. History of diverticulitis, diverticulosis or chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, GI bleeding or other symptomatic lower GI conditions that might predispose to perforations. 13. Pregnant women or nursing (breast-feeding) mothers. 14. History of alcohol, drug or chemical abuse within the 6 months prior to screening. 15. Neuropathies or other painful conditions that might interfere with pain evaluation. 16. Patients with lack of peripheral venous access. 17. Body

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 13.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: RoActemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: Ro 487-7533/F01
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Humira
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Adalimumab
CAS Number: 331731-18-1
Current Sponsor code: RO 551-6922
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To compare the effects of TCZ and ADA by assessing: • Efficacy parameters at week 24 by using American College of Rheumatology (ACR)criteria, European League Against Rheumatism (EULAR) criteria, low disease activity scores, patient-reported health assessments (Health Assessment Questionnaire[HAQ],Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire [FACIT-Fatigue Scale], Short Form-36 [SF-36], Routine Assessment of Patient Index Data [RAPID3]). • Change of haemoglobin levels at week 24 vs baseline. • Safety throughout the study.

Primary end point(s): The primary endpoint is the proportion of patients achieving clinical remission, defined as DAS28<2.6, at Week 24.

Main Objective: To assess the efficacy of treatment with tocilizumab (TCZ) 8 mg/kg intravenously (iv) (every 4 weeks) versus adalimumab (ADA) 40 mg subcutaneously (sc) (every 2 weeks), both in combination with methotrexate (MTX), with regard to achievement of clinical remission as measured by Disease Activity Score 28 (DAS28) <2.6 at the end of 24 weeks of treatment in patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate efficacy response to treatment with only one tumor necrosis factor (TNF) inhibitor (other than ADA).

Secondary ID(s)

2010-023587-40-ES

MA25522