Clinical trial NCT00845832: A Study of Combination Treatment With MabThera (Rituximab) and RoActemra (Tocilizumab) Versus RoActemra in Patients With Rheumatoid Arthritis With an Incomplete Response to Methotrexate
Official title: A Randomized, Active Controlled, Double-blind, Study to Compare the Safety and Reduction in Disease Activity With the Combination of Rituximab (MabThera®)and Tocilizumab (RoActemra®) Versus Tocilizumab in Patients With Active Rheumatoid Arthritis With an Incomplete Response to Methotrexate
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-02-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 part study will investigate the safety, tolerability and efficacy of MabT hera in combination with RoActemra in patients with active rheumatoid arthritis despite a stable dose of methotrexate. In Part 1 of the study, patients will be randomized to receive either MabThera 0.5g iv or placebo on days 1 and 15, follo wed by RoActemra at one of the ascending doses between 2mg/kg and 8mg/kg at week s 4, 8 and 12 (MabThera arm) or 8mg/kg (placebo arm). In Part 2, additional pati ents will be randomized to one of 2 groups to receive MabThera 0.5g on days 1 an d 15 followed by the selected dose (from Part 1)of RoActemra at weeks 4, 8 and 1 2, or placebo on days 1 and 15 followed by RoActemra 8mg/kg at weeks 4,8 and 12.

All patients will then be eligible to receive extension treatment withRoActemra every 4 weeks. The anticipated time on study treatment is 12 months, and the tar get sample size is \<100 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, 18-65 years of age;
* rheumatoid arthritis, functional status I-III;
* SJC\>=4 (28 joint count) and TJC\>=4 (28 joint count) at screening and baseline;
* RF and/or anti-CCP positive;
* may have failed up to 1 approved anti-TNF agent (infliximab, etanercept or adalimumab);
* inadequate response to methotrexate, at a dose of 7.5-25mg weekly for at least 12 weeks, at a stable dose for past 4 weeks.

Exclusion Criteria:

* rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis;
* history of, or current, inflammatory joint disease other than rheumatoid arthritis;
* diagnosis of juvenile idiopathic arthritis and/or rheumatoid arthritis before age 16;
* significant cardiac or pulmonary disease;
* previous treatment with any biologic agent for rheumatoid arthritis (other than infliximab, etanercept or adalimumab).

Primary outcomes:
measure: Percentage of Participants Achieving Low Disease Activity (LDA) at Week 16 Assessed Using Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Achieving Remission at Week 16 Assessed Using DAS28-ESR
timeFrame: Week 16
measure: Percentage of Participants by European League Against Rheumatism (EULAR) Response Category at Week 16
timeFrame: Week 16
measure: Change From Baseline in DAS28-ESR
timeFrame: Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
measure: Clinical Disease Activity Index Scores
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48
measure: Simplified Disease Activity Index (SDAI) Scores
timeFrame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48
measure: Change From Baseline to Week 48 in SJC and TJC
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Health Assessment Questionnaire (HAQ)
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in C-Reactive Protein (CRP)
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in ESR
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Physician's Global Assessment of Disease Activity
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Participant's Global Assessment of Disease Activity
timeFrame: Baseline and Week 48
measure: Change From Baseline to Week 48 in Participant's Assessment of Pain
timeFrame: Baseline and Week 48
Other outcomes:
Locations:
city: Le Kremlin Bicetre
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Strasbourg
country: France
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Heidelberg
country: Germany
city: Köln
country: Germany
city: Wuerzburg
country: Germany
city: Athens
country: Greece
city: Thessaloniki
country: Greece
city: Amsterdam
country: Netherlands
city: Leiden
country: Netherlands
city: Bytom
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Santander
country: Spain
state: Cantabria
city: Santiago de Compostela
country: Spain
state: La Coruña
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Bern
country: Switzerland
city: Lausanne
country: Switzerland
city: Newcastle Upon Tyne
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: