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.

• Register: EUCTR
• Last refreshed on: 1 February 2016
• Main ID: EUCTR2011-002067-20-ES
• Date of registration: 10/05/2012
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma SA
• Public title: 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.
• Scientific title: A multicenter, single blind, randomized parallel group study to assess the short and long term efficacy of certolizumab pegol plus methotrexate compared with adalimumab plus methotrexate in subjects with moderate to severe rheumatoid arthritis responding inadequately to methotrexate. - -
• Date of first enrolment: 26/06/2012
• Target sample size: 892
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002067-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Austria, Bulgaria, Canada, Czech Republic, Germany, Greece, Hungary, Ireland, Italy, Mexico, Portugal, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: CT Registries & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

• Name: CT Registries & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

Key inclusion & exclusion criteria

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 as defined by:
->=4 swollen joints (of 28 prespecified joints).
- DAS28(ESR) >3.2.
- CRP concentration >10mg/L (or 1.0mg/dL) and/or ESR (Westergren) >=28mm/hr.
7. Subject must have inadequately responded previously to MTX. Methotrexate-inadequate response is defined as not having achieved DAS28(ESR) =<3.2 during the 3 to 6 months prior to the Screening Visit according to the Investigator.
8. Subject is using MTX 15 to 25mg/week orally or subcutaneously at Baseline and has used the same MTX regimen (dose and route) during the 56 days prior to Baseline. A MTX dose at a minimum of 10mg/wk orally or subcutaneously is acceptable for subjects considered by the Investigator to be intolerant to a higher dose of MTX.
9. Subject, if using oral corticosteroids at Baseline, is receiving at a stable dose of <=10mg (unchanged for at least 28 days prior to Baseline).
10. The subject, if female, must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (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 from Screening through at least 10 weeks (or longer if required by local regulations) after the final dose of IMP. 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) after the final dose of IMP.
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 or subject has previously received any bDMARD during another clinical study or independent of another clinical study.
2. Subject has participated in another study of medication or a medical device within the previous 3 months or is currently participating in another study of a medication or medical device under investigation.
3. If a female subject, is breastfeeding, pregnant, or plans to become pregnant during the study or within 10 weeks following final dose of IMP or thereafter according to local regulations.
4. Subject has a known hypersensitivity to any components of CZP or ADA, or a history of an adverse reaction to polyethylene glycol (PEG).
5. Subject has a contraindication to the use of CZP, ADA, or MTX.
6. Subject must not have a secondary, noninflammatory type of musculoskeletal condition (eg, osteoarthritis or fibromyalgia) that in the Investigator?s opinion is symptomatic enough to interfere with evaluation of the effect of the IMP on the subject?s primary diagnosis of RA.
7. Subject must not have a diagnosis of any other inflammatory arthritis (eg, psoriatic arthritis or ankylosing spondylitis) or have a Steinbrocker IV functional capacity.
8. Subject must not have previously received any experimental nonbiological therapy.
9. Subject must be free of prohibited use or a limited use of concomitant medication as detailed in Table 6:1 of the Protocol.
10.Subject with concurrent malignancy or a history of malignancy (subjects with fewer than 3 excised basal cell carcinomas or with cervical carcinoma in situ successfully surgically treated more than 5 years prior to Screening may be included).
11. Subject with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.
12. Subjects with a history of blood dyscrasias.
13. Subject with a current or recent history, as determined by the Investigator, 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 irritable bowel syndrome.
14. Subject with class III or IV congestive heart failure as defined by the New York Heart Association 1964 classification criteria.
15. Subject with a history of, or suspected, demyelinating disease of the central nervous system (eg, multiple sclerosis or optic neuritis).
16. Subject with any other condition (ie, clinically significant laboratory values) which, in the judgment of the Investigator, would make the subject unsuitable for inclusion in the study.
17. Subject with a value >=1.2xULN for any of the following liver function tests (LFTs):
-Aspartate aminotransferase (AST) (glutamic oxaloacetic transaminase [GOT]).
-Alanine aminotransferase (ALT) (glutamate pyruvate transaminase [GPT]).
-Gamma-glutamyl transferase (GGT).
18. Subject has history of chronic alcohol or drug abuse within the previous 6 months.
19. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, can jeopardize or would compromise the subject?s ability to participate in this study.
20. Subject with history of or current clinically active infection (including chest x-ray) with Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, Mycobacteria (other than tuberculosis), Blastomyces, or Aspergillus.
21. Subject with a history

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Moderate to severe rheumatoid arthritis
MedDRA version: 14.1 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Cimzia
Product Name: Certolizumab pegol
Product Code: CDP870
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CERTOLIZUMAB PEGOL
CAS Number: 428863-50-7
Current Sponsor code: CDP870
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Trade Name: Humira
Product Name: Adalimumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Secondary Objective: -To investigate whether a Week 12 decision point is better at predicting the long term (Week 104) treatment success with CZP+MTX as compared with a Week 12 decision point with ADA+MTX
-To compare the % of subjects who meet ACR20 criteria at Week 6 between the CZP+MTX- and ADA+MTX randomized arms
-To compare the % of subjects with DAS28(ESR) LDA at Week 6 between the CZP+MTX- and ADA+MTX randomized arms
-To compare the % of subjects with DAS28(ESR) LDA at Week 12 between the CZP+MTX- and ADA+MTX randomized arms
-To evaluate the % of subjects reaching DAS28(ESR) LDA at Week 104 in subjects responding (in accordance with the Week 12 Responder definition) at both Week 6 and Week 12 when treated with CZP+MTX compared with ADA+MTX
-To evaluate the efficacy of CZP+MTX versus ADA+MTX in the physical function of Week 12 Responders at Week 104
-To evaluate the time to discontinuation in Week 12 Responders treated with CZP+MTX versus ADA+MTX

Primary end point(s): 1) Percentage of subjects meeting ACR20 criteria [American College of Rheumatology 20% criteria] in the CZP+MTX randomized group compared with the ADA+MTX randomized group;
2) Percentage of subjects with DAS28(ESR) LDA [Disease Activity Score-28 joint count(erythrocyte sedimentation rate) Low disease activity] in the CZP+MTX randomized group compared with the ADA+MTX randomized group (Group A versus Group C using all randomized subjects in the FAS)

Timepoint(s) of evaluation of this end point: 1) Week 12
2) Week 104

Main Objective: The primary objectives of this study in adult subjects with moderate to severe RA responding inadequately to MTX are as follows:
-To demonstrate the superiority of short term (Week 12) treatment in CZP+MTX randomized subjects as compared with ADA+MTX randomized subjects
-To demonstrate the superiority of long term (Week 104) treatment in CZP+MTX randomized subjects as compared with ADA+MTX randomized subjects, with subjects who switch treatment (Week 12 Non Responders) counted as treatment failures.

Secondary Outcome(s)

Secondary end point(s): Among the others:
1) The percentage of subjects with DAS28(ESR) LDA at Week 104 comparing the Week 12 Responder groups (Group A versus Group C).
2) The percentage of subjects with DAS28(ESR) LDA at Week 6 using all subjects, comparing the CZP+MTX randomized arm and the ADA+MTX randomized arm
3) The percentage of subjects with DAS28(ESR) LDA at Week 12 using all subjects, comparing randomized treatment groups CZP+MTX and ADA+MTX
4) The percentage of subjects with DAS28(ESR) LDA at Week 104 comparing the Week 12 Responder groups (Group A versus Group C), who also responded at Week 6 (ie, DAS28(ESR) <=3.2 or a DAS28(ESR) CFB reduction of >=1.2)

Timepoint(s) of evaluation of this end point: 1) Week 104
2) Week 6
3) Week 12
4) Week 104

Secondary ID(s)

2011-002067-20-DE

RA0077

Source(s) of Monetary Support

UCB Pharma SA