Study designed to assess the short- and long-term efficacy of CZP compared with Adalimumab, both when used with methotrexate (MTX) in the treatment of subjects suffering from rheumatoid arthritis that are not responding adequately to MTX. Adalimumab is a recombinant human IgG1 monoclonal antibody specific for human TNF that has been approved for the treatment of moderate to severe active RA in the USA, the European Union, and a number of other countries worldwide.

Conditions: Moderate to severe rheumatoid arthritis
MedDRA version: 14.1Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2011-002067-20-GR

Lead Sponsor: CB Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 892

Inclusion Criteria

1. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the subject. 2. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule or medication intake according to the judgment of the Investigator. 3. Subject is =18 years of age at Screening. 4. Subject must have a diagnosis of RA at Screening, as defined by the 2010 EULAR/ACR classification criteria (Aletaha D et al, 2010). 5. Subject must have a positive rheumatoid factor (RF) and/or a positive anti cyclic citrullinated peptide antibody (anti-CCP) at Screening. 6. Subject must have moderate to severe RA disease at Screening and Baseline defined as: a) Screening (all criteria required): i. =4 swollen joints (of 28 prespecified joints). ii. DAS28(ESR) >3.2. iii. CRP concentration =10mg/L (or 1.0mg/dL) and/or ESR (Westergren) =28mm/hr. b) Baseline (both criteria required): i. =4 swollen joints (of 28 prespecified joints). ii. DAS28(ESR) >3.2. 7. Subject is considered by the Investigator to be responding inadequately to treatment with MTX. An inadequate response to MTX is based on the opinion of the Investigator and following a minimum 12-week course of MTX therapy prior to the Screening Visit. 8. Subject is using MTX 15 to 25mg/week orally or subcutaneously at Screening and has used the same MTX regimen (dose and route) for a minimum of 28 days prior to Baseline 9. If using oral corticosteroids at Baseline, the subject is using a stable dose of =10mg (unchanged for at least 28 days prior to Baseline). One dose adjustment of no more than ±2.5mg during the 28 days prior to Baseline is acceptable provided the total dose does not exceed 10mg. 10. The subject, if female, must be either postmenopausal for at least 1 year, surgically sterile, or practicing an acceptable method of contraception, such as: a. oral / parenteral / implantable hormonal contraceptives, intrauterine device, or barrier and spermicide. b. Subjects must agree to use adequate forms of contraception from Screening through at least 10 weeks (or longer if required by local regulations as reflected by local product labelling) after the final dose of IMP. c. Male subjects must agree to ensure they or their female partner(s) use adequate contraception from Screening through at least 10 weeks (or longer if required by local regulations as reflected by local product labelling) after the final dose of IMP. Note: Abstinence is not an acceptable method.11 Subject must have completed the Washout Periods for analgesics and nonbiologic DMARDs (except MTX) in accordance with Table 6.1 of the protocol.
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 446
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 446

Exclusion Criteria

1. Subject has previously participated in this study (except when rescreening criteria apply) or subject (sbj) has received treatment with any biologic DMARD or cyclophosphamide,chlorambucil,Janus kinase,spleen tyrosine kinase or phosphodiesterase 4 inhibitors 2. Sbj participated in another study of medication or a med. device within the previous 3 months or is currently participating in another study of a medication or med. device under investigation 3. If a female subject, is breastfeeding, pregnant or plans to become pregnant during the study or within 10 wks following final dose of IMP or thereafter according to local regulations as reflected by local product labelling. 4. Sbj has a known hypersensitivity to any components of CZP or ADA or a history of an adverse reaction to polyethylene glycol 5. Sbj has a contraindication to the use of CZP, ADA, or MTX. 6. Sbj must not have a secondary, inflammatory or noninflammatory type of musculoskeletal condition (eg gout osteoarthritis or fibromyalgia) that in the PI’s opinion is symptomatic enough to interfere with evaluation of the effect of the IMP on the sbj’s primary diagnosis of RA. 7. Sbj must not have a diagnosis of any other inflammatory arthritis (eg psoriatic arthritis or ankylosing spondylitis) or have a Steinbrocker IV functional capacity 8. Sbj must not have received any experimental biological or nonbiological therapy for immuno inflammatory indications 9. The subject may not use prohibited medications and may only use (if needed) medications within protocol defined limitations as outlined in IC 11 and Table 6.1 10. Sbj with active malignancy or a history of cancer. Exceptions are subjects with: fewer than 3 excised basal cell carcinomas - cervical carcinoma in situ successfully surgically treated more than 5 yrs prior to Screening 11. Sbj with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease 12. Sbj with a history of blood dyscrasias 13. Sbj with a current or recent history, as determined by the PI, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease or other significant immunological/inflammatory disease including systemic lupus erythematosus or inflammatory bowel syndrome 14. Sbj with class III or IV congestive heart failure as defined by the New York Heart Association 1964 classification criteria 15. Sbj with a history of, or suspected, demyelinating disease of the central nervous system (eg multiple sclerosis or optic neuritis) 16. Sbj with any other condition (ie clinically significant laboratory values) which, in the judgment of the PI, would make the subject unsuitable for inclusion in the study 17. Sbj with a value =2.0xULN for any of the following liver function tests: • AST (glutamic oxaloacetic transaminase) • ALT (glutamate pyruvate transaminase [GPT]) 18. Sbj with a history of substance abuse (ie, alcohol, prescription, or illegal drugs) in the 6 months prior to Screening or considered to have a substance dependency (American Psychiatric Association, 1994) 19. Sbj has any medical or psychiatric condition that, in the opinion of the PI, can jeopardize or compromise the sbj’s ability to participate in this study 20. Sbj with a history or active systemic/respiratory infection due to fungal, parasitic, or mycotic pathogens including but not limited to histoplasmosis, coccidiosis, parac