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: 9 December 2013
• Main ID: EUCTR2011-002067-20-GR
• Date of registration: 13/12/2012
• 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: 10/01/2013
• 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, 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 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

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: 100000004859

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 percentage of subjects who meet ACR20 criteria at Week 6 between the CZP+MTX- and ADA+MTX randomized arms
• To compare the percentage of subjects with DAS28(ESR) LDA at Week 6 between the CZP+MTX- and ADA+MTX randomized arms
• To compare the percentage of subjects with DAS28(ESR) LDA at Week 12 between the CZP+MTX- and ADA+MTX randomized arms
• To evaluate the percentage 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

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.

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

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