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.

Phase 1

Conditions: Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Moderate to severe rheumatoid arthritis
MedDRA version: 17.0Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859

Registration Number: EUCTR2011-002067-20-IE

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) as determined by the central laboratory 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). However, when deemed clinically necessary, 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 of contraception; therefore, subjects engaging or intending to engage in sexual activity must agree to employ 1 of the aforementioned acceptable
methods of contraception.
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 has received treatment with cyclophosphamide,chlorambucil,Janus kinase,spleen tyrosine kinase or phosphodiesterase 4 inhibitors or investigational agents such as spleen tyrosine kinase.
2. Sbj was randomized 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 [Criterion 3-4-5-6: please refer to the protocol –not modified by this amendment]
7. Sbj must not have a diagnosis of any other inflammatoryarthritis (eg psoriatic arthritis, ankylosing spondylitis or systemic lupus erythematosus/lupus nephritis) or have a Steinbrocker IV functional capacity. Sbj with Sjogren's Syndrome, as assessed by the PI to belimited to mild or moderate sicca symptoms that are considered to be a manifestation of secondary Sjogren's Syndrome related to RA, may be enrolled. However, systemic manifestations attributable to primary Sjogren's Syndrome are still considered exclusionary
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 activenmalignancy or a history of cancer. Exceptions are subjects with: no morethan 2 basal cell carcinomas excised prior to study entry - cervicalncarcinoma 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 recent history or existing condition, 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 but not limited to inflammatory bowel disease.
[Criterion 14-15-16-17-18-19: please refer to the protocol - not modified by this amendment]
20. Sbj with a history or active systemic/respiratory infection due to fungal, parasitic, or mycotic pathogens including but not limited to histoplasmosis, coccidiosis, paracoccidiosis, pneumocystis, blastomyces, aspergillus and nontuberculus mycobacteria. Radiographic findings suggestive of infections such as apical fibrosis, pleural thickening, pulmonary nodules (including any pulmonary nodules of unspecified significance), fibrotic scars, calcified granulomas, upper lobe infiltrates, cavitations and pleural effusions, calcified lung nodules, calcified hilar lymph nodes, and pericardial calcification or any other finding that could be suggestive of inactive TB or active TB, are sufficient grounds for exclusion. Radiographs will be assessed by a radiologist whose review of the radiograph includes a deliberate assessment of the presence or absence of TB infection, granulomatous disease, etc. Any abnormal radiographic
findings should be discussed with the Sponsor and/or Medical Monitor prior to subject enrollment
21. Sbj with a history of chronic or recurrent infections such as: - more than 3 episodes requiring antibiotics or antivirals during the preceding 6 mon