Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo and Adalimumab, in Subjects With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Have Active Disease

Rheumatoid Arthritis Clinical Trial

— CREDO 2  

Official title:

A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02760407
• Other study ID #: CL04041023
• Status: Completed
• Phase: Phase 3
• Start date: June 6, 2016
• Est. completion date: November 5, 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 methotrexate (MTX).

The primary objective of this study was to evaluate the efficacy of 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 RA inadequately controlled by MTX therapy.

The secondary objective was to evaluate the efficacy of OKZ relative to adalimumab in subjects with moderately to severely active RA inadequately controlled by MTX 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 MTX. The primary endpoint of the trial was 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 study included a 4-week Screening Period, a double-blind Treatment Period from Week 0 to Week 24, and a Safety Follow-Up Period from Week 24 to Week 44. Subjects were assessed for eligibility to enter the study during the 4-week Screening Period. A total of 1575 subjects were planned to be randomly assigned to 1 of 4 treatment groups in a 2:2:2:1 ratio (450, 450, 450, and 225 subjects per group, respectively):

1. Olokizumab 64 mg q4w: SC injection of OKZ 64 mg q4w (alternating with SC injection of placebo q4w to maintain blinding) + MTX

2. Olokizumab 64 mg q2w: SC injection of OKZ 64 mg q2w + MTX

3. Adalimumab 40 mg q2w: SC injection of adalimumab 40 mg q2w + MTX

4. Placebo: SC injection of placebo q2w + MTX

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 study treatment (OKZ, adalimumab, or placebo) was at Week 22 in all groups.

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 had not improved 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 had 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 208 sites across 18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1648
• Est. completion date: November 5, 2019
• Est. primary completion date: August 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion 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 12 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)

• Inadequate response to treatment with oral, SC, or intramuscular MTX (defined as a subject with at least 12 weeks of exposure prior to Screening and with either absence of any documented clinically significant response, or documented initial clinical response with subsequent loss of that response or partial response) for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or =10 mg/week if intolerant to higher doses). The dose and route of administering MTX had to have been stable for at least 6 weeks prior to Screening. A lower dose of MTX (=7.5 mg/week) was permitted for subjects enrolled in the Republic of Korea, consistent with local clinical practice.

• 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

• CRP above the normal range (ULN) at Screening based on the central laboratory results.

Exclusion Criteria:

• Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (eg, gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus). However, subjects could 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 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)

• Prior use of bDMARDs

• 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]). Subjects who are are positive for hepatitis B surface antibodies (anti-HBs), but negative for HBsAg and anti-HBc, will be eligible

• Subjects with human immunodeficiency virus (HIV) infection

• Subjects with:

1. Suspected or confirmed current active 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

• 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 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.

• Subjects with a known hypersensitivity to any component of the OKZ drug product, adalimumab, 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

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
• Rheumatoid Arthritis

Intervention

Drug:
• Olokizumab 64mg q4w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
• Olokizumab 64mg q2w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
• Adalimumab 40mg q2w
0.4 or 0.8 mL prefilled, single-dose syringe
• Placebo q2w
sodium chloride 0.9% solution supplied in 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	Institute Investigaciones Clinc Quilme	Buenos Aires
Argentina	APRILLUS Asistencia e Investigacion	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	Instituto DAMIC Fundacion Rusculleda	Cordoba
Argentina	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas-Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto Medico CER	Quilmes	Buenos Aires
Argentina	Clinica de Higado y Aparato Digestivo	Rosario	Santa Fe
Argentina	CER San Juan Centro Polivalente de Asistencia e Inv. Clinica	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	Clinilive - Clínica do Idoso e Pesquisa Clínica	Maringá	Paraná
Brazil	LMK Serviços Médicos S/S Ltda	Porto Alegre	Rio Grande Do Sul
Brazil	CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.	Rio de Janeiro
Brazil	Clínica de Neoplasias Litoral	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	CPCLIN - Centro de Pesquisas Clínicas Ltda.	São Paulo
Brazil	Hospital Abreu Sodré - AACD	São Paulo
Brazil	CEDOES - Diagnóstico e Pesquisa	Vitória	Espírito Santo
Bulgaria	UMHAT Pulmed OOD	Plovdiv
Bulgaria	MHAT - Ruse, AD	Ruse
Bulgaria	Medizinski Zentar-1-Sevlievo EOOD	Sevlievo
Bulgaria	MHAT - Shumen, AD	Shumen
Bulgaria	MC Synexus - Sofia EOOD	Sofia
Bulgaria	Medical Center "Excelsior", OOD	Sofia
Bulgaria	MHAT "Lyulin", EAD	Sofia
Bulgaria	NMTH "Tsar Boris III"	Sofia
Bulgaria	UMHAT Sv. Ivan Rilski EAD	Sofia
Bulgaria	MDHAT 'Dr. Stefan Cherkezov', AD	Veliko Tarnovo
Colombia	Centro de Investigacion Medico	Barranquilla	Atlantico
Colombia	Fundacion Instituto de Reumatologia Fernando Chalem	Bogota
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	CCR Brno s.r.o	Brno
Czechia	Revmatologie s.r.o.	Brno
Czechia	Nemocnice Jihlava p.o	Jihlava
Czechia	MUDr. Gabriela Simkova ordinace lekare specialisty interna revmatologie	Kladno
Czechia	CTCenter MaVe s.r.o.	Olomouc
Czechia	Vesalion s.r.o.	Ostrava
Czechia	Artroscan s.r.o.	Ostrava - Trebovice
Czechia	ARTHROHELP s.r.o.	Pardubice
Czechia	CCR Pardubice	Pardubice
Czechia	Affidea Praha, s.r.o.	Praha
Czechia	Revmatologicky ustav	Praha
Czechia	Clintrial, s.r.o.	Praha 10
Czechia	CCR Prague s.r.o.	Praha 3
Czechia	MUDR. Zuzana Urbanova Revmatologie	Praha 4
Czechia	MUDR. Zuzana URBANOVA Revmatologie	Praha 4 Nusle
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	MEDICAL PLUS s.r.o.	Uherske Hradiste
Czechia	PV Medical Services s.r.o.	Zlin
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Medita Kliinik OÜ	Tartu
Germany	Rheumapraxis Dr. med. Reiner Kurthen	Aachen	Westfalen
Germany	Kerckhoff-Klinik gGmbH	Bad Nauheim	Hessen
Germany	Klinische Forschung Berlin-Mitte GmbH	Berlin
Germany	HRF Hamburger Rheuma Forschungszentrum	Hamburg
Germany	SMO.MD GmbH	Magdeburg	Sachsen Anhalt
Germany	Studienambulanz Dr. Wassenberg	Northeim
Hungary	Principal SMO Kft.	Baja
Hungary	DRC Gyogyszervizsgalo Kozpont Kft.	Balatonfured
Hungary	Clinexpert Egeszsegugyi Szolg. es Ker. Kft.	Budapest
Hungary	Obudai Egeszsegugyi Centrum	Budapest
Hungary	Kiskunhalasi Semmelweis Korhaz	Kiskunhalas
Hungary	DRC Szekesfehervar	Szekesfehervar
Hungary	MAV Korhaz és Rendelointezet	Szolnok
Hungary	Vital Medical Center	Veszprem
Korea, Republic of	Eulji University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Jeju National University Hospital	Jeju
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Latvia	Dr.Saulite-Kandevica Private Practice	Liepaja
Lithuania	Alyt?us Regional S. Kudirkos Hospital, Public Institution	Alytus
Lithuania	Republican Kaunas Hospital, Public Institution	Kaunas
Lithuania	Klaipeda University Hospital, Public Institution	Klaipeda
Lithuania	Siauliai Republican Hospital, Public Institution	Siauliai
Lithuania	Center Outpatient Clinic, Public Institution	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinic, Public Institution	Vilnius
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	DisMexicotrito Federal
Mexico	Clinicos Asociados BOCM S.C.	Mexico	Distrito Federal
Mexico	Clinstile, S.A. de C.V.	Mexico	Distrito Federal
Mexico	Cryptex Investigacion Clinica S.C	Mexico	Distrito Federal
Mexico	Clinical Research Institute S.C.	Mexico City	Estado De Mexico
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
Poland	NZOZ ZDROWIE Osteo-Medic	Bialystok
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	MCBK Iwona Czajkowska Anna PodrazkaSzczepaniak S.C.	Grodzisk Mazowiecki
Poland	Polimedica Centrum Badan, Profilaktyki I Leczenia	Kielce
Poland	Centrum Medyczne AMED	Lodz
Poland	ETYKA Osrodek Badan Klinicznych	Olsztyn
Poland	Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego	Sieradz
Poland	CCBR - Lodz - PL	Skierniewice
Poland	Clinmed Research	Skierniewice
Poland	RCMed	Sochaczew
Poland	KO-MED Centra Kliniczne Staszow	Staszow
Poland	Samodzielny Publiczny ZOZ Tomaszow Lubelski	Tomaszow Lubelski
Poland	Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z	Torun
Poland	McM Polimedica	Warszawa
Poland	Medycyna Kliniczna	Warszawa
Poland	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa
Poland	KO-MED Centra Kliniczne Zamosc	Zamosc
Poland	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Zgierz
Romania	Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta	Constanta
Russian Federation	SBEI HPE "Ural State Medical University" of MoH of RF based MBI "Central City Clinical Hospital #6"	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	State Budgetary Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital #1"	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	FSBEI HE "FMSMU n.a. I.M. Sechenov of MoH of RF", University Hospital #2, Departament of New Drugs Introduction	Moscow	Moscovskaya Oblast
Russian Federation	Institute n 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	SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	SBHI of Republic of Karelia "Republican Hospital named after V.A.Baranov"	Petrozavodsk	Republic Of Karelia
Russian Federation	SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit	Saint Petersburg	Leningradskaya Oblast
Russian Federation	Non-govarnmental Healtheare Institution "Regional Clinical Hospital at Smolensk station of OJSC "Russian Railways"	Smolensk	Smolenskaya Oblast
Russian Federation	Hospital n a Kuvatov	Ufa	Republic Of Bashkortostan
Taiwan	Chi Mei Medical Center	Tainan
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke	Hampshire
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	Whipps Cross University Hospital	London	Greater London
United Kingdom	Maidstone Hospital	Maidstone	Kent
United Kingdom	Torbay Hospital	Torquay	Devon
United Kingdom	Arrowe Park Hospital	Wirral	Merseyside
United States	Amarillo Center for Clinical Research	Amarillo	Texas
United States	Austin Regional Clinic, P.A.	Austin	Texas
United States	Accurate Clinical Management LLC	Baytown	Texas
United States	Pioneer Research Solutions, Inc.	Beaumont	Texas
United States	RASF - Clinical Research Center	Boca Raton	Florida
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	New England Research Associates LLC	Bridgeport	Connecticut
United States	NYU Langone ambulatory care	Brooklyn	New York
United States	Medvin Clinical Research	Covina	California
United States	STAT Research, Inc.	Dayton	Ohio
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Altoona Center for Clinical Research, P.C.	Duncansville	Pennsylvania
United States	TriWest Research Associates	El Cajon	California
United States	Arthritis & Osteoporosis Associates, PA	Freehold	New Jersey
United States	Arthritis Center of North Georgia	Gainesville	Georgia
United States	AA MRC LLC Ahmed Arif Medical Research Center	Grand Blanc	Michigan
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	MD Med Corp.	Hemet	California
United States	Reliable Clinical Research, LLC	Hialeah	Florida
United States	Accurate Clinical Mangemnt LLC	Houston	Texas
United States	Accurate Clinical Research	Houston	Texas
United States	Accurate Clinical Research, Inc.	Houston	Texas
United States	Advanced Rheumatology of Houston	Houston	Texas
United States	Rheumatology Clinic of Houston, P.A.	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	Accurate Clinical Research, Inc.	League City	Texas
United States	Cape Fear Arthritis Care	Leland	North Carolina
United States	Physician Resrch Collaboration	Lincoln	Nebraska
United States	Valerius Medical Group	Los Alamitos	California
United States	Endocrinology, Internal Medicine	Lubbock	Texas
United States	Marietta Rheumatology Associates, PC	Marietta	Georgia
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Mesa	Arizona
United States	Medical Research Center of Miami	Miami	Florida
United States	Pharmax Research Clinic, Inc.	Miami	Florida
United States	Trinity Medical Group	Minot	North Dakota
United States	The Arthritis & Diabetes Clinic, Inc.	Monroe	Louisiana
United States	Javed Rheumatology Associates	Newark	Delaware
United States	Health Research of Oklahoma, PLLC	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Omega Research Consultants	Orlando	Florida
United States	Arthritis Research	Palm Harbor	Florida
United States	Family Clinical Trials, LLC.	Pembroke Pines	Florida
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona
United States	Dr. Alex De Jesus Rheumatology, P.A.	San Antonio	Texas
United States	Rheumatology Center of San Diego	San Diego	California
United States	East Bay Rheumatology Medical Group, Inc.	San Leandro	California
United States	Pacific Arthritis Center Medical Grpoup	Santa Maria	California
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Springfield Clinic, LLP	Springfield	Illinois
United States	Low Country Rheumatology, PA	Summerville	South Carolina
United States	Arizona Arthritis & Rheumatology Research, PLLC	Sun City	Arizona
United States	AdventHealth Medical Group, PA	Tampa	Florida
United States	Clinical Research Source, Inc.	Toledo	Ohio
United States	DM Clinical Research	Tomball	Texas
United States	North MS Medical Clinics, Inc.	Tupelo	Mississippi
United States	Inland Rheumatology Clinical Trials	Upland	California
United States	Lovelace Scientific Resources, Inc.	Venice	Florida
United States	Center for Rheumatology Research	West Hills	California
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Medvin Clinical Research	Whittier	California

Sponsors (3)

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

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Colombia,  Czechia,  Estonia,  Germany,  Hungary,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Poland,  Romania,  Russian Federation,  Taiwan,  United Kingdom, 

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. (where a responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12) This endpoint served to demonstrate that the efficacy of OKZ was superior to placebo. 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 ACR20 Response: Olokizumab Comparison With Adalimumab	A responder was defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12.This endpoint served to demonstrate that the efficacy of OKZ was non-inferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) was demonstrated concurrently based on the same endpoint.; 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	Percentage of Subjects Achieving Low Disease Activity: Olokizumab Comparison With Adalimumab	Percentage of subjects achieving low disease activity, defined as DAS28 (CRP) <3.2, and remaining on randomized treatment and in the study at Week 12; served to demonstrate that the efficacy of OKZ was noninferior to adalimumab, provided that superiority of adalimumab to placebo (assay sensitivity) was demonstrated concurrently based on the same endpoint	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 24; 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 24
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 24	at Week 24