Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease

Rheumatoid Arthritis Clinical Trial

— CREDO 3  

Official title:

A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02760433
• Other study ID #: CL04041025
• Secondary ID: 2015-005308-27
• Status: Completed
• Phase: Phase 3
• Start date: January 25, 2017
• Est. completion date: October 1, 2019

Study information

• Verified date: September 2023
• Source: R-Pharm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine how effective and safe the study drug Olokizumab was in patients with Rheumatoid Arthritis (RA) who had been already receiving, but not fully responding to treatment with an existing medication called a tumour necrosis factor alpha inhibitor The primary objective of this study was to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by TNF-α inhibitor (TNFi) therapy.

Description:

The goal of this Phase III study was to assess the efficacy, safety and tolerability of OKZ in subjects with moderately to severely active RA who had responded inadequately to TNFi therapy. The primary endpoint of the trial was assessed at Week 12. Olokizumab was expected to reduce the disease activity and improve physical function. The study was expected to provide safety information in a large group of subjects over at least a 24 week period. This was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. This study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety FollowUp Period from Week 24 to Week 44. A total of 350 subjects were planned to be randomized.Subjects were assessed for eligibility to enter the study during a 4-week Screening Period. Eligible subjects were randomized at Visit 2 in a 2:2:1 ratio in one of 3 treatment groups (planned 140, 140, and 70 subjects per group, respectively) : 1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo OKZ q4w to maintain blinding) + MTX for 24 weeks, 2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX for 24 weeks or 3. Placebo: SC injection of placebo q2w + MTX for 16 weeks. Subjects who received placebo were re-randomized at Week 16 to receive 64 mg OKZ q4w + Methotrexate or 64 mg OKZ q2w +Methotrexate for 8 weeks. Throughout the double-blind Treatment Period, all subjects were required to remain on a stable dose of background MTX with a stable route of administration. Concomitant treatment with folic acid was required for all subjects. The last dose of OKZ was administered at Week 20 for subjects receiving OKZ 64 mg q4w and at Week 22 for subjects receiving OKZ 64 mg q2w. Following Visit 2 (randomization; Week 0), subjects returned to the study site at least every 2 weeks through Week 24 for response and safety assessments. At Week 14, subjects who did not improve by at least 20% in both swollen and tender joint counts were classified as nonresponders and were administered sulfasalazine and/or hydroxychloroquine as rescue medication in addition to the assigned treatment. After completion of the 24-week double-blind Treatment Period, subjects either rolled over into the long-term open-label extension (OLE) study or entered the Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for visits +4, +8, and +22 weeks after the last dose of study treatment. Subjects who discontinued randomized treatment prematurely were required to come for the End of Treatment (EoT) Visit 2 weeks after the last study treatment administration and then continue with the scheduled study visits. Adverse events (AEs) were assessed throughout the study (starting when the subject signed the informed consent form) and evaluated using the Common Terminology Criteria for Adverse Events Version 4.0. There was ongoing monitoring of safety events, including laboratory findings, by the Sponsor or the Sponsor's designee. In addition, safety was assessed throughout the study by an independent Data Safety Monitoring Board and potential major adverse cardiac events were evaluated by an independent Cardiovascular Adjudication Committee. The study was conducted at 123 sites across 11 countries globally (in US,EU, Russian Federation, Asia, Latin America)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 368
• Est. completion date: October 1, 2019
• Est. primary completion date: September 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Subjects may be enrolled in the study only if they meet all of the following criteria.

• Subjects willing and able to sign informed consent
• Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 24 weeks prior to Screening. (If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data.)
• Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or =10 mg/week if there is documented intolerance to higher doses)
• The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
• Subjects must be willing to take folic acid or equivalent throughout the study.
• Subjects must have moderately to severely active RA disease as defined by all of the

following:

• =6 tender joints (68 joint count) at Screening and baseline; and
• =6 swollen joints (66 joint count) at Screening and baseline; and
• C-reactive protein (CRP) above Upper limit of normal (ULN) at Screening based on the central laboratory results.
• Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with =1 licensed TNFi following at least 12 weeks of therapy with that agent.

Inadequate response to treatment is classified as either:

• Primary failure: The absence of any documented clinically significant response; or
• Secondary failure: Documented initial response with subsequent loss of that response or partial response

Exclusion Criteria:

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus) (However, subjects may have secondary Sjogren's syndrome or hypothyroidism.)
• Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
• Prior exposure to any licensed or investigational compound directly or indirectly targeting Interleukin (IL) 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase [SYK] inhibitors)
• Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19) with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA).
• Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of

RA):

1. 4 weeks for etanercept and anakinra

2. 8 weeks for infliximab

3. 10 weeks for adalimumab, certolizumab, and golimumab

4. 12 weeks for abatacept

• Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
• Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
• Prior documented history of no response to hydroxychloroquine and sulfasalazine
• Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's

medical management of RA):

1. 4 weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline

2. 12 weeks for leflunomide unless the subject has completed the following elimination procedure at least 4 weeks prior to baseline: Cholestyramine at a dosage of 8 grams 3 times daily for at least 24 hours, or activated charcoal at a dosage of 50 grams 4 times daily for at least 24 hours

3. 24 weeks for cyclophosphamide

• Vaccination with live vaccines in the 6 weeks prior to baseline or planned vaccination with live vaccines during the study
• Participation in any other investigational drug study within 30 days or 5 times the terminal half-life of the investigational drug, whichever is longer, prior to baseline
• Other treatments for RA (e.g., Prosorba Device/Column) within 6 months prior to baseline
• Use of intra-articular hyaluronic acid injections within 4 weeks prior to baseline
• Use of non steroidal anti inflammatory drugs (NSAIDs) on unstable dose or switching of NSAIDs within 2 weeks prior to baseline
• Previous participation in this study (randomized) or another study of OKZ
• Subjects with concurrent acute or chronic viral Hepatitis B or C infection as detected by blood tests at Screening (e.g., positive for hepatitis B surface antigen [HBsAg], total hepatitis B core antibody [anti-HBc], or hepatitis C virus antibody [HCV Ab]) a) subjects who are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible.
• Subjects with HIV infection
• Subjects with:

1. Suspected or confirmed current active tuberculosis (TB) disease or a history of active TB disease.

2. Close contact (i.e., sharing the same household or other enclosed environment, such as a social gathering place, workplace, or facility, for extended periods during the day) with an individual with active TB within 1.5 years prior to Screening

• Concurrent malignancy or a history of malignancy within the last 5 years (with the exception of successfully treated carcinoma of the cervix in situ and successfully treated basal cell carcinoma and squamous cell carcinoma not less than 1 year prior to Screening [and no more than 3 excised skin cancers within the last 5 years prior to Screening])
• Subjects with any infection requiring oral antibiotic or antiviral therapy in the 2 weeks prior to Screening or at baseline, injectable anti-infective therapy in the last 4 weeks prior to baseline, or serious or recurrent infection with history of hospitalization in the 6 months prior to baseline
• Subjects with evidence of disseminated herpes zoster infection, zoster encephalitis, meningitis, or other non-self-limited herpes zoster infections in the 6 months prior to baseline
• Subjects with planned surgery during the study or surgery = 4 weeks prior to Screening and from which the subject has not fully recovered, as judged by the Investigator
• Subjects with diverticulitis or other symptomatic GI conditions that might predispose the subject to perforations, including subjects with history of such predisposing conditions (e.g., diverticulitis, GI perforation, or ulcerative colitis)
• Pre-existing central nervous system demyelinating disorders (e.g., multiple sclerosis and optic neuritis)
• History of chronic alcohol or drug abuse as judged by the Investigator
• Subjects with a known hypersensitivity to any component of the OKZ drug product or placebo
• Subjects with a known hypersensitivity or contraindication to any component of the rescue medication
• History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Female subjects who are pregnant, currently lactating, have lactated within the last 12 weeks, or who are planning to become pregnant during the study or within 6 months of the last dose of study treatment
• Female subjects of childbearing potential (unless permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of natural amenorrhea as defined by the amenorrhea with underlying status [e.g., correlative age] or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly effective method of contraception during the study and for at least 6 months after the last administration of study treatment OR Male subjects with partners of childbearing potential not willing to use a highly effective method of contraception during the study and for at least 3 months after the last administration of study treatment. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Necrosis
• Rheumatoid Arthritis

Intervention

Drug:
• Olokizumab
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
• Placebo
sodium chloride 0.9% solution provided as either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule

Locations

Country	Name	City	State
Argentina	APRILLUS	Ciudad Autonoma Buenos aires
Argentina	Atencion Integral en Reumatologia (AIR)	Ciudad Autonoma Buenos Aires
Argentina	Instituto Centenario	Ciudad Autonoma Buenos Aires
Argentina	Organizacion Medica de Investigacion (OMI)	Ciudad Autonoma Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba S.A	Cordoba
Argentina	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires
Argentina	Clinica de Higado y Aparato Digestivo	Rosario	Santa Fe
Argentina	Centro Polivalente de Asistencia e Inv. Clinica CER	San Juan
Argentina	Centro de Investigaciones Reumatológicas	San Miguel de Tucuman	Tucuman
Argentina	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman
Argentina	Sanatorio San Martin	Venado Tuerto	Santa Fe
Brazil	CETI - Centro de Estudos em Terapias Inovadoras Ltda.	Curitiba	Paraná
Brazil	HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará	Fortaleza	Ceará
Brazil	CIP - Centro Internacional de Pesquisa	Goiânia	Goiás
Brazil	CMiP - Centro Mineiro de Pesquisa	Juiz de Fora	Minas Gerais
Brazil	Hospital Bruno Born	Lajeado	Rio Grande Do Sul
Brazil	LMK Serviços Médicos S/S Ltda	Porto Alegre	Rio Grande Do Sul
Brazil	Clínica de Neoplasias Litoral Ltda.	Santa Catarina
Brazil	Faculdade de Medicina do ABC	Santo André	Sao Paulo
Brazil	Centro Multidisciplinar de Estudos Clínicos - CEMEC	Sao Bernardo Do Campo	Sao Paulo
Brazil	Associação de Assistência à Criança Deficiente - AACD	Sao Paulo
Brazil	CPCLIN - Centro de Pesquisas Clínicas Ltda.	São Paulo
Brazil	CEDOES - Diagnóstico e Pesquisa	Vitória	Espírito Santo
Colombia	Centro de Reumatologia y Ortopedia SAS	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM	Bogotá
Colombia	Medicity S.A.S.	Bucaramanga
Colombia	Clinica de Artritis Temprana S.A.	Cali
Czechia	Revmatologie MUDr. Klara Sirova s.r.o.	Ostrava - Moravska Ostrava
Czechia	CCR Czech, a.s.	Pardubice
Czechia	MEDICAL PLUS s.r.o.	Uherske Hradiste
Czechia	PV - Medical, s.r.o.	Zlin
Germany	Kerckhoff-Klinik gGmbH	Bad Nauheim	Hessen
Germany	HRF Hamburger Rheuma Forschungszentrum	Hamburg
Germany	SMO.MD GmbH	Magdeburg	Sachsen Anhalt
Hungary	Clinexpert Egeszsegugyi Szolg. es Ker. Kft.	Budapest
Hungary	Obudai Egeszsegugyi Centrum	Budapest
Hungary	MAV Korhaz és Rendelointezet	Szolnok
Hungary	Vital Medical Center	Veszprem
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Hallym University Sacred Heart Hospital	Gyeonggi-do
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do
Mexico	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua
Mexico	Centro de Estudios de Investigacion Basica y Clinica SC	Guadalajara	Jalisco
Mexico	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco
Mexico	Centro de Investigacion Clínica GRAMEL S.C	Mexico	Distrito Federal
Mexico	Clinstile, S.A. de C.V.	Mexico	Distrito Federal
Mexico	Accelerium S. de R.L. de C.V.	Monterrey	Nuevo León
Mexico	Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo León
Mexico	Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.	San Luis Potosi	San Luis Potos
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	McBk S.C.	Grodzisk Mazowiecki
Poland	Centrum Medyczne AMED	Lodz
Poland	Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego	Sieradz
Poland	Samodzielny Publiczny ZOZ Tomaszow Lubelski	Tomaszow Lubelski
Poland	McM Polimedica	Warszawa
Russian Federation	FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"	Moscow
Russian Federation	State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department	Moscow	Moscow Region
Russian Federation	City Clinical Hospital #1	Novosibirsk	Novosibirsk Oblast
Russian Federation	Diagnostic Center Ultramed	Omsk	Omsk Oblast
Russian Federation	SBHI of the Republic of Karelia "Republican Hospital named after V.A.Baranov"	Petrozavodsk	Republic Of Karelia
Russian Federation	Rostov State Medical Unversity	Rostov-on-Don	Rostov Oblast
Russian Federation	SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"	Stavropol'	Stavropol Region
Russian Federation	Regional Clinical Hospital	Vladimir	Vladimir Oblast
United States	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico
United States	Amarillo Center for Clinical Research	Amarillo	Texas
United States	Austin Regional Clinic, P.A.	Austin	Texas
United States	Accurate Clinical Research, Inc.	Baytown	Texas
United States	RASF - Clinical Research Center	Boca Raton	Florida
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	Low Country Research Center	Charleston	South Carolina
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Medvin Clinical Research	Covina	California
United States	STAT Research, Inc.	Dayton	Ohio
United States	Denver Arthritis Clinic	Denver	Colorado
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Arthritis & Osteoporosis Associates, PA	Freehold	New Jersey
United States	Saint Jude Heritage Medical Grp	Fullerton	California
United States	Precision Comprehensive Clinical Research Solutions	Grapevine	Texas
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Klein and Associates, M.D., P.A.	Hagerstown	Maryland
United States	? V Mehta MD Med Corp.	Hemet	California
United States	CHI St. Vincent Hot Springs	Hot Springs	Arkansas
United States	Accurate Clinical Research, Inc.	Houston	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	Rheumatology Clinic of Houston, P.A.	Houston	Texas
United States	Therapeutic Concepts Rheumatology, LLC	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	Glacier View Research Instutute-Rheumatology	Kalispell	Montana
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Advanced Medical Research, LLC	Lakewood	California
United States	Accurate Clinical Research, Inc.	League City	Texas
United States	Cape Fear Arthritis Care	Leland	North Carolina
United States	Endocrinology, Internal Medicine	Lubbock	Texas
United States	Suncoast Research Group LLC	Miami	Florida
United States	Trinity Medical Group	Minot	North Dakota
United States	The Arthritis & Diabetes Clinic, Inc.	Monroe	Louisiana
United States	NYU Langone Ambulatory Care	New York	New York
United States	Javed Rheumatology Associates	Newark	Delaware
United States	Omega Research Consultants	Orlando	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Family Clinical Trials, LLC.	Pembroke Pines	Florida
United States	Clinical Research Source, Inc.	Perrysburg	Ohio
United States	Arthritis Group	Philadelphia	Pennsylvania
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona
United States	Riverside Medical Clinic	Riverside	California
United States	Dr. Alex De Jesus Rheumatology, P.A.	San Antonio	Texas
United States	East Bay Rheumatology Medical Group, Inc.	San Leandro	California
United States	AdventHealth Medical Group, PA	Tampa	Florida
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Carolina Arthritis Associates	Wilmington	North Carolina
United States	Advanced Rheumatology of Houston	Woodville	Texas
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
R-Pharm International, LLC	Mene Research, OCT Clinical Trials, Quintiles, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Colombia,  Czechia,  Germany,  Hungary,  Korea, Republic of,  Mexico,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response	The difference between OKZ and placebo in the percentage of subjects achieving an ACR20 response and remaining on randomized treatment and in the study at Week 12. A responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12.; American College of Rheumatology 20 % response is a composite defined as a = 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a =20% improvement from baseline in at least 3 of the 5 remaining core set measures: Patient Global Assessment of Disease Activity (VAS); Patient Assessment of Pain (VAS); HAQ-DI; Physician Global Assessment (VAS); Level of acute phase reactant (CRP)	at Week 12
Secondary	Percentage of Subjects Achieving Low Disease Activity	Defined as Disease Activity Score 28-joint count (DAS28) C-reactive protein (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12	at Week 12
Secondary	Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)	Change of physical ability from baseline (the last available assessment prior to the first dose of the study treatment) to week 12, as measured by HAQ-DI. The HAQ-DI assesses the degree of difficulty experienced in 8 domains of daily living activities using 20 questions.The domains are dressing and grooming, arising, eating, walking, hygiene, reach, grip and common daily activities, and each domain consists of 2 or 3 items. For each question, the level of difficulty is scored from 0 to 3 where 0 = without any difficulty (the best outcome), 1 = with some difficulty, 2 = much difficulty, and 3 = unable to do (the worst outcome). Each category is given a score by taking the maximum score of each question. A decrease from baseline indicates improvement for HAQ-DI.The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered. The HAQ-DI total score ranges from 0 (the best outcome) to 3 (the worst outcome).	Baseline to Week 12
Secondary	Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response	Difference between OKZ and placebo in the percentage of subjects achieving an ACR50 response and remaining on randomized treatment and in the study at Week 12.; American College of Rheumatology 50% Response is a composite defined as =50%, improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a =50%, improvement from baseline in at least 3 of the 5 remaining core set measures: Patient Global Assessment of Disease Activity (VAS); Patient Assessment of Pain (VAS); HAQ-DI; Physician Global Assessment (VAS); Level of acute phase reactant (CRP)	at Week 12
Secondary	Percentage of Subjects With Clinical Disease Activity Index (CDAI) = 2.8 (Remission)	Difference between OKZ and placebo in the percentage of subjects with Clinical Disease Activity Index (CDAI) =2.8 (remission) and remaining on randomized treatment and in the study at Week 12	at Week 12