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Trial registered on ANZCTR


Registration number
ACTRN12608000397314
Ethics application status
Approved
Date submitted
27/05/2008
Date registered
5/08/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab versus Tocilizumab plus Non-biologic disease modifying antirheumatic drugs in Patients with Active Rheumatoid Arthritis
Scientific title
Multi-National Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab versus Tocilizumab plus Non-biologic disease modifying antirheumatic drugs in Patients with Active Rheumatoid Arthritis
Secondary ID [1] 573 0
MA21573, Issuing authority: Roche Products Pty Ltd
Universal Trial Number (UTN)
Trial acronym
Nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Active moderate to severe Rheumatoid Arthritis (RA) 3211 0
Condition category
Condition code
Inflammatory and Immune System 3376 3376 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tocilizumab 8mg/kg intra venously (IV), 60-minute infusion period, every 4 weeks for a total of 6 infusions
Intervention code [1] 2953 0
Treatment: Drugs
Comparator / control treatment
Background non-biologic disease modifying antirheumatic drugs (DMARDs).
The dosing of concomitant background non-biologic DMARD therapy will be the investigator's decision and these should be maintained at a stable dose throughout the study (from screening to Wk 24). Patients would remain on the DMARD therapy they were on, prior to study start. The group of patients who are on background DMARDs would also receive Tocilizumab 8mg/kg intra venously (IV), 60-minute infusion period, every 4 weeks for a total of 6 infusions. Some of the background DMARDs that patients might be using are: azathioprine, cyclosporine, penicillamine and hydroxychloroquine etc.
Control group
Active

Outcomes
Primary outcome [1] 4054 0
tolerability.Tests: laboratory assessments such as Haematology, blood chemistry & lipid panel. Patients will also be asked to complete quality of life questionnaires at every visit. Additionally, clinical assessments will be performed at every visit such as joint count.
Timepoint [1] 4054 0
These will be assessed at every study visit from screening, again at baseline (which is up to 28 days later), at Wk4, Wk8, Wk12, Wk16, Wk 20 and at Wk 24
Primary outcome [2] 4266 0
Safety will be assessed through standard adverse event (AE) reporting. Adverse events (AEs) of special interest: lipid evaluations, major adverse cardiac events, strokes, infections, neutrophil count and raised transaminases.
Timepoint [2] 4266 0
This will be measured at every visit (Wk4, Wk8, Wk12, Wk16, Wk 20 and at Wk 24)
Secondary outcome [1] 7213 0
Efficacy which will be measured as follows:
1. the number & percentage of patients achieving a clinically meaningful improvement in DAS28 (Disease activity score 28) (reduction of at least 1.2 units) at every visit and time to clinically meaningful improvement in DAS28 (Disease activity score 28)
2. number and percentage of patients achieving low disease activity (DAS28<3.2) (Disease activity score 28)
3. Number and percentage of patients achieving remission (DAS28<2.6) (Disease activity score 28)
4. Disease activity as measured by DAS28 (Disease activity score 28)
5.Number and percentage of patients achieving ACR (American College of Rheumatology)20, ACR(American College of Rheumatology)50, ACR(American College of Rheumatology)70 and ACR(American College of Rheumatology)90 response
6. Time to achievement of a clinically meaninful improvement in DAS 28 (Disease activity score 28) in time to ACR(American College of Rheumatology)20, ACR(American College of Rheumatology)50, ACR(American College of Rheumatology)70 and ACR(American College of Rheumatology)90 response
7. Mean change from baseline in individual parameters of ACR (American College of Rheumatology) core data set
8. CRP (C-reactive protein) & ESR (Erythrocyte sedimentation rate)
9.Improvement in physical functioning as measured using the HAQ (Health assessment questionnaire)
10.Improvement in SF-36 (Medical outcomes study short form health survey) score
11.Reduction in fatigue as measured using the Fatigue VAS (Visual analogue scale)
12.Change from baseline in individual parameters of ACR(American College of Rheumatology) core data set
13.Changes in physical function status at week 24 and over time as measured by the HAQ (health assessment questionnaire)
14.Proportion of patients achieving clinically meaningful HAQ (health assessment questionnaire) response, defined as an improvement of at least 0.22 units from baseline in the HAQ (health assessment questionnaire) disability index
15. Changes in patients' fatigue as assessed using the FACIT (Functional assessment of chronic illness therapy)-Fatigue score
Timepoint [1] 7213 0
Efficacy will be measured at every visit Wk4, Wk8, Wk12, Wk16, Wk 20 and at Wk 24

Eligibility
Key inclusion criteria
1.Male or non-pregnant, non-nursing female
2.>/-18 years of age
3.Diagnosis of moderate to severe active RA (DAS28>/-3.2) of >/- 6months duration
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 (Day1)
6. Patients with an inadequate clinical response to a stable dose of non-biologic DMARD or anti-TNF therapy
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 (Day1)
8.Able and willing to give written informed consent and comply with the requirements of the study protocol
Minimum age
18 Years
Maximum age
N/A
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1.Major surgery (incl joint surgery) within 8weeks prior to screening or planned major surgery within 6months following randomisation
2.Rheumatic autoimmune disease other than RA (rheumatoid arthritis), including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or significant systemic involvement secondary to RA(rheumatoid arthritis) (e.g.vasculitis, pulmonary fibrosis or Felty's syndrome)
Patient with interstitial pulmonary fibrosis and still able to tolerate MTX (methotrexate) therapy are permitted
Sjorgen's Syndrome with RA (rheumatoid arthritis) is permitted
3. Functional Clas IV as defined by the ACR (American College of Rheumatology) Classification of Functional Status in RA (rheumatoid arthritis) (largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care)
4.Prior history of or current inflammatory joint disease other than RA (rheumatoid arthritis) (e.g. gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropaty, Lyme disease)
5.Treatment with any investigational agent within 4weeks (or 5 half-lives of investigational agent, whichever is longer) before screening.
6.Previous treatment with any cell-depleting therapies, including investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20)
7.Previous treatment with abatacept
8.Treatment with IV gamma globulin, plasmapheresis or Prosorba column within 6months before baseline
9.Intraarticular or parenteral corticosteroids within 6weeks prior to baseline
10.Immunization with a live/attenuated vaccine within 4weeks prior to baseline
11.Previous treatment with TCZ (Tocilizumab) (an exception to this criterion may be granted for single-dose exposure upon application to the sponsor on a case by case basis)
12.Any previous treatment with alkylating agents, such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation
13.Serum creatinine >142

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 6104 0
2194
Recruitment postcode(s) [2] 6107 0
2217
Recruitment postcode(s) [3] 6106 0
2450
Recruitment postcode(s) [4] 6100 0
2600
Recruitment postcode(s) [5] 6099 0
3065
Recruitment postcode(s) [6] 6105 0
3168
Recruitment postcode(s) [7] 6102 0
3220
Recruitment postcode(s) [8] 6101 0
4870
Recruitment postcode(s) [9] 6103 0
5041
Recruitment outside Australia
Country [1] 863 0
Austria
State/province [1] 863 0
Country [2] 864 0
Canada
State/province [2] 864 0
Country [3] 865 0
Czech Republic
State/province [3] 865 0
Country [4] 866 0
Denmark
State/province [4] 866 0
Country [5] 867 0
Finland
State/province [5] 867 0
Country [6] 868 0
France
State/province [6] 868 0
Country [7] 869 0
Greece
State/province [7] 869 0
Country [8] 870 0
Hungary
State/province [8] 870 0
Country [9] 871 0
Ireland
State/province [9] 871 0
Country [10] 872 0
Italy
State/province [10] 872 0
Country [11] 873 0
Netherlands
State/province [11] 873 0
Country [12] 874 0
Norway
State/province [12] 874 0
Country [13] 875 0
Poland
State/province [13] 875 0
Country [14] 876 0
Portugal
State/province [14] 876 0
Country [15] 877 0
Romania
State/province [15] 877 0
Country [16] 878 0
Saudi Arabia
State/province [16] 878 0
Country [17] 879 0
Spain
State/province [17] 879 0
Country [18] 880 0
Sweden
State/province [18] 880 0
Country [19] 881 0
Switzerland
State/province [19] 881 0
Country [20] 882 0
Turkey
State/province [20] 882 0
Country [21] 883 0
United Kingdom
State/province [21] 883 0

Funding & Sponsors
Funding source category [1] 3431 0
Commercial sector/Industry
Name [1] 3431 0
Roche Products Pty Ltd
Address [1] 3431 0
4-10 Inman Road
Dee Why
NSW 2099
Country [1] 3431 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Roche Products Pty Ltd
Address
4-10 Inman Road
Dee Why
NSW 2099
Country
Australia
Secondary sponsor category [1] 3073 0
None
Name [1] 3073 0
Address [1] 3073 0
Country [1] 3073 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5456 0
Ethics committee address [1] 5456 0
Ethics committee country [1] 5456 0
Date submitted for ethics approval [1] 5456 0
21/05/2008
Approval date [1] 5456 0
Ethics approval number [1] 5456 0

Summary
Brief summary
This phase IIIb study will include adult patients, 18 years or older,body weight 150kg or less, with moderate to severe active rheumatoid arthritis (RA) of duration 6 months or more, who are inadequate responders to DMARDs or anti-TNF therapies. The primary objective is to assess the safety and tolerability of tocilizumab (TCZ) monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs). The secondary objectives is to assess the efficacy of TCZ monotherapy or in combination with non-biologic DMARDs. The study is designed so that patients would be on the study for 24 weeks, receiving 6 x 60min infusions of TCZ every 4 weeks. AEs and other safety variables will be analyzed using descriptive statistics. Safety and study data will be collected on an electronic CRF.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28508 0
Address 28508 0
Country 28508 0
Phone 28508 0
Fax 28508 0
Email 28508 0
Contact person for public queries
Name 11665 0
Christelle van Niekerk
Address 11665 0
Roche Pty Ltd
4-10 Inman Road
Dee Why
NSW 2099
Country 11665 0
Australia
Phone 11665 0
+61 2 9454 9368
Fax 11665 0
+61 2 9982 5269
Email 11665 0
christelle.van_niekerk@roche.com
Contact person for scientific queries
Name 2593 0
Christelle van Niekerk
Address 2593 0
4-10 Inman Road
Dee Why
NSW 2099
Country 2593 0
Australia
Phone 2593 0
+61 2 9454 9368
Fax 2593 0
+61 2 9982 5269
Email 2593 0
christelle.van_niekerk@roche.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary