RICE: Remission by Intra-articular Injection Plus CErtolizumab (RICE)
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|ClinicalTrials.gov Identifier: NCT02293590|
Recruitment Status : Completed
First Posted : November 18, 2014
Last Update Posted : August 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: Certolizumab Pegol||Phase 2|
Certolizumab pegol (CZP) is a tumor necrosis factor (TNF) antagonist which is marketed for the treatment of moderate to severe rheumatoid arthritis (RA) (Keystone, 2008) when given in combination with methotrexate (MTX). CZP is a PEGylated Fab' fragment of humanized anti-TNF antibody with a high affinity for TNF.
RA is a chronic inflammatory autoimmune disease with multiple treatment strategies and combination therapies available including analgesia, anti-inflammatory drugs and disease-modifying anti-rheumatic drugs. Previous trials have demonstrated positive results from the use of CZP but have compared its use to placebo in a fixed dose concomitant medication regime rather than using a more realistic dynamic treatment strategy normally employed in the clinical outpatient care of RA.
This trial is aimed at comparing the use of CZP in patients with moderate to severe RA when administered in conjunction with an intensive, adapted treatment strategy (Group A) versus a fixed-dosed program (Group B). CZP will be given in conjunction with MTX (a disease modifying anti-arthritic drug - or DMARD), steroidal therapy in the form of prednisolone and joint infiltrations of triamcinolone (another corticosteroid) and lidocaine (a pain therapy). Both treatment arms will include these concomitant medications but there will be an intensive adaptive approach adopted for the 'treat to target' population of Group A with a more fixed-dose approach set-out for Group B. Patients will be centrally randomized after screening to ensure a 50:50 ratio for both Groups in the study.
Tight control of an adaptive concomitant treatment strategy after initiation of CZP will lead to an improved outcome of RA patients with an active disease despite DMARD treatment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Randomised Study to Compare the Efficacy of Certolizumab Pegol (CZP) Plus a Dynamic or Fixed Dose Treatment Strategy in Patients With Rheumatoid Arthritis, a Phase II Study|
|Actual Study Start Date :||November 2013|
|Actual Primary Completion Date :||December 22, 2017|
|Actual Study Completion Date :||January 15, 2018|
Experimental: intensive, adapted treatment strategy
Experimental: intensive, adapted treatment strategy Certolizumab pegol (CZP, Cimzia (R)): 200mg every 2 weeks after loading d 400mg at Weeks 0, 2 and 4
Patients without sufficient treatment response will be taken to the next step according to the therapeutic algorithm or next drug, for example: 15=>25mg Metoject (R)/week => Leflunomide Gebro (R)20mg/d => Salazopyrine EN(R) 2000mg/d
At Week, 0 patients will be initiated on Spiricort (R) 20mg/d and tapered every 5 days
Starting at Week 0 up to 5 joint injections may be conducted into synovitic joints at every visit of the study.
The maximum cumulative Lederlon (R) dose is 100mg/visit. Joints are to be infiltrated with the following doses of triamcinolone and lidocaine
Drug: Certolizumab Pegol
Active Comparator: fixed-dosed program
Certolizumab pegol (Cimzia (R), CZP) CZP of 400mg at Weeks 0, 2 and 4, followed by 200mg injections from Week 6, every 2 weeks until Week 24.
Patients are to continue to receive their stable weekly dose of DMARD as noted at study entry for the duration of the study (24 weeks)
Prednisolone (Spiricort (R)) daily dose of ≤ 10 mg
Drug: Certolizumab Pegol
- To assess the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 assessments [ Time Frame: 24 weeks ]Efficacy rates as measured by the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24
- To compare the efficacy rates of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment [ Time Frame: 8, 12, 18 and 24 weeks ]Efficacy rates as measured by ACR20/50/70 at weeks 8, 12, 18 and 24 weeks to determine the % of treatment responders in each study Group over the study period.
- To compare the proportion of patients reaching either a low disease activity status (LDAS) or a full remission of their RA across both treatment groups at weeks 8, 12, 18 and 24 [ Time Frame: weeks 8, 12, 18 and 24 ]
Efficacy rates as measured by patients achieving Low DAS is defined (LDAS) or a full clinical remission according to the EULAR at weeks 8, 12, 18 and 24 weeks. LDAS as a DAS-28 score of less than 3.2. The DAS-28 is defined by the number of tender and swollen joints calculated from 28 joints mainly from the upper limbs, the ESR and the patient's global assessment of disease activity.
Remission will be defined as a DAS-28 score of less than 2.6 and/or according to the Boolean definition of remission (Felson 2011): swollen joint count, tender joint count, patients' global assessment of disease activity, CRP (mg/dl) all ≤1*
- To compare the relative time taken for patients to reach remission across the two treatment groups [ Time Frame: weeks 8, 12, 18 and 24 ]Efficacy rates as measured by the average number of weeks of treatment required for patients to reach remission of their RA. Clinical remission to be evaluated via the EULAR and DAS-remission criteria
- To compare the cumulative corticosteroid dose for patients across the two study treatment groups following 24 weeks of treatment [ Time Frame: 24 weeks ]Efficacy as calculated of the cumulative corticosteroid dose for patients completing the 24 week study period across the two treatment groupsCalculation of the cumulative corticosteroid dose for patients completing the 24 week study period across the two treatment groups
- To compare the safety and tolerability of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment [ Time Frame: 8, 12, 18 and 24 weeks ]Safety as calculated by the occurrence of treatment emergent adverse event (TEAE, adverse events occurring after baseline of the study) across the two treatment groups
- To conduct pharmacokinetic analysis to compare the CZP serum levels following 24 weeks of treatment across both of the treatment groups [ Time Frame: 24 weeks ]Efficacy analysis as analysed by a pharmacokinetic assessments are to be conducted at Visit 3/week 4 (day 28) and visit 7/Week 24 (Day 168 post initiation of CZP treatment)
- To compare the development of anti-CZP antibodies following 24 weeks of treatment across both of the treatment groups [ Time Frame: 24 weeks ]Efficacy analysis as analysed two single timepoint anti-CZP antibody assessments are to be conducted at Visit 2/Week 0 and Visit 7/Week 24 (Day 168 post initiation of CZP treatment)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02293590
|Kantonsspital St. Gallen|
|St. Gallen, Saint Gallen, Switzerland, 9007|
|Study Chair:||Rueediger B Mueller, MD||Cantonal Hospital of St. Gallen|