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

Registration Number: EUCTR2011-002067-20-CZ

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, 1 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 inflammatory
arthritis (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 be
limited 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 active
malignancy or a history of cancer. Exceptions are subjects with: no more
than 2 basal cell carcinomas excised prior to study entry - 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 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