Evaluation of the Efficacy and Safety of Two Dosing Regimens of Olokizumab (OKZ), Compared to Placebo, in Subjects With Rheumatoid Arthritis (RA) Who Were Taking an Existing Medication Called a Tumour Necrosis Factor Alpha Inhibitor But Had Active Disease
CREDO 3
A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy
2 other identifiers
interventional
368
11 countries
116
Brief Summary
The purpose of this study was to determine how effective and safe the study drug Olokizumab was in patients with Rheumatoid Arthritis (RA) who had been already receiving, but not fully responding to treatment with an existing medication called a tumour necrosis factor alpha inhibitor The primary objective of this study was to evaluate the efficacy of olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once every 4 weeks (q4w) relative to placebo in subjects with moderately to severely active rheumatoid arthritis (RA) inadequately controlled by TNF-α inhibitor (TNFi) therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 rheumatoid-arthritis
Started Jan 2017
Typical duration for phase_3 rheumatoid-arthritis
116 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 29, 2016
CompletedFirst Posted
Study publicly available on registry
May 3, 2016
CompletedStudy Start
First participant enrolled
January 25, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 12, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2019
CompletedResults Posted
Study results publicly available
July 21, 2021
CompletedSeptember 21, 2023
September 1, 2023
2.6 years
April 29, 2016
January 26, 2021
September 19, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response
The difference between OKZ and placebo in the percentage of subjects achieving an ACR20 response and remaining on randomized treatment and in the study at Week 12. A responder is defined as any subject satisfying ACR20 criteria and remaining on randomized treatment and in the study at Week 12. American College of Rheumatology 20 % response is a composite defined as a ≥ 20% improvement from baseline in the swollen joint counts assessed in 66 joints and in the tender joint count assessed in 68 joints; and a ≥20% improvement from baseline in at least 3 of the 5 remaining core set measures: * Patient Global Assessment of Disease Activity (VAS) * Patient Assessment of Pain (VAS) * HAQ-DI * Physician Global Assessment (VAS) * Level of acute phase reactant (CRP)
at Week 12
Secondary Outcomes (4)
Percentage of Subjects Achieving Low Disease Activity
at Week 12
Improvement of Physical Ability From Baseline to Week 12, as Measured by the Health Assessment Questionnaire Disability Index (HAQ-DI)
Baseline to Week 12
Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response
at Week 12
Percentage of Subjects With Clinical Disease Activity Index (CDAI) ≤ 2.8 (Remission)
at Week 12
Study Arms (3)
Arm 1: Olokizumab q4w
EXPERIMENTALOlokizumab 64mg subcutaneous q4w + placebo + Methotrexate 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.)
Arm 2: Olokizumab q2w
EXPERIMENTALOlokizumab 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)
Arm 3: Placebo q2w
PLACEBO COMPARATORPlacebo 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) Starting at Week 16, all subjects in the placebo group were randomized in a blinded fashion to receive either OKZ 64 mg q2w or OKZ 64 mg q4w; equal numbers of subjects were planned to be assigned to each OKZ treatment group.
Interventions
160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial
sodium chloride 0.9% solution provided as either a 10 mL vial or ampoule, depending on market availability. Each placebo will be packed into a cardboard carton to contain 1 vial or ampoule
Eligibility Criteria
You may qualify if:
- Subjects may be enrolled in the study only if they meet all of the following criteria.
- Subjects willing and able to sign informed consent
- Subjects must have a diagnosis of adult onset RA classified by ACR/EULAR 2010 revised classification criteria for RA for at least 24 weeks prior to Screening.
- (If the subject was diagnosed according to ACR 1987 criteria previously, the Investigator may classify the subject per ACR 2010 retrospectively, using available source data.)
- Treatment with oral, SC, or intramuscular (IM) MTX for at least 12 weeks prior to Screening at a dose of 15 to 25 mg/week (or ≥10 mg/week if there is documented intolerance to higher doses)
- The dose and means of administering MTX must have been stable for at least 6 weeks prior to Screening.
- Subjects must be willing to take folic acid or equivalent throughout the study.
- Subjects must have moderately to severely active RA disease as defined by all of the following:
- ≥6 tender joints (68 joint count) at Screening and baseline; and
- ≥6 swollen joints (66 joint count) at Screening and baseline; and
- C-reactive protein (CRP) above Upper limit of normal (ULN) at Screening based on the central laboratory results.
- Subjects must have a documented inadequate response to treatment (i.e., TNFi failure) with ≥1 licensed TNFi following at least 12 weeks of therapy with that agent. Inadequate response to treatment is classified as either:
- Primary failure: The absence of any documented clinically significant response; or
- Secondary failure: Documented initial response with subsequent loss of that response or partial response
You may not qualify if:
- Diagnosis of any other inflammatory arthritis or systemic rheumatic disease (e.g., gout, psoriatic or reactive arthritis, Crohn's disease, Lyme disease, juvenile idiopathic arthritis, or systemic lupus erythematosus) (However, subjects may have secondary Sjogren's syndrome or hypothyroidism.)
- Subjects who are Steinbrocker class IV functional capacity (incapacitated, largely or wholly bed-ridden or confined to a wheelchair, with little or no self-care)
- Prior exposure to any licensed or investigational compound directly or indirectly targeting Interleukin (IL) 6 or IL 6R (including tofacitinib or other Janus kinases and spleen tyrosine kinase \[SYK\] inhibitors)
- Prior treatment with cell depleting therapies including anti CD20 or investigational agents (e.g., CAMPATH, anti CD4, anti CD5, anti CD3, and anti CD19) with the exception of rituximab, which is allowed if it was discontinued at least 24 weeks prior to baseline (rituximab should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA).
- Prior use of bDMARDs, within the following windows prior to baseline (bDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):
- weeks for etanercept and anakinra
- weeks for infliximab
- weeks for adalimumab, certolizumab, and golimumab
- weeks for abatacept
- Use of parenteral and/or intra-articular glucocorticoids within 4 weeks prior to baseline
- Use of oral glucocorticoids greater than 10 mg/day prednisone (or equivalent) or change in dosage within 2 weeks prior to baseline
- Prior documented history of no response to hydroxychloroquine and sulfasalazine
- Prior use of cDMARDs (other than MTX) within the following windows prior to baseline (cDMARDs should not be discontinued to facilitate a subject's participation in the study, but should instead have been previously discontinued as part of a subject's medical management of RA):
- weeks for sulfasalazine, azathioprine, cyclosporine, hydroxychloroquine, chloroquine, gold, penicillamine, minocycline, or doxycycline
- 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
- +27 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- R-Pharm International, LLClead
- Quintiles, Inc.collaborator
- OCT Clinical Trialscollaborator
- Mene Researchcollaborator
Study Sites (116)
Arizona Arthritis & Rheumatology Associates, P.C.
Phoenix, Arizona, 85032, United States
CHI St. Vincent Hot Springs
Hot Springs, Arkansas, 71913, United States
Medvin Clinical Research
Covina, California, 91722, United States
TriWest Research Associates, LLC
El Cajon, California, 92020-4124, United States
Saint Jude Heritage Medical Grp
Fullerton, California, 92835, United States
С V Mehta MD Med Corp.
Hemet, California, 92543, United States
Advanced Medical Research, LLC
Lakewood, California, 90623, United States
Stanford University School of Medicine
Palo Alto, California, 94304, United States
Riverside Medical Clinic
Riverside, California, 92506, United States
East Bay Rheumatology Medical Group, Inc.
San Leandro, California, 94578, United States
Inland Rheumatology Clinical Trials, Inc.
Upland, California, 91786, United States
Denver Arthritis Clinic
Denver, Colorado, 80230, United States
Javed Rheumatology Associates
Newark, Delaware, 19713, United States
RASF - Clinical Research Center
Boca Raton, Florida, 33486, United States
Suncoast Research Group LLC
Miami, Florida, 33135, United States
Omega Research Consultants
Orlando, Florida, 32810, United States
Family Clinical Trials, LLC.
Pembroke Pines, Florida, 33026, United States
AdventHealth Medical Group, PA
Tampa, Florida, 33614, United States
Institute of Arthritis Research
Idaho Falls, Idaho, 83404, United States
University of Kansas Hospital
Kansas City, Kansas, 66160, United States
Graves Gilbert Clinic
Bowling Green, Kentucky, 42101, United States
The Arthritis & Diabetes Clinic, Inc.
Monroe, Louisiana, 71203, United States
Klein and Associates, M.D., P.A.
Hagerstown, Maryland, 21740, United States
The Center for Rheumatology and Bone Research
Wheaton, Maryland, 20902, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605, United States
Glacier View Research Instutute-Rheumatology
Kalispell, Montana, 59901, United States
Arthritis & Osteoporosis Associates, PA
Freehold, New Jersey, 07728, United States
Lovelace Scientific Resources, Inc.
Albuquerque, New Mexico, 87114, United States
NYU Langone Ambulatory Care
New York, New York, 11201, United States
Medication Management, LLC
Greensboro, North Carolina, 27408, United States
Cape Fear Arthritis Care
Leland, North Carolina, 28451, United States
Carolina Arthritis Associates
Wilmington, North Carolina, 28401, United States
Trinity Medical Group
Minot, North Dakota, 58701, United States
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45242, United States
STAT Research, Inc.
Dayton, Ohio, 45417, United States
Clinical Research Source, Inc.
Perrysburg, Ohio, 43606, United States
Arthritis Group
Philadelphia, Pennsylvania, 19152, United States
Low Country Research Center
Charleston, South Carolina, 29486, United States
Amarillo Center for Clinical Research
Amarillo, Texas, 79124, United States
Austin Regional Clinic, P.A.
Austin, Texas, 78731, United States
Accurate Clinical Research, Inc.
Baytown, Texas, 77521, United States
Precision Comprehensive Clinical Research Solutions
Grapevine, Texas, 76034, United States
Therapeutic Concepts Rheumatology, LLC
Houston, Texas, 77004, United States
Rheumatology Clinic of Houston, P.A.
Houston, Texas, 77065, United States
Accurate Clinical Research, Inc.
Houston, Texas, 77089, United States
Pioneer Research Solutions, Inc.
Houston, Texas, 77429, United States
Accurate Clinical Research, Inc.
League City, Texas, 77573, United States
Endocrinology, Internal Medicine
Lubbock, Texas, 79410, United States
Dr. Alex De Jesus Rheumatology, P.A.
San Antonio, Texas, 78229, United States
Advanced Rheumatology of Houston
Woodville, Texas, 77382, United States
Centro de Investigaciones Medicas Mar del Plata
Mar del Plata, Buenos Aires, B7600FYK, Argentina
Instituto de Investigaciones Clinicas
Mar del Plata, Buenos Aires, B7600FZN, Argentina
Instituto de Investigaciones Clinicas Quilmes
Quilmes, Buenos Aires, B1878GEG, Argentina
Clinica de Higado y Aparato Digestivo
Rosario, Santa Fe Province, S2000CFJ, Argentina
Sanatorio San Martin
Venado Tuerto, Santa Fe Province, S2600KUE, Argentina
Centro Medico Privado de Reumatologia
San Miguel de Tucumán, Tucumán Province, T4000AXL, Argentina
Centro de Investigaciones Reumatológicas
San Miguel de Tucumán, Tucumán Province, T4000BRD, Argentina
Atencion Integral en Reumatologia (AIR)
Ciudad Autonoma Buenos Aires, 1426, Argentina
Organizacion Medica de Investigacion (OMI)
Ciudad Autonoma Buenos Aires, C1015ABO, Argentina
APRILLUS
Ciudad Autonoma Buenos Aires, C1046AAQ, Argentina
Instituto Centenario
Ciudad Autonoma Buenos Aires, C1204AAD, Argentina
Hospital Privado Centro Medico de Cordoba S.A
Córdoba, 5016, Argentina
Centro Polivalente de Asistencia e Inv. Clinica CER
San Juan, 5400, Argentina
HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
Fortaleza, Ceará, 60430-370, Brazil
CEDOES - Diagnóstico e Pesquisa
Vitória, Espírito Santo, 29055450, Brazil
CIP - Centro Internacional de Pesquisa
Goiânia, Goiás, 74110-120, Brazil
CMiP - Centro Mineiro de Pesquisa
Juiz de Fora, Minas Gerais, 36010-570, Brazil
CETI - Centro de Estudos em Terapias Inovadoras Ltda.
Curitiba, Paraná, 80030-110, Brazil
Hospital Bruno Born
Lajeado, Rio Grande do Sul, 95900-010, Brazil
LMK Serviços Médicos S/S Ltda
Porto Alegre, Rio Grande do Sul, 90480-000, Brazil
Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-650, Brazil
Centro Multidisciplinar de Estudos Clínicos - CEMEC
São Bernardo do Campo, São Paulo, 09715-090, Brazil
Clínica de Neoplasias Litoral Ltda.
Santa Catarina, 88301-215, Brazil
CPCLIN - Centro de Pesquisas Clínicas Ltda.
São Paulo, 01228-200, Brazil
Associação de Assistência à Criança Deficiente - AACD
São Paulo, 04032-060, Brazil
Centro de Reumatologia y Ortopedia SAS
Barranquilla, 80020, Colombia
Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM
Bogotá, 110221, Colombia
Medicity S.A.S.
Bucaramanga, 680003, Colombia
Clinica de Artritis Temprana S.A.
Cali, 76001, Colombia
Revmatologie MUDr. Klara Sirova s.r.o.
Ostrava - Moravska Ostrava, 70200, Czechia
CCR Czech, a.s.
Pardubice, 53002, Czechia
MEDICAL PLUS s.r.o.
Uherské Hradiště, 68601, Czechia
PV - Medical, s.r.o.
Zlín, 760 01, Czechia
Kerckhoff-Klinik gGmbH
Bad Nauheim, Hesse, 61231, Germany
SMO.MD GmbH
Magdeburg, Saxony-Anhalt, 39120, Germany
HRF Hamburger Rheuma Forschungszentrum
Hamburg, 20095, Germany
Clinexpert Egeszsegugyi Szolg. es Ker. Kft.
Budapest, 1033, Hungary
Obudai Egeszsegugyi Centrum
Budapest, 1036, Hungary
MAV Korhaz és Rendelointezet
Szolnok, 5000, Hungary
Vital Medical Center
Veszprém, 8200, Hungary
Clinica de Investigacion en Reumatologia y Obesidad S.C.
Guadalajara, Jalisco, 44650, Mexico
Centro de Estudios de Investigacion Basica y Clinica SC
Guadalajara, Jalisco, 44690, Mexico
Centro de Investigacion Clínica GRAMEL S.C
Mexico City, Mexico City, 03720, Mexico
Clinstile, S.A. de C.V.
Mexico City, Mexico City, 06700, Mexico
Accelerium S. de R.L. de C.V.
Monterrey, Nuevo León, 64000, Mexico
Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez
Monterrey, Nuevo León, 64460, Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
San Luis Potosí City, San Luis Potos, 78213, Mexico
Investigacion y Biomedicina de Chihuahua, S.C.
Chihuahua City, 31000, Mexico
Szpital Uniwersytecki nr 2 im.dr J. Biziela
Bydgoszcz, 85-168, Poland
McBk S.C.
Grodzisk Mazowiecki, 05-825, Poland
Centrum Medyczne AMED
Lodz, 91-363, Poland
Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego
Sieradz, 98-200, Poland
Samodzielny Publiczny ZOZ Tomaszow Lubelski
Tomaszów Lubelski, 22-600, Poland
McM Polimedica
Warsaw, 02-777, Poland
State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department
Moscow, Moscow Oblast, 111539, Russia
City Clinical Hospital #1
Novosibirsk, Novosibirsk Oblast, 630099, Russia
Diagnostic Center Ultramed
Omsk, Omsk Oblast, 644024, Russia
SBHI of the Republic of Karelia "Republican Hospital named after V.A.Baranov"
Petrozavodsk, Republic of Karelia, 185019, Russia
Rostov State Medical Unversity
Rostov-on-Don, Rostov Oblast, 344022, Russia
SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"
Stavropol, Stavropol Kray, 355030, Russia
Regional Clinical Hospital
Vladimir, Vladimirskaya Oblast’, 600023, Russia
FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"
Moscow, 115522, Russia
Ajou University Hospital
Suwon, Gyeonggi-do, 443-380, South Korea
Chonnam National University Hospital
Gwangju, 61469, South Korea
Hallym University Sacred Heart Hospital
Gyeonggi-do, 431-796, South Korea
Severance Hospital, Yonsei University
Seoul, 3722, South Korea
Related Publications (1)
Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
PMID: 36109142DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Maria Lemak, Scientific Advisor
- Organization
- R-Pharm
Study Officials
- STUDY DIRECTOR
Mikhail Samsonov
R-Pharm
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 29, 2016
First Posted
May 3, 2016
Study Start
January 25, 2017
Primary Completion
September 12, 2019
Study Completion
October 1, 2019
Last Updated
September 21, 2023
Results First Posted
July 21, 2021
Record last verified: 2023-09