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| [ Print-friendly version ] |
| Rituximab in patients with primary Sjögrens syndrome |
| ISRCTN | ISRCTN65360827 |
| ClinicalTrials.gov identifier | |
| Public title | Rituximab in patients with primary Sjögrens syndrome |
| Scientific title | A randomised double blind placebo controlled clinical trial of anti-B-cell therapy in patients with primary Sjögrens syndrome |
| Acronym | TRACTISS |
| Serial number at source | RR10/9389 |
| Study hypothesis | To assess the extent to which rituximab improves symptoms of fatigue and oral dryness in patients with primary Sjögrens syndrome. |
| Ethics approval | Leeds West Ethics Committee approval pending as of 30/06/2010. |
| Study design | Multicentre randomised double-blind placebo controlled phase III trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Primary Sjögrens syndrome (PSS) |
| Participants - inclusion criteria |
1. Aged between 18 and 80 years of age, either sex
2. A confirmed diagnosis of of primary Sjögrens syndrome by American–European Consensus Group (AECG) criteria with: 2.1. Positive labial gland biopsy** and/or 2.2. Positive for anti-Ro auto-antibodies greater than 1.5 upper limit of normal* 3. A stimulated salivary flow rate of greater than or equal to 0.5 ml in 5 minutes 4. An unstimulated salivary flow rate greater than 0 in 15 minutes 5. Be positive for anti-Ro auto-antibodies greater than 1.5 upper limit of normal 6. Symptomatic oral dryness (greater than or equal to 5/10 on patient-completed Likert***) 7. Symptomatic fatigue (greater than or equal to 5/10 on patient-completed Likert***) 8.1. At least one systemic feature of: 8.1.1. Hypergammaglobulinaemia (IgG over 16)*, or 8.1.2. Low complement C4*, or 8.1.3. Cryoglobulinaemia 8.2. Active/past history since diagnosis of the following (ascribed to Sjögrens syndrome): 8.2.1. Inflammatory polyarthritis 8.2.2. Purpura/cutaneous vasculitis 8.2.3. Lymphadenopathy 8.2.4. Persistent parotid salivary gland swelling not due to infection 8.2.5. Peripheral neuropathy (previously documented by nerve conduction tests) 8.2.6. Interstitial lung disease confirmed by high-resolution computed tomography (HRCT) 8.2.7. Renal tubular acidosis requiring treatment 8.2.8. Central nervous system (CNS) disease ascribed to Sjögrens syndrome (confirmed by magnetic resonance imaging [MRI]) 8.2.9. Myositis (creatine phosphokinase [CPK] greater than 2N and electromyogram [EMG] or biopsy evidence of myositis) 8.2.10. Patients with inflammatory arthritis 8.2.11. If greater than 10 years since diagnosis of primary Sjögrens syndrome, must have established systemic involvement 9. If on corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDS), hydroxychloroquine, methotrexate, or pilocarpine; have been on a stable dose for 4 weeks prior inclusion and expected to remain on this dose throughout the study 10. Given their written informed consent to participate in the trial and expected to be able to adhere to the study visit schedule and other protocol requirements * Anti-Ro/La antibody test, IgG, RF and C4 assays performed within 6 months of screening may be used to confirm eligibility. If greater than 6 months repeats should be performed locally at screening to confirm eligibility. ** A labial gland biopsy performed within 6 months of screening may be used to confirm eligibility. The labial gland biopsy SHOULD NOT be performed as part of the screening process. *** LIKERT range 0 - 10 with 10 corresponding to worst severity |
| Participants - exclusion criteria |
1. Diagnosis of secondary Sjögrens syndrome
2. Use of disease modifying anti-rheumatic drugs (DMARDs) or immunosuppressant therapies within 4 weeks prior to the first dose administration (glucocorticoids, salicylates, NSAIDs, analgesics are acceptable) 3. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment and for 12 months after treatment has finished 4. Men whose partners are of child-bearing potential but who are not willing to use appropriate medically approved contraception whilst receiving treatment and for 12 months after treatment has finished, unless they are surgically sterile 5. Use of other DMARDs or immunosuppressant therapies within 4 weeks prior to the first dose administration 6. Patients who are known to have serum hepatitis or are known carriers of the hepatitis B surface antigen (HBsAg), hepatitis C antibody, or have a known human immunodeficiency virus (HIV) positivity or a known history of tuberculosis 7. Any history of other autoimmune diseases or other form of immunodeficiency or neutropaenia less than 1.5 x 10^9/L 8. Any AECG exclusion criteria not covered elsewhere (graft versus host disease, primary lymphoma excluding PSS, sarcoidosis) 9. Any cancer that would normally preclude the use of rituximab within the past 5 years 10. Participation in a clinical study involving administration of an investigational drug within the past 4 weeks prior to the first infusion 11. A history of major surgery within 3 months prior to first infusion or have planned surgery during the study 12. Receipt of live/attenuated vaccine within 4 weeks prior to the first infusion 13. Previous exposure to rituximab or any other monoclonal antibody within the past 5 years 14. History of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection 15. History of moderate to severe congestive heart failure or other uncontrolled heart disease, or who have a clinically significant abnormal electrocardiogram (ECG) at the time of screening 16. History of receiving human/murine recombinant products or known allergy to murine products or any component of the active substance or any of its excipients or murine components 17. Presence of fibromyalgia, or diagnosed significant depression or anxiety 18. Current or a history of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis) 19. Any history of organ transplant (with the exception of a corneal transplant greater than 3 months prior to screening) 20. Presence of a clinically significant illness within 4 weeks of the start of the trial |
| Anticipated start date | 01/01/2011 |
| Anticipated end date | 01/07/2013 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet |
| Target number of participants | 110 patients |
| Interventions | Patients will receive two doses of rituximab (1000 mg) or placebo by intravenous (IV) infusion given with IV methylprednisolone (100 mg) at 2 week intervals at T = 0 and T = 2 weeks. This will be repeated at T = 24 weeks and T = 26 weeks. |
| Primary outcome measure(s) | A 30% reduction at 48 weeks from baseline in either oral dryness or fatigue measured using visual analogue scales (VAS; range 0 - 100 mm) |
| Secondary outcome measure(s) |
1. Fatigue (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48
2. Oral dryness (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 3. Ocular dryness (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 4. Patient global assessments (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 5. Physician global assessments (VAS Score; range 0 - 100 mm), evaluated at baseline and weeks 16, 24, 36 and 48 6. Salivary flow (stimulated and unstimulated salivary flow), performed at baseline, 16, 24, 36 and 48 weeks 7. Lachrymal flow (Schirmers I test of ocular function), performed at baseline, 16, 24, 36 and 48 weeks 8. Quality of life, evaluated at baseline and 16, 24, 36 and 48 weeks using the EULAR Sjögrens Syndrome Patient Reported Index (ESSPRI) 9. Quality of life, disease damage and disease activity indices, evaluated at baseline, 24 and 48 weeks using the following: 9.1. Sjögrens Syndrome Disease Damage Index (SSDDI) 9.2. Social Security Disability Insurance (SSDI) 9.3. EULAR Sjögrens Syndrome Disease Activity Index (ESSDAI) 9.4. Sjögrens Syndrome Disease Activity Index (SSDAI) 9.5. Sjögrens Systemic Clinical Activity Index (SCAI) 9.6. 36-item Short Form Health Survey (SF-36) 9.7. Profile of Fatigue and Discomfort–Sicca Symptoms Inventory (PROFAD-SSI) 10. Serological and peripheral blood inflammatory features (haematology biochemistry, serology and immunology assays), taken at baseline, weeks 16, 24, 26, 36 and 48 11. Incremental cost-effectiveness ratio (EQ-5D, health economics) evaluated at baseline, weeks 24 and 48 |
| Sources of funding | Arthritis Research UK (UK) - formerly Arthritis Research Campaign (ARC) (ref: 18810) |
| Trial website | |
| Publications | |
| Contact name | Mr Darren Walker |
| Address |
Clinical Trials Research Unit
University of Leeds |
| City/town | Leeds |
| Zip/Postcode | LS2 9JT |
| Country | United Kingdom |
| Tel | +44 (0)113 343 7792 |
| Fax | +44 (0)113 343 1471 |
| d.a.walker@leeds.ac.uk | |
| Sponsor | University of Leeds (UK) |
| Address |
c/o Claire Skinner
Faculty of Medicine and Health Research Office Room 10.110, Level 10 Worsley Building |
| City/town | Leeds |
| Zip/Postcode | LS2 9LN |
| Country | United Kingdom |
| C.E.Skinner@leeds.ac.uk | |
| Sponsor website: | http://www.leeds.ac.uk |
| Date applied | 17/06/2010 |
| Last edited | 09/07/2010 |
| Date ISRCTN assigned | 09/07/2010 |
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| © 2010 ISRCTN unless otherwise stated. | |
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