Clinical trial NCT00977106: TORPEDO Study: A Study on Rapid Effect of Tocilizumab in Patients With Rheumatoid Arthritis With an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARDs) or Anti-TNF
Official title: Comparative Double Blind Placebo Controlled Clinical Study on Tocilizumab Rapid Efficacy on Patients Relief in rheumatoïd Arthritis With an Inadequate Response to DMARDs or Anti TNF :TORPEDO
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-09-15
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess the onset and maintenance of effect of tocilizumab on relief in patients with active moderate or severe rheumatoid arthritis who have had an inadequate response to DMARDs or anti-TNF. For the first, double-blind, part of the study patients will be randomized to receive an iv infusion of either 8mg/kg tocilizumab or placebo. After 4 weeks this will be followed by 11 months treatment with tocilizumab 8mg/kg iv infusion every 4 weeks. Methotrexate or DMARD therapy will be continued throughout study treatment. Target sample size is \>100.


Eligibility criteria: Inclusion Criteria:

* adult patients \>/= 18 years of age
* active moderate or severe rheumatoid arthritis of \<10 years duration with inadequate response to methotrexate or anti-TNF
* on methotrexate treatment for at least 10 weeks, at least 8 weeks on stable dose
* patients receiving oral corticosteroids and/or NSAIDs should be at stable dose for 4 weeks

Exclusion Criteria:

* rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA
* functional class IV by ACR classification
* history of inflammatory joint disease other than RA
* previous treatment with cell-depleting therapies, abatacept or rituximab
* active current or history of recurrent infection, or any major episode of infection requiring hospitalization or treatment with iv antibiotics \<4 weeks or oral antibiotics \<2 weeks prior to screening

Primary outcomes:
measure: Percentage of Participants With Clinically Significant Improvement in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 4
timeFrame: Week 4
Secondary outcomes:
measure: Patient Global Assessment of Disease Activity During the Double-Blind Treatment Period
timeFrame: Baseline, Weeks 1 and 4
measure: Patient Global Assessment of Disease Activity During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36 and 48
measure: Physician Global Assessment of Disease Activity During the Double-Blind Treatment Period
timeFrame: Baseline and Week 4
measure: Physician Global Assessment of Disease Activity During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Patient Global Assessment of Pain During the Double-Blind Treatment Period
timeFrame: Baseline and Week 4
measure: Patient Global Assessment of Pain During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: Synovitis Score During the Double-Blind Treatment Period Assessed Using B-Mode Ultrasound
timeFrame: Baseline, Weeks 1 and 4
measure: Synovitis Score During the Double-Blind Treatment Period Assessed Using Power Doppler Ultrasound
timeFrame: Baseline, Weeks 1 and 4
measure: Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using B-Mode Ultrasound
timeFrame: Weeks 12, 24, and 48
measure: Percent Change From Baseline in Synovitis Score During the Open Treatment Period Assessed Using Power Doppler Ultrasound
timeFrame: Weeks 12, 24, and 48
measure: Erythrocyte Sedimentation Rate During the Double-Blind Treatment Period
timeFrame: Baseline, Weeks 1 and 4
measure: Percent Change From Baseline in Erythrocyte Sedimentation Rate During the Double-Blind Treatment
timeFrame: Weeks 1 and 4
measure: Erythrocyte Sedimentation Rate During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: C-Reactive Protein During the Double-Blind Treatment Period
timeFrame: Baseline, Weeks 1 and 4
measure: Percent Change From Baseline in C-Reactive Protein During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: C- Reactive Protein During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Serum Amyloid A Component During the Double-Blind Treatment Period
timeFrame: Baseline, Weeks 1 and 4
measure: Percent Change From Baseline in Serum Amyloid A Component During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: Serum Amyloid A Component During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Beta 2 Microglobulin Levels During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Beta 2 Microglobulin Levels During the Double-Blind Treatment Period
timeFrame: Baseline, Weeks 1 and 4
measure: Percent Change From Baseline in Beta 2 Microglobulin Levels During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: Bone Mineral Density
timeFrame: Baseline and Week 48
measure: Percentage of Participants Treated With Corticosteroids Over the 1-Year Tocilizumab Period
timeFrame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: S-Sclerostin and P-Dkk1 (Wnt Signaling Inhibitor Dickkopf) Over the 1-Year Tocilizumab Period
timeFrame: Baseline, Weeks 12, 24, and 48
measure: Serum Procollagen Type II N-Propeptide (s-PIINP), Serum Procollagen Type I N Propeptide (s-PINP), and Serum Carboxy-Terminal Collagen Crosslinks-1 (s-CTX-I) Over the 1-Year Tocilizumab Period
timeFrame: Baseline and Weeks 12, 24, and 48
measure: Serum Osteogenic Growth Peptide (s-OGP) Over the 1-Year Tocilizumab Period
timeFrame: Baseline and Weeks 12 and 48
measure: Weekly Methotrexate (MTX) Dose
timeFrame: Baseline and Weeks 24 and 48
measure: HAQ-DI During the Double-Blind Treatment Period
timeFrame: Screening and Week 4
measure: HAQ-DI During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: Functional Assessment of Chronic Illness in Therapy - Fatigue (FACIT-F) During the Double-Blind Treatment Period
timeFrame: Day 0, Week 1, and Week 4
measure: Percent Change From Baseline in FACIT-F During the Double-Blind Treatment Period
timeFrame: Week 1 and Week 4
measure: FACIT-F During the Open Treatment Period
timeFrame: Baseline, Weeks 12, 24, 36, and 48
measure: Hemoglobin Concentration During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: Hemoglobin Concentration During the Open Treatment Period
timeFrame: Baseline, Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
measure: Tender Joint Count (TJC) Based on 28-Joint Count During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: Percent Change From Baseline in TJC Based on 28-Joint Count During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: TJC Based on 28-Joint Count During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: TJC Based on 40-Joint Count During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: Percent Change From Baseline in TJC Based on 40-Joint Count During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: TJC Based on 40-Joint Count During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: Swollen Joint Count (SJC) Based on 28-Joint Count During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: Percent Change From Baseline in SJC Based on 28-Joint Count During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: Swollen Joint Count (SJC) Based on 28-Joint Count During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: SJC Based on 40-Joint Count During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: Percent Change From Baseline in SJC Based on 40-Joint Count During the Double-Blind Treatment Period
timeFrame: Weeks 1 and 4
measure: SJC Based on 40-Joint Count During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: Disease Activity Score Based on 28-Joints Count (DAS28) During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: DAS28 During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
measure: Disease Activity Score Based on 40-Joints Count (DAS40) During the Double-Blind Treatment Period
timeFrame: Baseline and Weeks 1 and 4
measure: DAS40 During the Open Treatment Period
timeFrame: Baseline and Weeks 12, 24, 36, and 48
Other outcomes:
Locations:
city: Amiens
country: France
city: Amiens
country: France
city: Bayonne
country: France
city: Bois Guillaume
country: France
city: Bordeaux
country: France
city: Brest
country: France
city: Cahors
country: France
city: Chambray Les Tours
country: France
city: Clermont-ferrand
country: France
city: Echirolles
country: France
city: La Roche Sur Yon
country: France
city: Limoges
country: France
city: Lyon
country: France
city: Metz
country: France
city: Nantes
country: France
city: Orleans
country: France
city: Paris
country: France
city: Paris
country: France
city: Paris
country: France
city: Rennes
country: France
city: St Priest En Jarez
country: France
city: Toulouse
country: France
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: