Local Open-Label Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARDs

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-004126-16-FI
• Date of registration: 15/07/2008
• Prospective Registration: Yes
• Primary sponsor: Roche Oy
• Public title: Local Open-Label Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARDs
• Scientific title: Local Open-Label Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Active Rheumatoid Arthritis on Background Non-biologic DMARDs who have an Inadequate Response to Current Non-biologic DMARDs
• Date of first enrolment: 05/09/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004126-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Finland

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or non-pregnant, non-nursing female 2. = 18 years of age 3. Diagnosis of moderate to severe active RA: =6 swollen and =6 tender joints, CRP=28 (mg/l) and/or ESR=30 (mm/hr) 4. Receiving treatment on an outpatient basis 5. Patients on = 1 non-biologic DMARDs at a stable dose for a period = 8 weeks prior to treatment (day 1) 6. Patients with inadequate clinical response to a stable dose of non-biologic DMARD 7. If patients are receiving an oral corticosteroid, the dose must have been stable for at least 25 out of 28 days prior to treatment (day 1) 8. 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:
Disease 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, 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 wheel chair, permitting little or no self-care)

Drug-specific
4.Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational agent, whichever is longer) before screening, 5.Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20), 6.Previous treatment with abatacept, adalimumab, etanercept, infliximab or remicade, 7.Treatment with IV gamma globulin, plasmapheresis or Prosorba® column within 6 months before baseline, 8.Immunization with a live/attenuated vaccine within 4 weeks prior to baseline, 9.Previous treatment with TCZ (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case by case basis), 10.Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation

Laboratory analyses (at screening)
11.Serum creatinine > 142 µmol/L (1.6 mg/dL) in female patients and > 168 µmol/L (1.9 mg/dL) in male patients and no active renal disease, 12.ALT (SGPT) or AST (SGOT) > 1.5 ULN (If initial sample yields ALT [SGPT] or AST [SGOT] > 1.5 ULN, a second sample may be taken and tested during the screening period), 13.Platelet count < 100 x 109/L (100,000/mm3), 14.Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L), 15.WBC count < 3.0 x 109/L (3000/mm3), ANC < 0.5 x 109/L (500/mm3), 16.ALC < 0.5 x 109/L (500/mm3), 17.Positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody, 18.Total bilirubin > ULN (If initial sample yields bilirubin > ULN, a second sample may be taken and tested during the screening period), 19.Triglycerides > 10 mmol/L (> 900 mg/dL) at screening (non-fasted)

General medical
20.Pregnant women or nursing (breastfeeding) mothers, 21.Females of child-bearing potential who are not using a reliable means of contraception, e.g. physical barrier (patient and partner), contraceptive pill or patch, spermicide and barrier, or IUD, 22.History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies, 23.CXR evidence of any clinically significant abnormality, 24.Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or GI disease, 25.In patients with a history of diverticulitis or diverticulosis requiring antibiotic treatment, the treating physician needs to consider the benefit-risk ratio, 26.A history of chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, diverticulitis or other symptomatic lower GI conditions that might predispose to perforations, 27.Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids, 28.Current liver disease as determined by principal investigator. Patients with prior history of ALT (SGPT) elevation are not excluded, 29.Known active current or history of recurrent bacterial

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: tocilizumab
Product Code: RO4877533 (TCZ)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
Current Sponsor code: RO 4877533
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: -20

Primary Outcome(s)

Main Objective: To assess the safety of tocilizumab (TCZ) monotherapy or in combination with non-biologic DMARDs in in patients with moderate to severe active RA.

Secondary Objective: To assess the efficacy of TCZ monotherapy or in combination with non-biologic DMARDs in patients with moderate to severe active RA.

Primary end point(s): Incidence of adverse events and serious adverse events during 24 weeks of TCZ monotherapy or combined treatment with TCZ and one or more of the background non-biologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in patients with moderate to severe active RA

Secondary ID(s)

ML22012