Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— CREDO 4  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03120949
• Other study ID #: CL04041024
• Secondary ID: 2015-005309-35
• Status: Completed
• Phase: Phase 3
• Start date: July 4, 2017
• Est. completion date: September 1, 2021

Study information

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

Clinical 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 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2106
• Est. completion date: September 1, 2021
• Est. primary completion date: September 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

1. Subject must be willing and able to sign informed consent

2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3 core studies (CL04041022, CL04041023, or CL04041025).

3. 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

4. Subjects must be willing to take folic acid or equivalent throughout the study.

Exclusion Criteria:

1. 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.

2. Subject has evidence of active tuberculosis (TB)

3. 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:

1. 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);

2. 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

3. The subject is willing to complete the entire course of recommended LTBI therapy.

4. Subject has planned surgery during the first 12 weeks of the OLE study

5. 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

6. 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.

7. Subject is unwilling or unable to follow the procedures outlined in the protocol.

8. 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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Olokizumab 64 mg SC q4w
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 q2w
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 treatment
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

Locations

Country	Name	City	State
Argentina	Instituto de Investigaciones Clinicas-Mar del Plata	Buenos Aires
Argentina	APRILLUS Asistencia e Investigacion	Ciudad Autonoma Buenos aires
Argentina	Instituto Centenario	Ciudad Autonoma Buenos Aires
Argentina	Organizacion Medica de Investigacion (OMI)	Ciudad Autonoma Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Instituto DAMIC Fundacion Rusculleda	Córdoba
Argentina	Centro de Investigaciones Medicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes	Buenos Aires
Argentina	Instituto Medico CER	Quilmes	Buenos Aires
Argentina	CER San Juan Centro Polivalente de Asistencia e Inv. Clinica	San Juan
Argentina	Centro Medico Privado de Reumatologia	San Miguel de Tucuman	Tucuman
Argentina	Clinica de Higado y Aparato Digestivo	Santa Fe
Argentina	Centro de Investigaciones Reumatológicas	Tucuman
Argentina	Sanatorio San Martin	Venado Tuerto	Santa Fe
Belarus	Minsk City Clinical Hospital #1	Minsk	Minsk Oblast
Belarus	Vitebsk Clinical Hospital	Vitebsk	Vitebsk Oblast
Brazil	CETI - Centro de Estudos em Terapias Inovadoras Ltda.	Curitiba	Paraná
Brazil	HUWC - UFC - Hospital Universitário Walter Cantídio - Universidade Federal do Ceará	Fortaleza	Ceará
Brazil	CIP - Centro Internacional de Pesquisa	Goiânia	Goiás
Brazil	Clínica de Neoplasias Litoral Ltda.	Itajaí	Santa Catarina
Brazil	CMiP - Centro Mineiro de Pesquisa	Juiz de Fora	Minas Gerais
Brazil	Hospital Bruno Born	Lajeado	Rio Grande Do Sul
Brazil	Clinilive - Clínica do Idoso e Pesquisa Clínica	Maringá	Paraná
Brazil	LMK Serviços Médicos S/S Ltda	Pôrto Alegre	Rio Grande Do Sul
Brazil	CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda.	Rio de Janeiro
Brazil	Faculdade de Medicina do ABC	Santo André	Sao Paulo
Brazil	Centro Multidisciplinar de Estudos Clínicos - CEMEC	Sao Bernardo Do Campo	Sao Paulo
Brazil	Associação de Assistência à Criança Deficiente - AACD	São Paulo
Brazil	CPCLIN - Centro de Pesquisas Clínicas Ltda.	São Paulo
Brazil	CEDOES - Diagnóstico e Pesquisa	Vitória	Espírito Santo
Bulgaria	DCC 'Sv. Pantaleymon' OOD	Pleven
Bulgaria	UMHAT "Kaspela", EOOD	Plovdiv
Bulgaria	UMHAT Pulmed OOD	Plovdiv
Bulgaria	MHAT - Ruse, AD	Ruse
Bulgaria	Medizinski Zentar-1-Sevlievo EOOD	Sevlievo
Bulgaria	MHAT - Shumen, AD	Shumen
Bulgaria	MC "Synexus - Sofia", EOOD	Sofia
Bulgaria	Medical Center "Excelsior", OOD	Sofia
Bulgaria	MHAT "Lyulin", EAD	Sofia
Bulgaria	NMTH "Tsar Boris III"	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD	Sofia
Bulgaria	MDHAT 'Dr. Stefan Cherkezov', AD	Veliko Tarnovo
Colombia	Centro de Reumatologia y Ortopedia SAS	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM	Bogotá
Colombia	Fundacion Instituto de Reumatologia Fernando Chalem	Bogotá
Colombia	Medicity S.A.S.	Bucaramanga
Colombia	Clinica de Artritis Temprana S.A.S	Cali
Czechia	CCR Brno s.r.o	Brno
Czechia	IMEDICA s.r.o.	Brno
Czechia	Revmatologie s.r.o.	Brno
Czechia	Nemocnice Jihlava p.o.	Jihlava
Czechia	MUDr Gabriela Simkova Ordinace Lekare Specialisty Interna Revmatologie	Kladno
Czechia	CTCenter MaVe s.r.o.	Olomouc
Czechia	Vesalion s.r.o.	Ostrava
Czechia	ARTROSCAN s.r.o.	Ostrava - Trebovice
Czechia	ARTHROHELP s.r.o.	Pardubice
Czechia	CCR Czech, a.s.	Pardubice
Czechia	Affidea Praha s.r.o.	Praha
Czechia	CLINTRIAL s.r.o.	Praha
Czechia	Revmatologicky ustav	Praha 2
Czechia	CCR Prague s.r.o.	Praha 3
Czechia	MUDR Zuzana URBANOVA Revmatologie	Praha 4
Czechia	MUDR Zuzana URBANOVA Revmatologie	Praha 4 Nusle
Czechia	Fakultni nemocnice v Motole	Praha 5
Czechia	Medical Plus s.r.o.	Uherske Hradiste
Czechia	PV - MEDICAL, s.r.o.	Zlin
Estonia	East Tallinn Central Hospital	Tallinn
Estonia	Meditrials OU	Tartu
Germany	Rheumapraxis Dr. med. Reiner Kurthen	Aachen	Nordrhein Westfalen
Germany	Kerckhoff-Klinik gGmbH	Bad Nauheim	Hessen
Germany	Klinische Forschung Berlin-Mitte GmbH	Berlin
Germany	HRF Hamburger Rheuma Forschungszentrum	Hamburg
Germany	SMO.MD GmbH	Magdeburg	Sachsen Anhalt
Germany	Studienambulanz Dr. Wassenberg	Ratingen	Nordrhein Westfalen
Hungary	Principal SMO Kft.	Baja
Hungary	DRC Gyogyszervizsgalo Kozpont Kft.	Balatonfüred
Hungary	Clinexpert Kft.	Budapest
Hungary	Obudai Egeszsegugyi Centrum Kft.	Budapest
Hungary	Kiskunhalasi Semmelweis Korhaz	Kiskunhalas
Hungary	DRC Szekesfehervar	Székesfehérvár
Hungary	MAV Korhaz es Rendelointezet	Szolnok
Hungary	Vital-Medicina Kft.	Veszprem
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-si	Gyeonggi-do
Korea, Republic of	Eulji University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Jeju National University Hospital	Jeju
Korea, Republic of	Severance Hospital, Yonsei University No. 31 Office, Pediatric Oncology Clinic	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do
Latvia	Dr.Saulite-Kandevica Private Practice	Liepaja
Lithuania	Alytus Regional S. Kudirkos Hospital, Public Institution	Alytus
Lithuania	Republican Kaunas Hospital, Public Institution	Kaunas
Lithuania	Klaipeda University Hospital, Public Institution	Klaipeda
Lithuania	Siauliai Republican Hospital, Public Institution	Siauliai
Lithuania	Center Outpatient Clinic, Public Institution	Vilnius
Lithuania	Vilnius University Hospital Santariskiu Clinics, Public Institution	Vilnius
Mexico	Investigacion y Biomedicina de Chihuahua, S.C.	Chihuahua
Mexico	Centro de Estudios de Investigacion Basica y Clinica SC	Guadalajara	Jalisco
Mexico	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco
Mexico	Centro de Investigacion Clínica GRAMEL S.C	Mexico	Distrito Federal
Mexico	Clinicos Asociados BOCM S.C.	Mexico	Distrito Federal
Mexico	Clinstile, S.A. de C.V.	Mexico	Distrito Federal
Mexico	Comite Mexicano Para la Prevencion de Osteoporosis AC	Mexico	Distrito Federal
Mexico	Clinical Research Institute S.C.	Mexico City
Mexico	Accelerium S. de R.L. de C.V.	Monterrey	Nuevo León
Mexico	Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo León
Mexico	Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.	San Luis Potosí
Poland	CERMED	Bialystok
Poland	ZDROWIE Osteo-Medic	Bialystok
Poland	Szpital Uniwersytecki nr 2 im.dr J. Biziela	Bydgoszcz
Poland	MCBK Iwona Czajkowska Anna Podrazka- Szczepaniak S.C.	Grodzisk Mazowiecki
Poland	Polimedica Centrum Badan, Profilaktyki I Leczenia	Kielce
Poland	CCBR - Lodz - PL	Lodz
Poland	Centrum Medyczne AMED	Lodz
Poland	ETYKA Osrodek Badan Klinicznych	Olsztyn
Poland	Szpital Wojewodzki im. Prymasa Kardynala Stefana Wyszynskiego	Sieradz
Poland	Clinmed Research	Skierniewice
Poland	RCMed	Sochaczew
Poland	KO-MED Centra Kliniczne Staszow	Staszow
Poland	Samodzielny Publiczny ZOZ Tomaszow Lubelski	Tomaszow Lubelski
Poland	Nasz lekarz Przychodnie Medyczne	Torun
Poland	McM Polimedica	Warszawa
Poland	Medycyna Kliniczna	Warszawa
Poland	Rheuma Medicus Zaklad Opieki Zdrowotnej	Warszawa
Poland	KO-MED Centra Kliniczne Zamosc	Zamosc
Poland	Santa Familia Centrum Badan, Profilaktyki i Leczenia	Zgierz
Russian Federation	FSBEI HE "Altai State Medical University of the Ministry of Healthcare of Russian Federation"	Barnaul	Altai Region
Russian Federation	FSBEI HE "Ural State Medical University" of Ministry of Health of Russian Federation based on MBI "Central City Clinical Hospital No.6"	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	State Autonomous Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Clinical Hospital No.1"	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	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
Russian Federation	Medical Center LLC "Maksimum Zdoroviya"	Kemerovo	Kemerovo Oblast
Russian Federation	SAHI of Kemerovo region "Regional Clinical Hospital for War Veterans"	Kemerovo	Kemerovskaya Oblast
Russian Federation	Budgetary Healthcare Institution "Kursk Regional Clinical Hospital" of Healthcare Committee of Kursk region	Kursk	Kurskaya Oblast
Russian Federation	FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"	Moscow
Russian Federation	FSAEI HE "First MSMU n.a. I.M. Sechenov of the Ministry of Health of the Russian Federation"	Moscow	Moscovskaya Oblast
Russian Federation	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
Russian Federation	FSBSI "Scientific Research Institute of Rheumatology n.a. V.A. Nasonova"	Moscow
Russian Federation	SBHI of Moscow "City Clinical Hospital #4 of Moscow Healthcare Departament"	Moscow	Moskovskaya Oblast
Russian Federation	SBHI of Moscow "City Clinical Hospital No.1 n.a. Pirogov" Healthcare Department of Moscow	Moscow	Moscovskaya Oblast
Russian Federation	State Budgetary Healthcare Institution "City Clinical Hospital # 15 n.a O.M. Filatov" of Moscow Healtheare Department	Moscow	Moscow Region
Russian Federation	SBHI of Nizhny Novgorod Region "Nizhny Novgorod Regional Clinical Hospital n.a.Semashko"	Nizhniy Novgorod	Nizhegorodskaya Oblast
Russian Federation	SBHI of Nizhegorodsky Region "State Clinical Hospital #5 of Nizhegorodsky District of Nizhny Novgorod"	Nizhny Novgorod	Nizhny Novgorod Oblast
Russian Federation	State Autonomous Healthcare Institution of Novosibirsk region "City Polyclinic #1"	Novosibirsk	Novosibirsk Oblast
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Regional Clinical Hospital"	Omsk	Omskaya Oblast
Russian Federation	LLC "Clinical Diagnostic Center "Ultramed"	Omsk	Omskaya Oblast
Russian Federation	SBHI of the Republic of Karelia "Republican Hospital named after V.A. Baranov"	Petrozavodsk	Republic Of Karelia
Russian Federation	FSBEI HE "Rostov State Medical Unversity" of Ministry of Health of the Russian Federation	Rostov	Rostovskaya Oblast
Russian Federation	FSBEI HE 'Ryazan State Medical University n.a. I.P.Pavlov" of the Ministry of Health of Russian Federation	Ryazan	Ryazan Oblast
Russian Federation	FSBI "National Medical Research Center n.a. V.A.Almazov" of the Ministry of Healthcare of the Russian Federation	Saint Petersburg
Russian Federation	SPb SBHI "Clinical Rheumatological Hospital #25", Fourth Rheumatology Unit	Saint Petersburg	Leningradskaya Oblast
Russian Federation	FSBEI HE "Saratov SMU n.a. V.I.Razumovsky of Ministry of Health of Russian Federation"	Saratov	Saratovskaya Oblast
Russian Federation	State Healthcare Institution "Regional Clinical Hospital"	Saratov	Saratovskaya Oblast
Russian Federation	Private Healthcare Institution "Clinical Hospital Russian Railways-Medicine of City Smolensk"	Smolensk	Smolenskaya Oblast
Russian Federation	FSBEI HE StSMU MOH Russia based on SBHI of Stavropol Region "Stavropol Regional Clinical Hospital"	Stavropol'	Stavropol Region
Russian Federation	State Healthcare Institution of Tula region "Tula Regional Clinical Hospital"	Tula	Tulskaya Oblast
Russian Federation	State Budgetary Healthcare Institution "Republican Clinical Hospital n.a. G.G. Kuvatov"	Ufa	Respublic Of Bashkortostan
Russian Federation	State Healthcare Institution "Ulyanovsk Regional Clinical Hospital"	Ulyanovsk	Ulyanovskaya Oblast
Russian Federation	SBHI of Vladimir Region "Regional Clinical Hospital", Rheumatology Departament	Vladimir	Vladimirskaya Oblast
Russian Federation	State Autonomous Helthcare Institution of Yaroslavl region "Clinical Hospital of Emergency Care n.a. Solovyev"	Yaroslavl	Yaroslavsakaya Oblast
Russian Federation	SBHI "Yaroslavl Regional Clinical Hospital", Rheumatology department	Yaroslavl'	Yaroslavskaya Oblast
Taiwan	Chi Mei Medical Center, Yung Kang Branch	Tainan
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke	Hampshire
United Kingdom	Royal Free Hospital	London	Greater London
United Kingdom	Whipps Cross University Hospital	London	Greater London
United Kingdom	Maidstone Hospital	Maidstone	Kent
United Kingdom	Torbay Hospital	Torquay	Devon
United Kingdom	Arrowe Park Hospital	Wirral	Merseyside
United States	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico
United States	Amarillo Center for Clinical Research	Amarillo	Texas
United States	Austin Regional Clinic, P.A.	Austin	Texas
United States	Accurate Clinical Management., LLC	Baytown	Texas
United States	RASF - Clinical Research Center	Boca Raton	Florida
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	New England Research Associates LLC	Bridgeport	Connecticut
United States	NYU Langone ambulatory care	Brooklyn	New York
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Precision Comprehensive Clinical Research Solutions	Colleyville	Texas
United States	Medvin Clinical Research	Covina	California
United States	Pioneer Research Solutions, Inc.	Cypress	Texas
United States	STAT Research, Inc.	Dayton	Ohio
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Altoona Center for Clinical Research, P.C.	Duncansville	Pennsylvania
United States	Arthritis & Osteoporosis Associates, PA	Freehold	New Jersey
United States	Arthritis Center of North Georgia	Gainesville	Georgia
United States	AA MRC LLC Ahmed Arif Medical Research Center	Grand Blanc	Michigan
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Klein and Associates, M.D., P.A.	Hagerstown	Maryland
United States	C.V Mehta MD Med Corp..	Hemet	California
United States	Reliable Clinical Research, LLC	Hialeah	Florida
United States	CHI St. Vincent Hot Springs	Hot Springs	Arkansas
United States	Accurate Clinical Mangemnt - Partner	Houston	Texas
United States	Accurate Clinical Research, Inc.	Houston	Texas
United States	Houston Institute For Clinical Research	Houston	Texas
United States	Rheumatology Clinic of Houston, P.A.	Houston	Texas
United States	Therapeutic Concepts Rheumatology,LLC	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	Glacier View Research Institute-Rheumatology	Kalispell	Montana
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Advanced Medical Research, LLC	La Palma	California
United States	Accurate Clinical Research, Inc.	League City	Texas
United States	Cape Fear Arthritis Care	Leland	North Carolina
United States	Physician Research Collaboration	Lincoln	Nebraska
United States	Valerius Medical Group	Los Alamitos	California
United States	West Texas Clinical Research	Lubbock	Texas
United States	Marietta Rheumatology Associates, PC	Marietta	Georgia
United States	AZ Arthritis & Rheum' Research	Mesa	Arizona
United States	Medical Research Center of Miami	Miami	Florida
United States	Pharmax Research Clinic	Miami	Florida
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Trinity Medical Group	Minot	North Dakota
United States	The Arthritis & Diabetes Clinic, Inc.	Monroe	Louisiana
United States	Javed Rheumatology Associates	Newark	Delaware
United States	Health Research of Oklahoma, PLLC	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Omega Research Consultants	Orlando	Florida
United States	Arthritis Research of Florida, INC	Palm Harbor	Florida
United States	Stanford University School of Medicine	Palo Alto	California
United States	Family Clinical Trials, LLC.	Pembroke Pines	Florida
United States	Arthritis Group	Philadelphia	Pennsylvania
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona
United States	Dr Alex De Jesus Rheumatology, P.A.	San Antonio	Texas
United States	Rheumatology Center of San Diego	San Diego	California
United States	East Bay Rheumatology Medical Group, Inc.	San Leandro	California
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Low Country Rheumatology, PA	Summerville	South Carolina
United States	Arizona Arthritis & Rheumatology Research, PLLC	Sun City	Arizona
United States	AdventHealth Medical Group, PA	Tampa	Florida
United States	Advanced Rheumatology of Houston	The Woodlands	Texas
United States	Clinical Research Source, Inc.	Toledo	Ohio
United States	DM Clinical Research	Tomball	Texas
United States	North MS Medical Clinics, Inc.	Tupelo	Mississippi
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California
United States	Lovelace Scientific Resources, Inc.	Venice	Florida
United States	Center for Rheumatology Research, Comprehensive Rheumatology Center	West Hills	California
United States	The Center for Rheumatology and Bone Research	Wheaton	Maryland
United States	Medvin Clinical Research	Whittier	California
United States	Carolina Arthritis Associates	Wilmington	North Carolina
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
R-Pharm International, LLC	IQVIA Pvt. Ltd, OCT Clinical Trials

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	up to Week 126
Primary	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.	up to Week 126
Primary	Incidence of Treatment-Emergent Adverse Events of Special Interest (AESI)		up to Week 126
Primary	Incidence of Treatment-Emergent AEs Leading to Withdrawal of the Study Treatment		up to Week 126
Primary	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.	up to Week 126
Primary	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.	up to Week 126
Primary	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.	up to Week 126
Secondary	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)	up to Week 82
Secondary	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)	up to Week 82
Secondary	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)	up to Week 82
Secondary	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)	up to week 82
Secondary	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.	up to Week 82
Secondary	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.	Core baseline, Week 12
Secondary	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.	Core baseline, Week 20
Secondary	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.	Core baseline, Week 28
Secondary	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.	Core baseline, Week 40
Secondary	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.	Core baseline, Week 52
Secondary	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.	Core baseline, Week 64
Secondary	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.	Core baseline, Week 82
Secondary	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.	up to week 82
Secondary	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)	up to week 82