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 (CREDO 2)

September 19, 2023 updated by: R-Pharm International, LLC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Interventional

Enrollment (Actual)

1648

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, B1878GEG
        • Institute Investigaciones Clinc Quilme
      • Ciudad Autonoma Buenos Aires, Argentina, C1015ABO
        • Organizacion Medica de Investigacion (OMI)
      • Ciudad Autonoma Buenos Aires, Argentina, C1204AAD
        • Instituto centenario
      • Ciudad Autonoma Buenos Aires, Argentina, 1426
        • Atencion Integral en Reumatologia (AIR)
      • Ciudad Autonoma Buenos aires, Argentina, C1046AAQ
        • APRILLUS Asistencia E Investigacion
      • Cordoba, Argentina, X5003DCE
        • Instituto DAMIC Fundacion Rusculleda
      • Cordoba, Argentina, 5016
        • Hospital Privado Centro Medico de Cordoba S.A
      • San Juan, Argentina, 5400
        • CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
    • Buenos Aires
      • Mar del Plata, Buenos Aires, Argentina, B7600FYK
        • Centro de Investigaciones Medicas Mar del Plata
      • Mar del Plata, Buenos Aires, Argentina, B7600FZN
        • Instituto de Investigaciones Clinicas-Mar del Plata
      • Quilmes, Buenos Aires, Argentina, B1878DVB
        • Instituto Médico Cer
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000CFJ
        • Clinica de Higado y Aparato Digestivo
      • Venado Tuerto, Santa Fe, Argentina, S2600KUE
        • Sanatorio San Martin
    • Tucuman
      • San Miguel de Tucuman, Tucuman, Argentina, T4000AXL
        • Centro Medico Privado de Reumatologia
      • San Miguel de Tucuman, Tucuman, Argentina, T4000BRD
        • Centro de Investigaciones Reumatológicas
  • Brazil
      • Rio de Janeiro, Brazil, 20241-180
        • CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.
      • Santa Catarina, Brazil, 88301-215
        • Clinica de Neoplasias Litoral
      • São Paulo, Brazil, 01228-200
        • CPCLIN - Centro de Pesquisas Clínicas Ltda.
      • São Paulo, Brazil, 04032-060
        • Hospital Abreu Sodré - AACD
    • Ceará
      • Fortaleza, Ceará, Brazil, 60430-370
        • HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29055450
        • CEDOES - Diagnóstico e Pesquisa
    • Goiás
      • Goiânia, Goiás, Brazil, 74110-120
        • CIP - Centro Internacional de Pesquisa
    • Minas Gerais
      • Juiz de Fora, Minas Gerais, Brazil, 36010-570
        • CMiP - Centro Mineiro de Pesquisa
    • Paraná
      • Curitiba, Paraná, Brazil, 80030-110
        • CETI - Centro de Estudos em Terapias Inovadoras Ltda.
      • Maringá, Paraná, Brazil, 87013-250
        • Clinilive - Clínica do Idoso e Pesquisa Clínica
    • Rio Grande Do Sul
      • Lajeado, Rio Grande Do Sul, Brazil, 95900-010
        • Hospital Bruno Born
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90480-000
        • LMK Serviços Médicos S/S Ltda
    • Sao Paulo
      • Santo André, Sao Paulo, Brazil, 09060-650
        • Faculdade de Medicina do ABC
      • Sao Bernardo Do Campo, Sao Paulo, Brazil, 09715-090
        • Centro Multidisciplinar de Estudos Clínicos - CEMEC
  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • UMHAT Pulmed OOD
      • Ruse, Bulgaria, 7002
        • MHAT - Ruse, AD
      • Sevlievo, Bulgaria, 5400
        • Medizinski Zentar-1-Sevlievo EOOD
      • Shumen, Bulgaria, 9700
        • MHAT - Shumen, AD
      • Sofia, Bulgaria, 1233
        • NMTH "Tsar Boris III"
      • Sofia, Bulgaria, 1336
        • MHAT "Lyulin", EAD
      • Sofia, Bulgaria, 1431
        • Umhat Sv. Ivan Rilski Ead
      • Sofia, Bulgaria, 1407
        • Medical Center "Excelsior", OOD
      • Sofia, Bulgaria, 1784
        • MC Synexus - Sofia EOOD
      • Veliko Tarnovo, Bulgaria, 5000
        • MDHAT 'Dr. Stefan Cherkezov', AD
  • Colombia
      • Bogota, Colombia, 111211
        • Fundacion Instituto de Reumatologia Fernando Chalem
      • Bogotá, Colombia, 110221
        • Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
      • Bucaramanga, Colombia, 680003
        • Medicity S.A.S.
      • Cali, Colombia, 76001
        • Clinica de Artritis Temprana S.A.
    • Atlantico
      • Barranquilla, Atlantico, Colombia, 080020
        • Centro de Investigacion Medico
  • Czechia
      • Brno, Czechia, 638 00
        • Revmatologie s.r.o.
      • Brno, Czechia, 60200
        • CCR Brno s.r.o
      • Jihlava, Czechia, 586 01
        • Nemocnice Jihlava p.o
      • Kladno, Czechia, 272 01
        • MUDr. Gabriela Simkova ordinace lekare specialisty interna revmatologie
      • Olomouc, Czechia, 77900
        • CTCenter MaVe s.r.o.
      • Ostrava, Czechia, 70200
        • Vesalion s.r.o.
      • Ostrava - Trebovice, Czechia, 722 00
        • Artroscan s.r.o.
      • Pardubice, Czechia, 530 02
        • Arthrohelp S.R.O.
      • Pardubice, Czechia, 530 02
        • CCR Pardubice
      • Praha, Czechia, 148 00
        • Affidea Praha, s.r.o.
      • Praha, Czechia, 128 00
        • Revmatologicky Ustav
      • Praha 10, Czechia, 100 00
        • CLINTRIAL, s.r.o.
      • Praha 3, Czechia, 130 00
        • CCR Prague s.r.o.
      • Praha 4, Czechia, 140 00
        • MUDR. Zuzana URBANOVA Revmatologie
      • Praha 4 Nusle, Czechia, 140 00
        • MUDR. Zuzana URBANOVA Revmatologie
      • Praha 5, Czechia, 150 06
        • Fakultni nemocnice v Motole
      • Uherske Hradiste, Czechia, 686 01
        • MEDICAL Plus s.r.o.
      • Zlin, Czechia, 760 01
        • PV Medical Services s.r.o.
  • Estonia
      • Tallinn, Estonia, 11312
        • East Tallinn Central Hospital
      • Tartu, Estonia, 50406
        • Medita Kliinik OÜ
  • Germany
      • Berlin, Germany, 10117
        • Klinische Forschung Berlin-Mitte GmbH
      • Hamburg, Germany, 20095
        • HRF Hamburger Rheuma Forschungszentrum
      • Northeim, Germany, 40878
        • Studienambulanz Dr. Wassenberg
    • Hessen
      • Bad Nauheim, Hessen, Germany, 61231
        • Kerckhoff-Klinik gGmbH
    • Sachsen Anhalt
      • Magdeburg, Sachsen Anhalt, Germany, 39120
        • SMO.MD GmbH
    • Westfalen
      • Aachen, Westfalen, Germany, 52064
        • Rheumapraxis Dr. med. Reiner Kurthen
  • Hungary
      • Baja, Hungary, 6500
        • Principal SMO Kft.
      • Balatonfured, Hungary, 8230
        • DRC Gyogyszervizsgalo Kozpont Kft.
      • Budapest, Hungary, 1036
        • Óbudai Egészségügyi Centrum
      • Budapest, Hungary, 1033
        • Clinexpert Egeszsegugyi Szolg. es Ker. Kft.
      • Kiskunhalas, Hungary, 6400
        • Kiskunhalasi Semmelweis Korhaz
      • Szekesfehervar, Hungary, 8000
        • DRC Szekesfehervar
      • Szolnok, Hungary, 5000
        • MAV Korhaz es Rendelointezet
      • Veszprem, Hungary, 8200
        • Vital Medical Center
  • Korea, Republic of
      • Daejeon, Korea, Republic of, 35233
        • Eulji University Hospital
      • Gwangju, Korea, Republic of, 61469
        • Chonnam National University Hospital
      • Gyeonggi-do, Korea, Republic of, 13496
        • CHA Bundang Medical Center
      • Jeju, Korea, Republic of, 63241
        • Jeju National University Hospital
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University
  • Latvia
      • Liepaja, Latvia, LV-3401
        • Dr.Saulite-Kandevica Private Practice
  • Lithuania
      • Alytus, Lithuania, 62114
        • Alytаus Regional S. Kudirkos Hospital, Public Institution
      • Kaunas, Lithuania, 45130
        • Republican Kaunas Hospital, Public Institution
      • Klaipeda, Lithuania, 92288
        • Klaipeda University Hospital, Public Institution
      • Siauliai, Lithuania, 76231
        • Siauliai Republican Hospital, Public Institution
      • Vilnius, Lithuania, LT-08661
        • Vilnius University Hospital Santariskiu Clinic, Public Institution
      • Vilnius, Lithuania, LT-01117
        • Center Outpatient Clinic, Public Institution
  • Mexico
      • Chihuahua, Mexico, 31000
        • Investigacion y Biomedicina de Chihuahua, S.C.
      • San Luis Potosi, Mexico, 78213
        • Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.
    • DisMexicotrito Federal
      • Mexico, DisMexicotrito Federal, Mexico, 03720
        • Centro de Investigacion Clínica GRAMEL S.C
    • Distrito Federal
      • Mexico, Distrito Federal, Mexico, 3300
        • Clinicos Asociados BOCM S.C.
      • Mexico, Distrito Federal, Mexico, 06700
        • Clinstile, S.A. de C.V.
      • Mexico, Distrito Federal, Mexico, 6100
        • Cryptex Investigacion Clinica S.C
    • Estado De Mexico
      • Mexico City, Estado De Mexico, Mexico, 54055
        • Clinical Research Institute S.C.
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44650
        • Clinica de Investigacion en Reumatologia y Obesidad S.C.
      • Guadalajara, Jalisco, Mexico, 44690
        • Centro de Estudios de Investigacion Basica Y Clinica SC
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64000
        • Accelerium S. de R.L. de C.V.
      • Monterrey, Nuevo León, Mexico, 64460
        • Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
  • Poland
      • Bialystok, Poland, 15-351
        • Nzoz Zdrowie Osteo-Medic
      • Bydgoszcz, Poland, 85-168
        • Szpital Uniwersytecki nr 2 im.dr J. Biziela
      • Grodzisk Mazowiecki, Poland, 05-825
        • MCBK Iwona Czajkowska Anna PodrażkaSzczepaniak S.C.
      • Kielce, Poland, 25-355
        • Polimedica Centrum Badań, Profilaktyki I Leczenia
      • Lodz, Poland, 91-363
        • Centrum Medyczne AMED
      • Olsztyn, Poland, 10-117
        • ETYKA Osrodek Badan Klinicznych
      • Sieradz, Poland, 98-200
        • Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
      • Skierniewice, Poland, 96-100
        • Clinmed Research
      • Skierniewice, Poland, 90 368
        • CCBR - Lodz - PL
      • Sochaczew, Poland, 96-500
        • RCMed
      • Staszow, Poland, 28-200
        • KO-MED Centra Kliniczne Staszow
      • Tomaszow Lubelski, Poland, 22-600
        • Samodzielny Publiczny ZOZ Tomaszow Lubelski
      • Torun, Poland, 87-100
        • Niepubliczny Zaklad Opieki Zdrowotnej "Nasz Lekarz" Praktyka Grupowa Lekarzy Rodzinnych z
      • Warszawa, Poland, 00-874
        • Medycyna Kliniczna
      • Warszawa, Poland, 02-118
        • Rheuma Medicus Zaklad Opieki Zdrowotnej
      • Warszawa, Poland, 02-777
        • McM Polimedica
      • Zamosc, Poland, 22-400
        • KO-MED Centra Kliniczne Zamosc
      • Zgierz, Poland, 95-100
        • SANTA FAMILIA Centrum Badan, Profilaktyki i Leczenia
  • Romania
      • Constanta, Romania, 900591
        • Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
  • Russian Federation
      • Moscow, Russian Federation, 115522
        • Institute n a Nasonova
    • Leningradskaya Oblast
      • Saint Petersburg, Leningradskaya Oblast, Russian Federation, 190068
        • SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit
    • Moscovskaya Oblast
      • Moscow, Moscovskaya Oblast, Russian Federation, 119435
        • FSBEI HE "FMSMU n.a. I.M. Sechenov of MoH of RF", University Hospital #2, Departament of New Drugs Introduction
    • Moscow Region
      • Moscow, Moscow Region, Russian Federation, 111539
        • State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
    • Nizhegorodskaya Oblast
      • Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603126
        • SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"
    • Republic Of Bashkortostan
      • Ufa, Republic Of Bashkortostan, Russian Federation, 450005
        • Hospital n a Kuvatov
    • Republic Of Karelia
      • Petrozavodsk, Republic Of Karelia, Russian Federation, 185019
        • SBHI of Republic of Karelia "Republican Hospital named after V.A.Baranov"
    • Smolenskaya Oblast
      • Smolensk, Smolenskaya Oblast, Russian Federation, 214025
        • Non-govarnmental Healtheare Institution "Regional Clinical Hospital at Smolensk station of OJSC "Russian Railways"
    • Sverdlovskaya Oblast
      • Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620102
        • State Budgetary Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital #1"
      • Ekaterinburg, Sverdlovskaya Oblast, Russian Federation, 620149
        • SBEI HPE "Ural State Medical University" of MoH of RF based MBI "Central City Clinical Hospital #6"
  • Taiwan
      • Tainan, Taiwan, 710
        • Chi Mei Medical Center
      • Taoyuan, Taiwan, 333
        • Chang Gung Memorial Hospital, Linkou
  • United Kingdom
    • Devon
      • Torquay, Devon, United Kingdom, TQ2 7AA
        • Torbay Hospital
    • Greater London
      • London, Greater London, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, Greater London, United Kingdom, E11 1NR
        • Whipps Cross University Hospital
    • Hampshire
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Basingstoke and North Hampshire Hospital
    • Kent
      • Maidstone, Kent, United Kingdom, ME16 9QQ
        • Maidstone Hospital
    • Merseyside
      • Wirral, Merseyside, United Kingdom, CH49 5PE
        • Arrowe Park Hospital
  • United States
    • Arizona
      • Mesa, Arizona, United States, 85210
        • Arizona Arthritis & Rheumatology Associates, P.C.
      • Phoenix, Arizona, United States, 85032
        • Arizona Arthritis & Rheumatology Associates, P.C.
      • Sun City, Arizona, United States, 85351
        • Arizona Arthritis & Rheumatology Research, PLLC
    • California
      • Covina, California, United States, 91722
        • Medvin Clinical Research
      • El Cajon, California, United States, 92020
        • TriWest Research Associates
      • Hemet, California, United States, 92543
        • MD Med Corp.
      • Los Alamitos, California, United States, 90720-5403
        • Valerius Medical Group
      • San Diego, California, United States, 92128
        • Rheumatology Center of San Diego
      • San Leandro, California, United States, 94578
        • East Bay Rheumatology Medical Group, Inc.
      • Santa Maria, California, United States, 93454
        • Pacific Arthritis Center Medical Grpoup
      • Upland, California, United States, 91786
        • Inland Rheumatology Clinical Trials
      • West Hills, California, United States, 91607
        • Center for Rheumatology Research
      • Whittier, California, United States, 90602
        • Medvin Clinical Research
    • Colorado
      • Denver, Colorado, United States, 80230
        • Denver Arthritis Clinic
    • Connecticut
      • Bridgeport, Connecticut, United States, 6606
        • New England Research Associates LLC
    • Delaware
      • Newark, Delaware, United States, 19713
        • Javed Rheumatology Associates
    • Florida
      • Boca Raton, Florida, United States, 33486
        • RASF - Clinical Research Center
      • Hialeah, Florida, United States, 33012
        • Reliable Clinical Research, LLC
      • Miami, Florida, United States, 33126
        • Pharmax Research Clinic, Inc.
      • Miami, Florida, United States, 33134
        • Medical Research Center of Miami
      • Orlando, Florida, United States, 32810
        • Omega Research Consultants
      • Palm Harbor, Florida, United States, 34684
        • Arthritis Research
      • Pembroke Pines, Florida, United States, 33026
        • Family Clinical Trials, LLC.
      • Tampa, Florida, United States, 33614
        • AdventHealth Medical Group, PA
      • Venice, Florida, United States, 34292
        • Lovelace Scientific Resources, Inc.
    • Georgia
      • Gainesville, Georgia, United States, 30501
        • Arthritis Center of North Georgia
      • Marietta, Georgia, United States, 30060
        • Marietta Rheumatology Associates, PC
    • Idaho
      • Idaho Falls, Idaho, United States, 83404
        • Institute of Arthritis Research
    • Illinois
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic, LLP
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Hospital
    • Kentucky
      • Bowling Green, Kentucky, United States, 42101
        • Graves Gilbert Clinic
    • Louisiana
      • Monroe, Louisiana, United States, 71203
        • The Arthritis & Diabetes Clinic, Inc.
    • Maryland
      • Hagerstown, Maryland, United States, 21740
        • Klein and Associates, M.D., P.A.
      • Wheaton, Maryland, United States, 20902
        • The Center for Rheumatology and Bone Research
    • Michigan
      • Grand Blanc, Michigan, United States, 48439
        • AA MRC LLC Ahmed Arif Medical Research Center
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • North MS Medical Clinics, Inc.
    • Montana
      • Kalispell, Montana, United States, 59901
        • Glacier View Research Instutute-Rheumatology
    • Nebraska
      • Lincoln, Nebraska, United States, 68516
        • Physician Resrch Collaboration
    • New Jersey
      • Freehold, New Jersey, United States, 07728
        • Arthritis & Osteoporosis Associates, PA
    • New York
      • Brooklyn, New York, United States, 11201
        • NYU Langone Ambulatory Care
    • North Carolina
      • Greensboro, North Carolina, United States, 27408
        • Medication Management, LLC
      • Leland, North Carolina, United States, 28451
        • Cape Fear Arthritis Care
    • North Dakota
      • Minot, North Dakota, United States, 58701
        • Trinity Medical Group
    • Ohio
      • Dayton, Ohio, United States, 45417
        • STAT Research, Inc.
      • Toledo, Ohio, United States, 43606
        • Clinical Research Source, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • Lynn Health Science Institute
      • Oklahoma City, Oklahoma, United States, 73103
        • Health Research of Oklahoma, PLLC
    • Pennsylvania
      • Duncansville, Pennsylvania, United States, 16635
        • Altoona Center for Clinical Research, P.C.
    • South Carolina
      • Summerville, South Carolina, United States, 29486
        • Low Country Rheumatology, PA
    • Texas
      • Amarillo, Texas, United States, 79124
        • Amarillo Center for Clinical Research
      • Austin, Texas, United States, 78731
        • Austin Regional Clinic, P.A.
      • Baytown, Texas, United States, 77521
        • Accurate Clinical Management LLC
      • Beaumont, Texas, United States, 77702
        • Pioneer Research Solutions, Inc.
      • Grapevine, Texas, United States, 76034
        • Precision Comprehensive Clinical Research Solutions
      • Houston, Texas, United States, 77065
        • Rheumatology Clinic of Houston, P.A.
      • Houston, Texas, United States, 77089
        • Accurate Clinical Research, Inc.
      • Houston, Texas, United States, 77089
        • Accurate Clinical Mangemnt LLC
      • Houston, Texas, United States, 77382
        • Advanced Rheumatology of Houston
      • Houston, Texas, United States, 77084
        • Accurate Clinical Research
      • League City, Texas, United States, 77573
        • Accurate Clinical Research, Inc.
      • Lubbock, Texas, United States, 79410
        • Endocrinology, Internal Medicine
      • San Antonio, Texas, United States, 78229
        • Dr. Alex De Jesus Rheumatology, P.A.
      • Tomball, Texas, United States, 77375
        • DM Clinical Research
    • Washington
      • Spokane, Washington, United States, 99204
        • Arthritis Northwest, PLLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: Olokizumab q4w
Olokizumab 64 mg subcutaneous q4w +placebo+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular) in order to maintain the blind, subjects randomized to receive OKZ q4w received placebo injections at the alternate q4w interval (e.g., Week 2, Week 6, etc.)
Drug: 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
Drug: Olokizumab 64mg q4w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
Experimental: Arm 2: Olokizumab q2w

Olokizumab 64mg subcutaneous q2w + Methotrexate

64 mg Olokizumab administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)
Drug: Olokizumab 64mg q2w
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
Active Comparator: Arm 3: Adalimumab q2w

Adalimumab 40mg q2w subcutaneous + Methotrexate

Subjects were administered adalimumab 40 mg q2w via SC injection as an active comparator+ concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)
Drug: Adalimumab 40mg q2w
0.4 or 0.8 mL prefilled, single-dose syringe
Other Names:
  • Humira
Placebo Comparator: Arm 4: Placebo q2w

Placebo q2w subcutaneous + Methotrexate

Placebo administered subcutaneously once every 2 weeks + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular)
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response
Time Frame: at Week 12

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects Achieving Low Disease Activity
Time Frame: at Week 12
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
Percentage of Subjects Achieving ACR20 Response: Olokizumab Comparison With Adalimumab
Time Frame: at Week 12

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
Percentage of Subjects Achieving Low Disease Activity: Olokizumab Comparison With Adalimumab
Time Frame: at Week 12
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
Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI)
Time Frame: Baseline to Week 12
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
Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response
Time Frame: at Week 24

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
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)
Time Frame: at Week 24
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

R-Pharm International, LLC

Collaborators

Quintiles, Inc.
OCT Clinical Trials

Investigators

  • Study Director: Mikhail Samsonov, R-Pharm

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2016

Primary Completion (Actual)

August 2, 2019

Study Completion (Actual)

November 5, 2019

Study Registration Dates

First Submitted

April 29, 2016

First Submitted That Met QC Criteria

May 2, 2016

First Posted (Estimated)

May 3, 2016

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 19, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL04041023

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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