A randomized, open-label 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.

• Register: EUCTR
• Last refreshed on: 28 January 2013
• Main ID: EUCTR2010-023587-40-FI
• Date of registration: 24/02/2011
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A randomized, open-label 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.
• Scientific title: A randomized, open-label 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.
• Date of first enrolment: 15/04/2011
• Target sample size: 96
• 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: yes 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

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Adult patients, >/= 18 years of age
- Rheumatoid arthritis of >/= 6 months duration (according to ACR criteria)
- Inadequate response due to inefficacy of treatment (at least 3 months) with only one approved TNF-agent other than adalimumab. Depending on the TNF-inhibitor, last dose of TNF-inhibitor should have been 1 to 8 weeks before randomization to the study
- On methotrexate treatment for >/=12 weeks immediately prior to baseline, with stable dose (10-25 mg/week) for the last 8 weeks
- Disease Activity Score (DAS28) >3.2 at baseline
- Oral corticosteroids (/=6 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 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 6 months following randomization
- Rheumatic autoimmune disease other than rheumatoid arthritis
- Prior history of or current inflammatory joint disease other than rheumatoid arthritis
- Functional class IV (ACR criteria)
- History of severe allergic reaction to human, humanized or murine monoclonal antibodies
- Known active current or history of recurrent infection (including TB)
- Primary or secondary immunodeficiency (history of or currently active)
- Body weight >150 kg
- Previous treatment with any cell-depleting therapies
- Previous treatment with tocilizumab
- Intra-articular or parenteral corticosteroids within 6 weeks prior to baseline


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Adult Rheumatoid Arthritis (RA)
MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: RoActemra®
Product Code: Ro 487-7533/F01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Humira®
Product Code: RO 551-6922
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-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

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.

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).

Primary end point(s): Clinical remission defined as DAS28<2.6 at week 24.

As a result of early termination of the recruitment prior to the completion of planned enrollment, the power/precision for the tests originally planned will not be sufficient. Therefore, revisions are necessary and will be specified in the SAP and noted in the final clinical study report. Descriptive statistics and/or patient listings will be prepared.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Secondary end point(s): • Proportion of patients with ACR20, ACR50 and ACR70 responses.
• Change from baseline in DAS28.
• Proportion of patients classified as categorical DAS28 responders (EULAR moderate and good response).
• Proportion of patients who achieve low disease activity defined as DAS28<3.2.
• Change from baseline in hemoglobin.
• Change from baseline in FACIT-Fatigue scores.
• Change from baseline in ACR core set (includes SJC, TJC, Patient Pain VAS, Patient Global VAS, Physician Global VAS, HAQ-DI, and acute phase reactants [hsCRP or ESR]).
• Change from baseline of RAPID3 score.
• Change from baseline in SF-36 scores (8 domain scores and physical and mental component summary measures [PCS and MCS, respectively])

Secondary ID(s)

2010-023587-40-ES

MA25522

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.