Rheumatoid ArthritisPhase 3CREDO 4NCT03120949
Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
A Phase 3 study testing Olokizumab 64 mg SC q4w, Olokizumab 64 mg SC q2w and Concomitant treatment in people with Rheumatoid Arthritis, run by R-Pharm International, LLC at 239 sites in 18 countries.
Trial summary
The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Olokizumab 64 mg SC q4w, Olokizumab 64 mg SC q2w and Concomitant treatment
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,106 participants
- Where
- 239 sitesin 18 countries
- Study dates
- 4 Jul 2017to 1 Sep 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects may be enrolled in the study only if they meet all of the following criteria:
- Subject must be willing and able to sign informed consent
- Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
- Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for ≥ 12 additional weeks
- Subjects must be willing to take folic acid or equivalent throughout the study.
Who cannot join
- Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent Adverse events (AEs) or serious adverse events (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement.
- Subject has evidence of active tuberculosis (TB)
- Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study
- Subjects may be enrolled in the OLE study if they fulfill all 3 of the following criteria prior to the first dose of study treatment:
- Active TB is ruled out by a certified TB specialist or pulmonologist who is familiar with diagnosing and treating TB (as acceptable per local practice);
- The subject starts prophylaxis for latent TB infection (LTBI) according to country-specific/Centers for Disease Control and Prevention (CDC) guidelines (treatment with isoniazid for 6 months is not an appropriate prophylactic regime for this study and it should not be used); and
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- The subject is willing to complete the entire course of recommended LTBI therapy.
- Subject has planned surgery during the first 12 weeks of the OLE study
- Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug
- 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.
- Highly effective contraception is defined as:
- Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to the first dose of study treatment in the core study
- In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by documented follow-up hormone level assessment
- Total abstinence if it is the preferred and constant lifestyle of the subject. Thus, periodic abstinence such as ovulation, symptothermal, postovulation, calendar methods, and withdrawal are not acceptable methods of contraception.
- Male sterilization surgery: at least 6 months prior to the first dose of study treatment in the core study (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate). For female subjects, the vasectomized male should be the only partner.
- Placement of established intrauterine device (IUD): IUD copper or IUD with progesterone
- Barrier method (condom and intravaginal spermicide, cervical caps with spermicide, or diaphragm with spermicide) in combination with the following: established oral, injected, or implanted hormone methods of contraception or contraceptive patch.
- Subject is unwilling or unable to follow the procedures outlined in the protocol.
- Other medical or psychiatric conditions, or laboratory abnormalities that may increase the potential risk associated with study participation and administration of the study treatment, or that may affect study results interpretation and, as per Investigator's judgement, make the subject ineligible.
Trial locations and contacts
239 sites in 18 countries.
239 sites in 18 countries
United States71 sites
Lovelace Scientific Resources, Inc.
Albuquerque, New Mexico, 87114
Amarillo Center for Clinical Research
Amarillo, Texas, 79124
Austin Regional Clinic, P.A.
Austin, Texas, 78731
Accurate Clinical Management., LLC
Baytown, Texas, 77521
RASF - Clinical Research Center
Boca Raton, Florida, 33486
Graves Gilbert Clinic
Bowling Green, Kentucky, 42101
New England Research Associates LLC
Bridgeport, Connecticut, 06606
NYU Langone ambulatory care
Brooklyn, New York, 11201
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45242
Precision Comprehensive Clinical Research Solutions
Colleyville, Texas, 76034
Medvin Clinical Research
Covina, California, 91722
Pioneer Research Solutions, Inc.
Cypress, Texas, 77429
STAT Research, Inc.
Dayton, Ohio, 45417
Denver Arthritis Clinic
Denver, Colorado, 80230
Altoona Center for Clinical Research, P.C.
Duncansville, Pennsylvania, 16635
Arthritis & Osteoporosis Associates, PA
Freehold, New Jersey, 07728
Arthritis Center of North Georgia
Gainesville, Georgia, 30501
AA MRC LLC Ahmed Arif Medical Research Center
Grand Blanc, Michigan, 48439
Medication Management, LLC
Greensboro, North Carolina, 27408
Klein and Associates, M.D., P.A.
Hagerstown, Maryland, 21740
C.V Mehta MD Med Corp..
Hemet, California, 92543
Reliable Clinical Research, LLC
Hialeah, Florida, 33012
CHI St. Vincent Hot Springs
Hot Springs, Arkansas, 71913
Therapeutic Concepts Rheumatology,LLC
Houston, Texas, 77004
Rheumatology Clinic of Houston, P.A.
Houston, Texas, 77065
Houston Institute For Clinical Research
Houston, Texas, 77074
Accurate Clinical Mangemnt - Partner
Houston, Texas, 77089
Accurate Clinical Research, Inc.
Houston, Texas, 77089
Institute of Arthritis Research
Idaho Falls, Idaho, 83404
Glacier View Research Institute-Rheumatology
Kalispell, Montana, 59901
University of Kansas Hospital
Kansas City, Kansas, 66160
Advanced Medical Research, LLC
La Palma, California, 90623
Accurate Clinical Research, Inc.
League City, Texas, 77573
Cape Fear Arthritis Care
Leland, North Carolina, 28451
Physician Research Collaboration
Lincoln, Nebraska, 68516
Valerius Medical Group
Los Alamitos, California, 90720-5403
West Texas Clinical Research
Lubbock, Texas, 79410
Marietta Rheumatology Associates, PC
Marietta, Georgia, 30060
AZ Arthritis & Rheum' Research
Mesa, Arizona, 85210
Pharmax Research Clinic
Miami, Florida, 33126
Medical Research Center of Miami
Miami, Florida, 33134
Suncoast Research Group, LLC
Miami, Florida, 33135
Trinity Medical Group
Minot, North Dakota, 58701
The Arthritis & Diabetes Clinic, Inc.
Monroe, Louisiana, 71203
Javed Rheumatology Associates
Newark, Delaware, 19713
Health Research of Oklahoma, PLLC
Oklahoma City, Oklahoma, 73103
Lynn Health Science Institute
Oklahoma City, Oklahoma, 73112
Omega Research Consultants
Orlando, Florida, 32810
Arthritis Research of Florida, INC
Palm Harbor, Florida, 34684
Stanford University School of Medicine
Palo Alto, California, 94304
Family Clinical Trials, LLC.
Pembroke Pines, Florida, 33026
Arthritis Group
Philadelphia, Pennsylvania, 19152
Arizona Arthritis & Rheumatology Associates, P.C.
Phoenix, Arizona, 85032
Dr Alex De Jesus Rheumatology, P.A.
San Antonio, Texas, 78229
Rheumatology Center of San Diego
San Diego, California, 92128
East Bay Rheumatology Medical Group, Inc.
San Leandro, California, 94578
Arthritis Northwest, PLLC
Spokane, Washington, 99204
Low Country Rheumatology, PA
Summerville, South Carolina, 29486
Arizona Arthritis & Rheumatology Research, PLLC
Sun City, Arizona, 85351
AdventHealth Medical Group, PA
Tampa, Florida, 33614
Advanced Rheumatology of Houston
The Woodlands, Texas, 77382
Clinical Research Source, Inc.
Toledo, Ohio, 43606
DM Clinical Research
Tomball, Texas, 77375
North MS Medical Clinics, Inc.
Tupelo, Mississippi, 38801
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786
Lovelace Scientific Resources, Inc.
Venice, Florida, 34292
Center for Rheumatology Research, Comprehensive Rheumatology Center
West Hills, California, 91307
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902
Medvin Clinical Research
Whittier, California, 90602
Carolina Arthritis Associates
Wilmington, North Carolina, 28401
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605
Russia34 sites
FSBEI HE "Altai State Medical University of the Ministry of Healthcare of Russian Federation"
Barnaul, Altayskiy Kray, 656038
FSBEI HE "Kazan State Medical University of the Ministry of Health of the Russian Federation" on the base of SAHI "Republican Clinical Hospital of the Ministry of Health of Tatarstan Republic"
Kazan', The Republic of Tatarstan, 420012
SAHI of Kemerovo region "Regional Clinical Hospital for War Veterans"
Kemerovo, Kemerovo Oblast, 650000
Medical Center LLC "Maksimum Zdoroviya"
Kemerovo, Kemerovo Oblast, 650066
Budgetary Healthcare Institution "Kursk Regional Clinical Hospital" of Healthcare Committee of Kursk region
Kursk, Kursk Oblast, 305007
SBHI of Moscow "City Clinical Hospital No.1 n.a. Pirogov" Healthcare Department of Moscow
Moscow, Moscovskaya Oblast, 119049
FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation" University Clinical Hospital No.1
Moscow, Moscovskaya Oblast, 119435
FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"
Moscow, Moscovskaya Oblast, 119991
State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
Moscow, Moscow Oblast, 111539
SBHI of Moscow "City Clinical Hospital #4 of Moscow Healthcare Departament"
Moscow, Moscow Oblast, 115093
FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
Moscow, 115522
FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"
Moscow, 119991
SBHI of Nizhegorodsky Region "State Clinical Hospital #5 of Nizhegorodsky District of Nizhny Novgorod"
Nizhny Novgorod, Nizhny Novgorod Oblast, 603005
SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"
Nizhny Novgorod, Nizhny Novgorod Oblast, 603126
State Autonomous Healthcare Institution of Novosibirsk region "City Polyclinic #1"
Novosibirsk, Novosibirsk Oblast, 630005
LLC "Clinical Diagnostic Center "Ultramed"
Omsk, Omsk Oblast, 644024
Budgetary Healthcare Institution of Omsk Region "Regional Clinical Hospital"
Omsk, Omsk Oblast, 644111
SBHI of the Republic of Karelia "Republican Hospital named after V.A. Baranov"
Petrozavodsk, Republic of Karelia, 185019
FSBEI HE "Rostov State Medical Unversity" of Ministry of Health of the Russian Federation
Rostov-on-Don, Rostov Oblast, 344022
FSBEI HE 'Ryazan State Medical University n.a. I.P.Pavlov" of the Ministry of Health of Russian Federation
Ryazan, Ryazan Oblast, 390026
SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit
Saint Petersburg, Leningradskaya Oblast', 190068
FSBI "National Medical Research Center n.a. V.A.Almazov" of the Ministry of Healthcare of the Russian Federation
Saint Petersburg, 197341
FSBEI HE "Saratov SMU n.a. V.I.Razumovsky of Ministry of Health of Russian Federation"
Saratov, Saratov Oblast, 410012
State Healthcare Institution "Regional Clinical Hospital"
Saratov, Saratov Oblast, 410053
Private Healthcare Institution "Clinical Hospital Russian Railways-Medicine of City Smolensk"
Smolensk, Smolensk Oblast, 214025
FSBEI HE StSMU MOH Russia based on SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"
Stavropol, Stavropol Kray, 355030
State Healthcare Institution of Tula region "Tula Regional Clinical Hospital"
Tula, Tulskaya Oblast, 300053
State Budgetary Healthcare Institution "Republican Clinical Hospital n.a. G.G. Kuvatov"
Ufa, Respublic of Bashkortostan, 450005
State Healthcare Institution "Ulyanovsk Regional Clinical Hospital"
Ulyanovsk, Ulyanovsk Oblast, 432063
SBHI of Vladimir Region "Regional Clinical Hospital", Rheumatology Departament
Vladimir, Vladimirskaya Oblast’, 600023
SBHI "Yaroslavl Regional Clinical Hospital", Rheumatology department
Yaroslavl, Yaroslavl Oblast, 150062
State Autonomous Helthcare Institution of Yaroslavl region "Clinical Hospital of Emergency Care n.a. Solovyev"
Yaroslavl, Yaroslavsakaya Oblast, 150003
State Autonomous Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"
Yekaterinburg, Sverdlovsk Oblast, 620102
FSBEI HE "Ural State Medical University" of Ministry of Health of Russian Federation based on MBI "Central City Clinical Hospital No.6"
Yekaterinburg, Sverdlovsk Oblast, 620149
Czechia19 sites
CCR Brno s.r.o
Brno, 602 00
IMEDICA s.r.o.
Brno, 602 00
Revmatologie s.r.o.
Brno, 638 00
Nemocnice Jihlava p.o.
Jihlava, 586 01
MUDr Gabriela Simkova Ordinace Lekare Specialisty Interna Revmatologie
Kladno, 272 01
CTCenter MaVe s.r.o.
Olomouc, 77900
Vesalion s.r.o.
Ostrava, 70200
ARTROSCAN s.r.o.
Ostrava - Trebovice, 722 00
ARTHROHELP s.r.o.
Pardubice, 530 02
CCR Czech, a.s.
Pardubice, 530 02
CLINTRIAL s.r.o.
Prague, 110 00
Revmatologicky ustav
Prague, 128 00
CCR Prague s.r.o.
Prague, 130 00
MUDR Zuzana URBANOVA Revmatologie
Prague, 140 00
Affidea Praha s.r.o.
Prague, 148 00
Fakultni nemocnice v Motole
Prague, 150 06
MUDR Zuzana URBANOVA Revmatologie
Praha 4 Nusle, 140 00
Medical Plus s.r.o.
Uherské Hradiště, 686 01
PV - MEDICAL, s.r.o.
Zlín, 760 01
Poland19 sites
CERMED
Bialystok, 15-270
ZDROWIE Osteo-Medic
Bialystok, 15-351
Szpital Uniwersytecki nr 2 im.dr J. Biziela
Bydgoszcz, 85-168
MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.
Grodzisk Mazowiecki, 05-825
Polimedica Centrum Badań, Profilaktyki I Leczenia
Kielce, 25-355
CCBR - Lodz - PL
Lodz, 90-368
Centrum Medyczne AMED
Lodz, 91-363
ETYKA Osrodek Badan Klinicznych
Olsztyn, 10-117
Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
Sieradz, 98-200
Clinmed Research
Skierniewice, 96-100
RCMed
Sochaczew, 96-500
KO-MED Centra Kliniczne Staszow
Staszów, 28-200
Samodzielny Publiczny ZOZ Tomaszow Lubelski
Tomaszów Lubelski, 22-600
Nasz lekarz Przychodnie Medyczne
Torun, 87-100
Medycyna Kliniczna
Warsaw, 00-874
Rheuma Medicus Zaklad Opieki Zdrowotnej
Warsaw, 02-118
McM Polimedica
Warsaw, 02-777
KO-MED Centra Kliniczne Zamosc
Zamość, 22-400
Santa Familia Centrum Badan, Profilaktyki i Leczenia
Zgierz, 95-100
Argentina14 sites
Instituto de Investigaciones Clinicas-Mar del Plata
Buenos Aires, B7600FZN
Organizacion Medica de Investigacion (OMI)
Ciudad Autonoma Buenos Aires, C1015ABO
APRILLUS Asistencia e Investigacion
Ciudad Autonoma Buenos Aires, C1046AAQ
Instituto Centenario
Ciudad Autonoma Buenos Aires, C1204AAD
Hospital Privado Centro Medico de Cordoba
Córdoba, 5016
Instituto DAMIC Fundacion Rusculleda
Córdoba, X5003DCE
Centro de Investigaciones Medicas Mar del Plata
Mar del Plata, Buenos Aires, B7600FYK
Instituto Medico CER
Quilmes, Buenos Aires, B1878DVB
Instituto de Investigaciones Clinicas Quilmes
Quilmes, Buenos Aires, B1878GEG
CER San Juan Centro Polivalente de Asistencia e Inv. Clinica
San Juan, 5400
Centro Medico Privado de Reumatologia
San Miguel de Tucumán, Tucumán Province, T4000AXL
Centro de Investigaciones Reumatológicas
San Miguel de Tucumán, T4000BRD
Clinica de Higado y Aparato Digestivo
Santa Fe, S2000CFJ
Sanatorio San Martin
Venado Tuerto, Santa Fe Province, S2600KUE
Brazil14 sites
CETI - Centro de Estudos em Terapias Inovadoras Ltda.
Curitiba, Paraná, 80030-110
HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
Fortaleza, Ceará, 60430-370
CIP - Centro Internacional de Pesquisa
Goiânia, Goiás, 74110-120
Clínica de Neoplasias Litoral Ltda.
Itajaí, Santa Catarina, 88301-215
CMiP - Centro Mineiro de Pesquisa
Juiz de Fora, Minas Gerais, 36010-570
Hospital Bruno Born
Lajeado, Rio Grande do Sul, 95900-010
Clinilive - Clínica do Idoso e Pesquisa Clínica
Maringá, Paraná, 87013-250
LMK Serviços Médicos S/S Ltda
Pôrto Alegre, Rio Grande do Sul, 90480-000
CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.
Rio de Janeiro, 20241-180
Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-650
Centro Multidisciplinar de Estudos Clínicos - CEMEC
São Bernardo do Campo, São Paulo, 09715-090
CPCLIN - Centro de Pesquisas Clínicas Ltda.
São Paulo, 01228-200
Associação de Assistência à Criança Deficiente - AACD
São Paulo, 04032-060
CEDOES - Diagnóstico e Pesquisa
Vitória, Espírito Santo, 29055-450
Bulgaria12 sites
DCC 'Sv. Pantaleymon' OOD
Pleven, 5800
UMHAT Pulmed OOD
Plovdiv, 4000
UMHAT "Kaspela", EOOD
Plovdiv, 4001
MHAT - Ruse, AD
Rousse, 7002
Medizinski Zentar-1-Sevlievo EOOD
Sevlievo, 5400
MHAT - Shumen, AD
Shumen, 9700
NMTH "Tsar Boris III"
Sofia, 1233
MHAT "Lyulin", EAD
Sofia, 1336
Medical Center "Excelsior", OOD
Sofia, 1407
UMHAT "Sv. Ivan Rilski", EAD
Sofia, 1431
MC "Synexus - Sofia", EOOD
Sofia, 1784
MDHAT 'Dr. Stefan Cherkezov', AD
Veliko Tarnovo, 5000
Mexico11 sites
Investigacion y Biomedicina de Chihuahua, S.C.
Chihuahua City, 31000
Clinica de Investigacion en Reumatologia y Obesidad S.C.
Guadalajara, Jalisco, 44650
Centro de Estudios de Investigacion Basica y Clinica SC
Guadalajara, Jalisco, 44690
Clinicos Asociados BOCM S.C.
Mexico City, Mexico City, 3300
Centro de Investigacion Clínica GRAMEL S.C
Mexico City, Mexico City, 3720
Comite Mexicano Para la Prevencion de Osteoporosis AC
Mexico City, Mexico City, 6100
Clinstile, S.A. de C.V.
Mexico City, Mexico City, 6700
Clinical Research Institute S.C.
Mexico City, 54055
Accelerium S. de R.L. de C.V.
Monterrey, Nuevo León, 64000
Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
San Luis Potosí City, 78213
Hungary8 sites
Principal SMO Kft.
Baja, 6500
DRC Gyogyszervizsgalo Kozpont Kft.
Balatonfüred, 8230
Clinexpert Kft.
Budapest, 1033
Obudai Egeszsegugyi Centrum Kft.
Budapest, 1036
Kiskunhalasi Semmelweis Korhaz
Kiskunhalas, 6400
DRC Szekesfehervar
Székesfehérvár, 8000
MAV Korhaz es Rendelointezet
Szolnok, 5000
Vital-Medicina Kft.
Veszprém, 8200
South Korea7 sites
Hallym University Sacred Heart Hospital
Anyang-si, Gyeonggi-do, 431-796
Eulji University Hospital
Daejeon, 35233
Chonnam National University Hospital
Gwangju, 501-757
Jeju National University Hospital
Jeju City, 63241
Severance Hospital, Yonsei University No. 31 Office, Pediatric Oncology Clinic
Seoul, 120-752
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul, 6591
Ajou University Hospital
Suwon, Gyeonggi-do, 443-380
Germany6 sites
Rheumapraxis Dr. med. Reiner Kurthen
Aachen, North Rhine-Westphalia, 52064
Kerckhoff-Klinik gGmbH
Bad Nauheim, Hesse, 61231
Klinische Forschung Berlin-Mitte GmbH
Berlin, 10117
HRF Hamburger Rheuma Forschungszentrum
Hamburg, 20095
SMO.MD GmbH
Magdeburg, Saxony-Anhalt, 39120
Studienambulanz Dr. Wassenberg
Ratingen, North Rhine-Westphalia, 40878
Lithuania6 sites
Alytus Regional S. Kudirkos Hospital, Public Institution
Alytus, 62114
Republican Kaunas Hospital, Public Institution
Kaunas, 45130
Klaipeda University Hospital, Public Institution
Klaipėda, 92288
Siauliai Republican Hospital, Public Institution
Šiauliai, 76231
Center Outpatient Clinic, Public Institution
Vilnius, LT-01117
Vilnius University Hospital Santariskiu Clinics, Public Institution
Vilnius, LT-08661
United Kingdom6 sites
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, RG24 9NA
Whipps Cross University Hospital
London, Greater London, E11 1NR
Royal Free Hospital
London, Greater London, NW3 2QG
Maidstone Hospital
Maidstone, Kent, ME16 9QQ
Arrowe Park Hospital
Metropolitan Borough of Wirral, Merseyside, L49 5PE
Torbay Hospital
Torquay, Devon, TQ2 7AA
Colombia5 sites
Centro de Reumatologia y Ortopedia SAS
Barranquilla, 80020
Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
Bogotá, 110221
Fundacion Instituto de Reumatologia Fernando Chalem
Bogotá, 111211
Medicity S.A.S.
Bucaramanga, 680003
Clinica de Artritis Temprana S.A.S
Cali, 76001
Belarus2 sites
Minsk City Clinical Hospital #1
Minsk, Minsk Oblast, 220013
Vitebsk Clinical Hospital
Vitebsk, Vitebsk Oblast, 210037
Estonia2 sites
East Tallinn Central Hospital
Tallinn, 11312
Meditrials OU
Tartu, 50708
Taiwan2 sites
Chi Mei Medical Center, Yung Kang Branch
Tainan, 710
Chang Gung Memorial Hospital, Linkou
Taoyuan, 333
About this study
Official title: A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3 (core studies). The long-term efficacy, immunogenicity, the physical function and quality of life of subjects received long-term treatment with OKZ were assessed as well.
Read the detailed description
This OLE study (CL04041024) included an 82-week open-label Treatment Period that followed completion of one of the core studies (Study CREDO 1, 2 or 3). The OLE open-label Treatment Period lasted from Visit 1 (OLE Baseline/Week 24) to Visit 10 (End of Treatment (EoT)/Week 106), followed by a 20-week Safety Follow-Up Period from Week 106 to Week 126. The first visit of the OLE study was the same visit as the Week 24 visit in the core studies.
Subjects were randomized to 1 of the 2 OKZ treatment groups in the OLE study based on the treatment received in the core studies. Subjects who had received OKZ (q2w or q4w) in the core study in which they had participated (including subjects who received placebo in Study CREDO 3 and were re-randomized to OKZ at Week 16) received the same OKZ treatment regimen in the OLE study. Subjects who had received placebo (Study CREDO 1 and CREDO 2) or adalimumab (Study CREDO 2) in the core study in which they had participated were randomized in a 1:1 ratio to OKZ 64 mg q2w or OKZ 64 mg q4w regimens in the OLE study.
For the first 12 weeks of the OLE, all subjects were required to remain on a stable dose of background methotrexate (MTX) at 15 to 25 mg/week (or≥10 mg/week if there was documented intolerance to higher doses) with a stable route of administration (oral, SC, or intramuscular (IM)). After 12 weeks (Visit 4 [Week 36] of the OLE study), the Investigator might adjust the MTX dosage and route, per local guidelines. Methotrexate might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Subjects who had been on rescue disease-modifying anti-rheumatic drugs (DMARDs) during the core studies were asked to continue these medications for the first 12 weeks of the OLE study. The Investigator could adjust these background medications if deemed appropriate after Visit 4 (Week 36) of the OLE study. Background rescue therapy might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Throughout the study, concomitant treatment with folic acid ≥ 5 mg per week or equivalent was required for all subjects.
Subjects returned to the study site periodically for safety and response assessments as per the Schedule of Events.
The last dose of open-label study treatment in the OLE study was administered at Week 104 for all subjects. After completion of the 82-week open-label Treatment Period, subjects entered the 20-week Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for 3 visits at +4, +8, and +22 weeks after the last dose of study treatment.
Subjects who discontinued the open-label treatment prematurely required to come for the EoT Visit 2 weeks after the last study treatment administration and then return for the 3 Safety Follow-Up Visits +4, +8, and +22 weeks after the last study treatment administration.
Adverse events were assessed throughout the study period and evaluated using the Common Technology Criteria version 4.0 (CTCAE v 4.0).
There were ongoing monitoring of safety events, including laboratory findings by the Sponsor or its designee. In addition, safety parameters were assessed throughout the study by an independent Data Safety Monitoring Board (DSMB).
- Conditions
- Rheumatoid Arthritis
- Being tested
- Olokizumab 64 mg SC q4w, Olokizumab 64 mg SC q2w, Concomitant treatment
- Keywords
- Rheumatoid Arthritis, moderate, severe, subcutaneous, Olokizumab, open-label
- Medical subject headings
- Arthritis, Rheumatoid, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olokizumab 64 mg SC q4wDrug
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS).PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.
Olokizumab 64 mg SC q2wDrug
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.
Concomitant treatmentDrug
Methotrexate 15 to 25 mg/week (or ≥ 10 mg/week if there was documented intolerance to higher doses). (Subject maintained their stable dose and route (oral, SC, or IM) during the core study and for ≥ 12 additional weeks of OLE.)
Folic acid ≥ 5 mg per week or equivalent
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Experimental | Olokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). Receives: Drug: Olokizumab 64 mg SC q4w; Drug: Concomitant treatment |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Experimental | Olokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). Receives: Drug: Olokizumab 64 mg SC q2w; Drug: Concomitant treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population)
Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term
Measured: up to Week 126
Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population)
Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term.
Deaths are included.
Measured: up to Week 126
Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)
Measured: up to Week 126
Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment
Measured: up to Week 126
Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure
Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Measured: up to Week 126
Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure
Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Measured: up to Week 126
Incidence Rate of Treatment Emergent AESIs (Safety Population)
Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Measured: up to Week 126
Secondary outcomes (14)
American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR20 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82.
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)
Measured: up to Week 82
American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR50 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82
American College of Rheumatology 50 % response is a composite defined as a ≥ 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)
Measured: up to Week 82
American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82
Number and Proportion of subjects achieving an ACR70 response who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82
American College of Rheumatology 70 % response is a composite defined as a ≥ 70% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥ 70% 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)
Measured: up to Week 82
Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82
The number and proportion of subjects with SDAI score ≤ 3.3 (considered to be in remission).
The SDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), CRP (mg/dL), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS) + CRP (mg/dL)
Measured: up to week 82
Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82
Number and Proportion of subjects with DAS28 low disease activity (based on DAS28 C-reactive protein (CRP) < 3.2), who remain on randomized open-label treatment and in the study, assessed at several timepoints up to Week 82.
The DAS28 (CRP) was calculated in the statistical database for analysis purposes using the Swollen joint count (SJC) (28 joints), Tender joint count (TJC) (28 joints), CRP level, and the Patient Global Assessment of Disease Activity Visual Analog Scale (VAS) (100 mm VAS, where 0 is "no disease activity" and 100 was "maximal disease activity") according to the following formula: [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.36 × natural log (CRP+1)] + [0.014 × VAS] + 0.96.
Measured: up to Week 82
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 12
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 20
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 28
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 40
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 52
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 64
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: Core baseline, Week 82
Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82
The number and proportion of subjects with HAQ-DI improvement ≥ 0.22 Against OLE Baseline.
HAQ-DI Range: 0 (the best outcome) - 3 (the worst outcome), with a decrease from baseline indicating improvement.
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 (activity) 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 (i.e., question in each category with the highest score for that category). The HAQ-DI was calculated by dividing the sum of the category scores by the number of categories with at least 1 question answered.
Measured: up to week 82
Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI)
CDAI Range: 0 (the best outcome) - 76 (the worst outcome), with a decrease from baseline indicating improvement.
The CDAI was calculated in the statistical database for analysis purposes using the SJC (28 joints), TJC (28 joints), the Patient Global Assessment of Disease Activity (VAS) (in cm), and the Physician Global Assessment (VAS) (in cm) according to the following formula: CDAI = SJC + TJC + Patient Global Assessment of Disease Activity (VAS) + Physician Global Assessment (VAS)
Measured: up to week 82
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2017
- Study start4 Jul 2017
- Primary completion1 Sep 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,106 participants (actual)
Sponsor and investigators
- Lead sponsor
- R-Pharm International, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pvt. Ltd, OCT Clinical Trials
- Responsible party
- Sponsor
- Investigators
- Mikhail Samsonov, Study director, Chief Medical Officer, R-Pharm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03120949
- Sponsor's protocol ID
- CL04041024
- Other IDs
- 2015-005309-35, 2015
- Acronym
- CREDO 4
- Status last verified
- Sep 2023
- First submitted
- 7 Feb 2017
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Fleischmann RM, Strand V, Feist E, Lisitsyna T, Sparks JA, Nasonov E, Samsonov M, Grishin S, Egorova A, Kuzkina S, Smolen JS. Olokizumab Improves Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis up to 106 Weeks (Results from the Open-Label Extension of Phase III Randomized Clinical Trials). Rheumatol Ther. 2026 Aug;13(4):1055-1074. doi: 10.1007/s40744-026-00852-3. Epub 2026 May 16.
PubMed 42142212
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03120949
- Acronym / sponsor ID
- CREDO 4 / CL04041024
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, moderate, severe, subcutaneous, Olokizumab, open-label
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,106 participants (actual)
- Lead sponsor
- R-Pharm International, LLCIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pvt. Ltd, OCT Clinical Trials
- Study start
- 4 Jul 2017 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 19 Apr 2017 (actual)
- Results
- Posted 7 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study was to evaluate the long-term safety and tolerability of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA) who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3 (core studies). The long-term efficacy, immunogenicity, the physical function and quality of life of subjects received long-term treatment with OKZ were assessed as well.
Detailed description
This OLE study (CL04041024) included an 82-week open-label Treatment Period that followed completion of one of the core studies (Study CREDO 1, 2 or 3). The OLE open-label Treatment Period lasted from Visit 1 (OLE Baseline/Week 24) to Visit 10 (End of Treatment (EoT)/Week 106), followed by a 20-week Safety Follow-Up Period from Week 106 to Week 126. The first visit of the OLE study was the same visit as the Week 24 visit in the core studies.
Subjects were randomized to 1 of the 2 OKZ treatment groups in the OLE study based on the treatment received in the core studies. Subjects who had received OKZ (q2w or q4w) in the core study in which they had participated (including subjects who received placebo in Study CREDO 3 and were re-randomized to OKZ at Week 16) received the same OKZ treatment regimen in the OLE study. Subjects who had received placebo (Study CREDO 1 and CREDO 2) or adalimumab (Study CREDO 2) in the core study in which they had participated were randomized in a 1:1 ratio to OKZ 64 mg q2w or OKZ 64 mg q4w regimens in the OLE study.
For the first 12 weeks of the OLE, all subjects were required to remain on a stable dose of background methotrexate (MTX) at 15 to 25 mg/week (or≥10 mg/week if there was documented intolerance to higher doses) with a stable route of administration (oral, SC, or intramuscular (IM)). After 12 weeks (Visit 4 [Week 36] of the OLE study), the Investigator might adjust the MTX dosage and route, per local guidelines. Methotrexate might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Subjects who had been on rescue disease-modifying anti-rheumatic drugs (DMARDs) during the core studies were asked to continue these medications for the first 12 weeks of the OLE study. The Investigator could adjust these background medications if deemed appropriate after Visit 4 (Week 36) of the OLE study. Background rescue therapy might be adjusted only for safety reasons according to Investigator discretion before Visit 4 (Week 36) of the OLE study.
Throughout the study, concomitant treatment with folic acid ≥ 5 mg per week or equivalent was required for all subjects.
Subjects returned to the study site periodically for safety and response assessments as per the Schedule of Events.
The last dose of open-label study treatment in the OLE study was administered at Week 104 for all subjects. After completion of the 82-week open-label Treatment Period, subjects entered the 20-week Safety Follow-Up Period. During the Safety Follow-Up Period, subjects returned for 3 visits at +4, +8, and +22 weeks after the last dose of study treatment.
Subjects who discontinued the open-label treatment prematurely required to come for the EoT Visit 2 weeks after the last study treatment administration and then return for the 3 Safety Follow-Up Visits +4, +8, and +22 weeks after the last study treatment administration.
Adverse events were assessed throughout the study period and evaluated using the Common Technology Criteria version 4.0 (CTCAE v 4.0).
There were ongoing monitoring of safety events, including laboratory findings by the Sponsor or its designee. In addition, safety parameters were assessed throughout the study by an independent Data Safety Monitoring Board (DSMB).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm 1: OKZ 64 mg q4w + MTX | Experimental | Drug: Olokizumab 64 mg SC q4w, Drug: Concomitant treatmentOlokizumab 64 mg SC q4w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). |
| Treatment Arm 2: OKZ 64 mg q2w + MTX | Experimental | Drug: Olokizumab 64 mg SC q2w, Drug: Concomitant treatmentOlokizumab 64 mg SC q2w + concomitant background therapy (Methotrexate) at a stable dose with a stable route of administration (oral, subcutaneous, or intramuscular). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject must be willing and able to sign informed consent
- Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).
- Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study and plan to maintain the same dose and route of administration for ≥ 12 additional weeks
- Subjects must be willing to take folic acid or equivalent throughout the study.
Key exclusion criteria (19 listed)
- Subject with any medically important condition in the core study (e.g., clinically significant laboratory values, frequent Adverse events (AEs) or serious adverse events (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical condition) which would make this subject unsuitable for inclusion in the open-label extension (OLE) study in the Investigator's judgement.
- Subject has evidence of active tuberculosis (TB)
- Subject with a positive or repeated indeterminate interferon-gamma release assay (IGRA) result at Week 22 of the core study
- Subject has planned surgery during the first 12 weeks of the OLE study
- Female subjects who are pregnant or who are planning to become pregnant during the study or within 6 months of the last dose of study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olokizumab 64 mg SC q4w160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS).PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL. | Drug | Treatment Arm 1: OKZ 64 mg q4w + MTX |
| Olokizumab 64 mg SC q2w160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL. | Drug | Treatment Arm 2: OKZ 64 mg q2w + MTX |
| Concomitant treatmentMethotrexate 15 to 25 mg/week (or ≥ 10 mg/week if there was documented intolerance to higher doses). (Subject maintained their stable dose and route (oral, SC, or IM) during the core study and for ≥ 12 additional weeks of OLE.) Folic acid ≥ 5 mg per week or equivalent | Drug | Treatment Arm 1: OKZ 64 mg q4w + MTX, Treatment Arm 2: OKZ 64 mg q2w + MTX |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population)
Time frame: up to Week 126
Incidence of Treatment-Emergent Adverse Events Reported for ≥5% of Subjects in Any Treatment Group by System Organ Class or Preferred Term
Incidence of Treatment-Emergent Serious Adverse Events (SAEs), by System Organ Class and Preferred Term (Safety Population)
Time frame: up to Week 126
Incidence of Serious Treatment-Emergent Adverse Events by System Organ Class or Preferred Term. Deaths are included.
Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)
Time frame: up to Week 126
Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment
Time frame: up to Week 126
Incidence Rate of Treatment Emergent AEs Per Patient-years of Exposure
Time frame: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent AE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence Rate of Treatment Emergent SAEs Per Patient-years of Exposure
Time frame: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent SAE. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
Incidence Rate of Treatment Emergent AESIs (Safety Population)
Time frame: up to Week 126
Incidence Rate of all Subjects with at Least One Treatment Emergent AESI. Subject Incidence Rate (IR) is summarized per 100 subject years (SY) of follow-up (/100 SY) based on the OLE safety population and presented by study treatments.
14 secondary outcomes
American College of Rheumatology 20% (ACR20) Response Rates Compare Against Core Baseline Through Week 82
Time frame: up to Week 82
American College of Rheumatology 50% (ACR50) Response Rates Compare Against Core Baseline Through Week 82
Time frame: up to Week 82
American College of Rheumatology 70% (ACR70) Response Rates Compare Against Core Baseline Through Week 82
Time frame: up to Week 82
Proportion of Subjects With Simplified Disease Activity Index (SDAI) Remission Through Week 82
Time frame: up to week 82
Disease Activity Score 28-joint Count (DAS28) Response Rates Through Week 82
Time frame: up to Week 82
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 12
Time frame: Core baseline, Week 12
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 20
Time frame: Core baseline, Week 20
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 28
Time frame: Core baseline, Week 28
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 40
Time frame: Core baseline, Week 40
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 52
Time frame: Core baseline, Week 52
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 64
Time frame: Core baseline, Week 64
Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Core Baseline at Week 82
Time frame: Core baseline, Week 82
Proportion of Subjects With Health Assessment Questionnaire - Disability Index (HAQ-DI) Improvement Through Week 82
Time frame: up to week 82
Changes From Core Baseline Over Time in Clinical Disease Activity Index (CDAI)
Time frame: up to week 82
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42142212Fleischmann RM, Strand V, Feist E, Lisitsyna T, Sparks JA, Nasonov E, Samsonov M, Grishin S, Egorova A, Kuzkina S, Smolen JS. Olokizumab Improves Patient-Reported Outcomes in Patients with Active Rheumatoid Arthritis up to 106 Weeks (Results from the Open-Label Extension of Phase III Randomized Clinical Trials). Rheumatol Ther. 2026 Aug;13(4):1055-1074. doi: 10.1007/s40744-026-00852-3. Epub 2026 May 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikhail Samsonov study director
Chief Medical Officer, R-Pharm
239 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Olokizumab 64 mg SC q4w, Olokizumab 64 mg SC q2w and Concomitant treatment in people with Rheumatoid Arthritis, run by R-Pharm International, LLC at 239 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 239 sites in United States, Russia, Czechia, Poland, Argentina and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (AEs), by System Organ Class and Preferred Term (Safety Population) (time frame: up to Week 126). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03120949, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.