Protocol Title : A Randomised, open labelled study in anti ... - EME

More documents

Recommendations

Info

! STUDY SUMMARY/SYNOPSIS TITLE Developing a novel, biopsy-based diagnostic for patient stratification: “A Randomised, open labelled studyin anti- TNFa inadequate responders to investigate the mechanisms for Response - Resistance to Rituximab versus Tocilizumab in RA (R4-RA)”. SHORT TITLE R4-RA Protocol Version Number and Date Protocol 1, 18/08/2012 Methodology Type of study: single-blind, randomised controlled clinical trial Study Duration 4 years Study Centre Barts and The Royal London NHS Trust Objectives This study will aim to develop a diagnostic tool (immunohistochemical analysis of synovial tissue) for patient stratification into responsive/non-responsive categories with respect to Rituximab therapy in patients who have had an inadequate response to anti-TNF therapy. Specifically, can a diagnostic synovial biopsy showing a B-cell “rich/poor pathotype” define specific disease responsive/resistant subsets for patient stratification and help rationalize biologic drug choice? Phase of the Trial Phase IV study Number of Subjects/ 180 Patients Main Inclusion Criteria Patients will be recruited with active RA: 1. Patients who have failed anti-TNF therapy (inadequate responders – ir). 2. Patients who are seropositive for Rheumatoid Factor and/ or Anti-CCP antibodies. 3. Who are eligible for Rituximab therapy according NICE guidlines 4. Patients should be receiving a stable dose Methotrexate for at least 4 weeks prior to screening. 5. 2010 ACR / EULAR Rheumatoid Arthritis classification criteria for a diagnosis of Rheumatoid Arthritis. 6. Over 18 years of age 7. Patient must be capable of giving informed consent 8. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures Study: R4RA EudraCT: 2012-002535-28 6 / 34
Statistical Methodology and Analysis ! 1. For the randomized comparison of Rituximab versus Tocilizumab in B-cell poor patients, the primary endpoint will be analysed (by intent to treat) using the chisquared test for the difference between two proportions. Patients switching treatment before 6 months because of lack of response will be considered as nonresponders at 6 months. 2. For non-randomised comparisons between subgroups identified by B-cells in synovial biopsies, we will use the Fisher exact test comparing (i) response to Rituximab in B-cell poor patients compared to B-cell richThe definition of B-cell status will be clearly defined before the start of the trial. 3. A test of interaction between treatment and B-cell status (rich versus poor, excluding germinal centre) will be based on a likelihood ratio tests between nested logistic regression models. Study: R4RA EudraCT: 2012-002535-28 7 / 34
Page 1 and 2: Protocol Title : A Randomised, open
Page 3 and 4: Chief Investigator Agreement Page T
Page 5: Contact details: CPTU Contact: Beno
Page 9 and 10: Contents ! 1. INTRODUCTION 11 1.1.
Page 11 and 12: 1 INTRODUCTION ! 1.1 Background Rhe
Page 13 and 14: 1.3 Clinical Data 1.3.1 Rituximab C
Page 15 and 16: ! response is associated with absen
Page 17 and 18: ! 3 STUDY POPULATION 3.1 Number of
Page 19 and 20: ! • Slowly add the total volume o
Page 21 and 22: 4.4 IMP Stability Rituximab RIituxi
Page 23 and 24: ! A baseline synovial biopsy is man
Page 25 and 26: ! Small response - CDAI50 ≥ 50% i
Page 27 and 28: ! (the former usually precedes the
Page 29 and 30: ! 6.3 Investigators Assessment 6.3.
Page 31 and 32: ! 7.2 Secondary Endpoint Efficacy A
Page 33 and 34: ! completed screening procedures an
Page 35 and 36: 9 TRIAL COMMITTEES ! 9.1 Trial Mana
Page 37 and 38: Protocol Version 3 14/01/2013 Proto
Page 39 and 40: Protocol Version 3 14/01/2013 Chief
Page 41 and 42: Protocol Version 3 14/01/2013 Conta
Page 43 and 44: Protocol Version 3 14/01/2013 Stati
Page 45 and 46: Protocol Version 3 14/01/2013 Conte
Page 47 and 48: Protocol Version 3 14/01/2013 1 INT
Page 49 and 50: Protocol Version 3 14/01/2013 1.3 C
Page 51 and 52: Protocol Version 3 14/01/2013 medic
Page 53 and 54: Protocol Version 3 14/01/2013 3 STU
Page 55 and 56: Protocol Version 3 14/01/2013 Tocil
Page 57 and 58:
Protocol Version 3 14/01/2013 Log)
Page 59 and 60:
Protocol Version 3 14/01/2013 a - I
Page 61 and 62:
Protocol Version 3 14/01/2013 • F
Page 63 and 64:
Protocol Version 3 14/01/2013 • S
Page 65 and 66:
Protocol Version 3 14/01/2013 optim
Page 67 and 68:
Protocol Version 3 14/01/2013 days
Page 69 and 70:
Protocol Version 3 14/01/2013 negat
Page 71 and 72:
Protocol Version 3 14/01/2013 The s
Page 73 and 74:
Protocol Version 3 14/01/2013 (and
show all

Protocol Title : A Randomised, open labelled study in anti ... - EME

Create successful ePaper yourself

Delete template?

Save as template?