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| Name | Class |
|---|---|
| UCB Pharma | INDUSTRY |
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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.
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.
STUDY HYPOTHESIS
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| intensive, adapted treatment strategy | Experimental | Experimental: intensive, adapted treatment strategy Certolizumab pegol (CZP, Cimzia (R)): 200mg every 2 weeks after loading d 400mg at Weeks 0, 2 and 4 DMARD: 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 Glucocorticoids: At Week, 0 patients will be initiated on Spiricort (R) 20mg/d and tapered every 5 days Joint injections: 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 |
|
| fixed-dosed program | Active Comparator | Intervention: 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. DMARD: 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) Glucocorticoids: Prednisolone (Spiricort (R)) daily dose of ≤ 10 mg Joint injections: None |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Certolizumab Pegol | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| To assess the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 assessments | Efficacy rates as measured by the percentage of study participants achieving American College of Rheumatology 50% (ACR50) clinical response by the Week 24 | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| To compare the efficacy rates of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment | 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. | 8, 12, 18 and 24 weeks |
| 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 |
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Inclusion Criteria:
Male or female subjects aged 18 years or older at the time of consent
Able to give informed consent
Patients diagnosed as having established and active rheumatoid arthritis classified according to the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria (Aletaha D et al 2010) for a period of ≥ 3 months counting from the first DMARD treatment initiated. Active rheumatoid arthritis is characterised as all of the following:
Has a been found to be intolerant to, or had an inadequate clinical response to at least 1 DMARD
Is currently being treated with DMARDs for ≥ 12 weeks and has reached a stable dose for ≥ 4 weeks.
Is currently receiving a corticosteroid (e.g. prednisolone or equivalent) and has reached a stable dose of ≤ 10mg/d for ≥ 4 weeks (patients without current corticosteroid treatment for ≥ 4 weeks may also be included.
Available for the whole duration of the study.
Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for the duration of the study (starting from randomisation and ending up to Week 24 at Day 168/Safety follow-up visit). Must have a negative pregnancy test upon entry into the study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrolment, for the duration of the study (starting from randomisation and ending up to Week 24 at Day 168/Safety follow-up visit).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rueediger B Mueller, MD | Cantonal Hospital of St. Gallen | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kantonsspital St. Gallen | Sankt Gallen | Canton of St. Gallen | 9007 | Switzerland |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000068582 | Certolizumab Pegol |
| D013411 | Sulfadiazine |
| D008012 | Lidocaine |
| ID | Term |
|---|---|
| D011092 | Polyethylene Glycols |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D007140 | Immunoglobulin Fab Fragments |
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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* |
| weeks 8, 12, 18 and 24 |
| To compare the relative time taken for patients to reach remission across the two treatment groups | 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 | weeks 8, 12, 18 and 24 |
| To compare the cumulative corticosteroid dose for patients across the two study treatment groups following 24 weeks of treatment | 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 | 24 weeks |
| To compare the safety and tolerability of CZP between the two treatment groups following 8, 12, 18 and 24 weeks of treatment | 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 | 8, 12, 18 and 24 weeks |
| To conduct pharmacokinetic analysis to compare the CZP serum levels following 24 weeks of treatment across both of the treatment groups | 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) | 24 weeks |
| To compare the development of anti-CZP antibodies following 24 weeks of treatment across both of the treatment groups | 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) | 24 weeks |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007128 |
| Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D000083 | Acetanilides |
| D000813 | Anilides |