Rheumatoid arthritis MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
UCB Pharma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent is signed and dated by the subject or by the parent(s) or legal representative. 2. Subject/legal representative is considered reliable and capable of adhering to the protocol, visit schedule or medication intake according to the judgment of the Investigator. 3. Subjects must be at least 18 years old at the Screening Visit. 4. Female subjects must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device, or barrier and spermicide). Abstinence only is not an acceptable method. Subjects must agree to use adequate contraception during the study and for 10 weeks after their last dose of CZP (or longer if required by local regulations). 5. Subjects must have a diagnosis of adult-onset RA of at least 3 months duration but not longer than 15 years as defined by the 1987 American College of Rheumatology classification criteria. 6. Subjects must be rheumatoid factor positive and/or anti-CCP positive. 7. Inclusion Criterion 7 was deleted in Protocol Amendment 2 8. Subjects must have active RA disease as defined in the protocol. 9. Subjects must be on DMARD therapy for at least 12 weeks and the dose and route of administration should be stable for at least 8 weeks prior to Baseline. The eligibility for TNF therapy will be based upon appropriate medical judgment and as defined in local regulations and guidance and accoring to medical practice. 10. Subjects must be able and willing to comply with the requirements of the study protocol. 11. Subjects must have a normal renal function with creatinine within normal limits at screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subject has previously participated in this study or subject has previously been assigned to treatment in a study of the medication under investigation in this study. 2. Subject has a history of chronic alcohol or drug abuse within the last insert timeframe (eg, 6 months). 3. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject’s ability to participate in this study. 4. Subject has a known hypersensitivity to any components of the IMP as stated in this protocol. 5. Subjects must not have a secondary, noninflammatory type of musculoskeletal condition that in the Investigator’s opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the subject’s primary diagnosis of RA. 6. Subjects must not have a diagnosis of any other inflammatory arthritis. 7. Subjects must not have a history of an infected joint prosthesis at any time with that prosthesis still in situ. 8. Subjects must not have received any of the prohibited medication as detailed in the protocol. 9. Subjects must not have received any experimental nonbiological therapy in the 3 months or within 5 half-lives prior to Baseline (whichever is longer). 10. Subjects must not have received any experimental biological agent in the past 3 months or within 5 half-lives prior to Baseline (whichever is longer). 11. Subjects must not have received infliximab or abatacept therapy in the 3 months prior to Baseline. 12. Subjects must not have received adalimumab, golimumab or etanercept therapy in the 2 months prior to Baseline. 13. Subjects must not have received treatment with rituximab and tocilizumab. 14. Subjects must not have received more than 1 biological agent. 15. Subjects must not have been primary failures (ie, never achieved meaningful improvement) to prior anti-TNF therapy. 16. Subjects must not have contraindications for MRI and contrast agent. 17. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the trial or within 12 weeks following last dose of study drug. 18. Subjects with a history of chronic infection (more than 4 episodes requiring antibiotics/antivirals during the preceding year), recent serious or life–threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection. 19. Known TB disease, high risk of acquiring TB infection, or latent TB infection (as defined in the protocol). 20. Subjects at a high risk of infection. 21. Subjects with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease. 22. Subjects with concurrent acute or chronic viral hepatitis B or C. 23. Subjects with known human immunodeficiency virus (HIV) infection. 24. Subjects receiving live or attenuated vaccination within 8 weeks prior to Baseline. 25. Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than 5 years prior to Screening). 26. Subjects with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease. 27. Subjects with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria. 28. Subjects with a history of, or s
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To identify the first time point the OMERACT RAMRIS score for the activity of synovitis is statistically significantly reduced compared to Baseline in response to CZP therapy.;Secondary Objective: 1 To identify the efficacy of CZP on synovitis in dynamic MRI parameters of initial rate of enhancement (IRE), maximum enhancement (ME), and number of voxels (Nvox) with Plateau and Washout pattern 2 Correlation of reduction of synovitis as measured by MRI at Week 16 with: EULAR response ACR20, ACR50, and ACR70 response DAS28 response X-ray changes in bone mineral density 3 Change from Baseline for the OMERACT RAMRIS synovitis scores at Week 1 and Week 2 will be analyzed and compared between treatment groups (CZP versus PBO). 4 Assessment of clinical response during double-blind and OLE periods ;Primary end point(s): Primary efficacy variable: Change from Baseline (Day 0) in OMERACT RAMRIS synovitis score measured with MRI (gadolinium-containing contrast agent) of one hand and wrist at Weeks 1, 2, 4, 8, and 16. Safety variables: - Adverse events and serious adverse events - Physical examination (including signs and symptoms of latent or active tuberculosis) and vital signs - Clinical laboratory values (hematology, serum biochemistry, and urinalysis);Timepoint(s) of evaluation of this end point: 16 week double-blind, placebo controlled (during initial 2 weeks) randomized period, followed by a 24 week open-label extension. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Dynamic MRI parameters of IRE, ME, and Nvox at Day 0 and Weeks 1, 2, 4, 8, and 16 during the double-blind period. • EULAR response at Weeks 2, 4, 6, 8, 10, 12, 14, and 16 during the double-blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. • ACR20, ACR50, and ACR70 at Weeks 2, 4, 6, 8, 10, 12, 14, and 16 during the double blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. • Change from Baseline in DAS28-CRP at Weeks 2, 4, 6, 8, 10, 12, 14, and 16 during the double-blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. • DAS28-CRP remission status at Weeks 2, 4, 6, 8, 10, 12, 14, and 16 during the double blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. • Change from Baseline in bone mineral density (g/cm2) as measured by DXR at Week 16. • Change from Baseline in ACR components: tender joints and swollen joints, and Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16 during the double-blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. • Ratio to Baseline for C-reactive protein (CRP) at Weeks 2, 4, 6, 8, 10, 12, 14, and 16 during the double-blind period, then every 8 weeks during the OLE period, and at the Completion/Withdrawal Visit. ;Timepoint(s) of evaluation of this end point: 16 week double-blind, placebo controlled (during initial 2 weeks) randomized period, followed by a 24 week open-label extension. | — |
Countries
Denmark, Netherlands, Sweden
Contacts
Public ContactCT Registries & Results Disclosure
UCB Pharma
Outcome results
None listed