Clinical trial NCT01941940: A Study to Evaluate Efficacy of Tocilizumab Administered as Monotherapy or in Combination With Methotrexate and/or Other Disease Modifying Antirheumatic Drugs (DMARDs) in Rheumatoid Arthritis (RA) Participants
Official title: A National, Open-Label, Single-Arm, Phase IIIb Study to Evaluate the Efficacy of Weekly Tocilizumab Subcutaneous, Administered as Monotherapy or in Combination With Methotrexate and/or Other DMARDs in Rheumatoid Arthritis (RA) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-09-13
Enrollment: 227
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single arm, Phase 3b study will evaluate the efficacy of tocilizumab (RoActemra), administered as monotherapy or in combination with methotrexate and/or other DMARDs, in participants with moderate to severe active RA.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
* Moderate to severe RA (CDAI at least \[\>/=\] 10 and DAS28 \>/=3.2) at screening
* Tumor necrosis factor inhibitors-inadequate responder (TNF-IR), methotrexate-inadequate responder (MTX-IR), and/or DMARDs-inadequate responder (DMARDs-IR)
* Oral corticosteroids (less than or equal to \[\</=\] 10 mg per day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for \>/=4 weeks prior to baseline
* Permitted non-biologic DMARDs are allowed if at a stable dose for \>/=4 weeks prior to baseline
* Receiving treatment on an outpatient basis, not including tocilizumab
* Females of childbearing potential and males with female partners of childbearing potential must agree to use a reliable means of contraception for at least 3 months following the last dose of tocilizumab

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 12 months following baseline
* Rheumatic autoimmune disease other than RA; secondary Sjögren's syndrome with RA is permitted
* Functional Class IV as defined by the ACR Classification of Functional Status in RA
* Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
* Prior history of or current inflammatory joint disease other than RA
* Exposure to tocilizumab (either intravenous \[IV\] or SC) at any time prior to baseline
* Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
* Previous treatment with any cell-depleting therapies
* Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
* Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal disease
* Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
* Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
* Active tuberculosis (TB) requiring treatment within the previous 3 years
* Positive for hepatitis B surface antigen or hepatitis C antibody
* Primary or secondary immunodeficiency (history of or currently active)
* Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
* Pregnant or breast feeding women
* Neuropathies or other conditions that might interfere with pain evaluation

Primary outcomes:
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in CDAI at Week 20
timeFrame: Baseline, Week 20
measure: Change From Baseline in CDAI at Week 16
timeFrame: Baseline, Week 16
measure: Change From Baseline in CDAI at Week 12
timeFrame: Baseline, Week 12
measure: Change From Baseline in CDAI at Week 8
timeFrame: Baseline, Week 8
measure: Change From Baseline in CDAI at Week 4
timeFrame: Baseline, Week 4
measure: Change From Baseline in CDAI at Week 2
timeFrame: Baseline, Week 2
Secondary outcomes:
measure: Number of Participants Achieving Clinical Remission According to CDAI up to Week 52
timeFrame: Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52)
measure: Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response
timeFrame: Weeks 2, 24, and 52
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Change From Baseline in Total TJC at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Change From Baseline in Total SJC at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Association Between Disease Activity Parameters: DAS28-ESR and CDAI, Assessed Using Correlation Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameters: DAS28-ESR and SDAI, Assessed Using Correlation Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameters: CDAI and SDAI, Assessed Using Correlation Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (DAS28-ESR) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (CDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameters (ACR20, ACR50, and ACR70), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Association Between Disease Activity Parameter (SDAI) and Treatment Response Parameter (EULAR), Assessed Using Regression Coefficient
timeFrame: Weeks 2, 24, 52
measure: Percentage of DMARDs Dose Reductions and/or Discontinuation Events by Reasons
timeFrame: Baseline up to Week 52
measure: Percentage of Non-DMARDs Dose Reductions and/or Discontinuation Events by Reasons
timeFrame: Baseline up to Week 52
measure: Change From Baseline in PtGDA VAS Score at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Change From Baseline in PGDA VAS Score at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Participant Pain VAS Score at Weeks 2, 24, and 52
timeFrame: Weeks 2, 24, and 52
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Missed Working Days Assessed Using Short Form-Health and Labor Questionnaire (SF-HLQ) Score at Weeks 24 and 52
timeFrame: Weeks 24 and 52
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Total Score at Weeks 2, 24, and 52
timeFrame: Baseline, Weeks 2, 24, and 52
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) at Weeks 24 and 52
timeFrame: Baseline, Weeks 24 and 52
measure: Treatment Compliance, as Assessed Using Participant Diary Cards and Return Records
timeFrame: Weeks 24 and 52
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) of Special Interest
timeFrame: Baseline up to 95 weeks
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to Tocilizumab
timeFrame: Baseline, Weeks 12, 24, 38, 52, at 8 weeks after last dose (up to Week 60), at early withdrawal (up to Week 52), at Follow-up Visits 1 (Week 64), 2 (Week 76), and 3 (Week 88)
measure: Mean Tocilizumab Concentration
timeFrame: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)
measure: Mean Soluble Interleukin-6 Receptor (sIL-6R) Concentration
timeFrame: Baseline, Weeks 12, 24, 38, 52, at early withdrawal (up to Week 52), at Follow-up Visit 2 (Week 76)
Other outcomes:
Locations:
city: Coppito
country: Italy
facility: Uni Degli Studi Di L Aquila; Cattedra Di Reumatologia - Dept. Di Medicina Interna E San
state: Abruzzo
city: Pescara
country: Italy
facility: P. O. Spirito Santo - Asl Pescara; U.O. Complessa Di Reumatologia
state: Abruzzo
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli; Unità Operativa di Reumatologia
state: Calabria
city: Avellino
country: Italy
facility: Az. Ospedaliera S. Giuseppe Moscati; Dip. Med. Gen. Struttura Semplice Reumatologia
state: Campania
city: Benevento
country: Italy
facility: Azienda Ospedaliera Rummo; Divisione Di Reumatologia
state: Campania
city: Napoli
country: Italy
facility: Azienda Ospedaliera A. Cardarelli; Medicina III - Divisione di Reumatologia
state: Campania
city: Napoli
country: Italy
facility: Policlinico Universitario-II Università di Napoli; Reumatologia
state: Campania
city: Salerno
country: Italy
facility: Osp Riuniti S.Giovanni di Dio e Ruggi d'Aragona; Rep. Medicina Interna
state: Campania
city: Telese Terme
country: Italy
facility: Irccs Fondazione Salvatore Maugeri-Istituto Scientifico Di Telese;U.O. Riabilitazione Reumatologica
state: Campania
city: Bologna
country: Italy
facility: A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2
state: Emilia-Romagna
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena; Reumatologia
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova; Reumatologia
state: Emilia-Romagna
city: Udine
country: Italy
facility: Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Policlinico Campus Bio-Medico Di Trigoria; Medicina Clinica E Reumatologia
state: Lazio
city: Roma
country: Italy
facility: Policlinico Tor Vergata; Divisione Di Reumatologia
state: Lazio
city: Roma
country: Italy
facility: Ospedale S.Pietro Fatebenefratelli; Divisione di Reumatologia
state: Lazio
city: Arenzano
country: Italy
facility: Ospedale La Colletta; Reparto Di Reumatologia
state: Liguria
city: Genova
country: Italy
facility: Università Degli Studi Di Genova - Dimi; Reumatologia
state: Liguria
city: Savona
country: Italy
facility: Ospedale San Paolo; Divisione di Reumatologia
state: Liguria
city: Bergamo
country: Italy
facility: Asst Papa Giovanni XXIII; Dh Reumatologia
state: Lombardia
city: Gavardo
country: Italy
facility: Ospedale Civile "La Memoria" Di Gavardo;Immunoematologia Trasfusionale-Allergologia E Reumatologia
state: Lombardia
city: Magenta
country: Italy
facility: Ospedale Di Magenta Fornaroli; U.O. Di Reumatologia
state: Lombardia
city: Milano
country: Italy
facility: Asst Centro Specialistico Ortopedico Traumato-Logico Gaetano Pini/Cto; Divisione Di Reumatologia
state: Lombardia
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica
state: Lombardia
city: Milano
country: Italy
facility: ASST FATEBENEFRATELLI SACCO; Reumatologia (Sacco)
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; Reumatologia
state: Lombardia
city: Monza
country: Italy
facility: ASST DI MONZA; Reumatologia (Medicina I)
state: Lombardia
city: Pavia
country: Italy
facility: Irccs Policlinico San Matteo; Reumatologia Adulti
state: Lombardia
city: Vimercate
country: Italy
facility: ASST DI VIMERCATE; Medicina Generale
state: Lombardia
city: Ancona
country: Italy
facility: Ospedale Regionale Torrette; SOD Clinica Medica del Dipartimento di Medicina Interna e Specialisti
state: Marche
city: Jesi
country: Italy
facility: Ospedale Murri - Universita Politecnica Delle Marche; Clinica Reumatologica Ii
state: Marche
city: Novara
country: Italy
facility: Azienda Ospedaliera Maggiore Della Carita; Day Hospital Immunologia
state: Piemonte
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni Battista; Reparto Reumatologia
state: Piemonte
city: Torino
country: Italy
facility: Ordine Mauriziano Ospedale Umberto I; Centro Di Reumatologia
state: Piemonte
city: Bari
country: Italy
facility: Azienda Ospedaliera Policlinico; Servizio Reumatologia
state: Puglia
city: Casarano (LE)
country: Italy
facility: ASL Lecce- Presidio Ospedaliero di Casarano-Servizio di Reumatologia ed Osteoporosi
state: Puglia
city: Foggia
country: Italy
facility: Ospedali Riuniti di Foggia; Dipartimento Medicina Interna Reumatologia
state: Puglia
city: Foggia
country: Italy
facility: Ospedali Riuniti Di Foggia; Struttura Di Reumatologia
state: Puglia
city: Cagliari
country: Italy
facility: A.O. Universitaria Policlinico Monserrato Di Cagliari; Reumatologia I
state: Sardegna
city: Sassari
country: Italy
facility: Azienda Ospedaliero Universitaria di Sassari; UOC Reumatologia
state: Sardegna
city: Catania
country: Italy
facility: Ospedale Vittorio Emanuele Ii; U.O. Reumatologia Clinica Medica Condorelli
state: Sicilia
city: Messina
country: Italy
facility: Azienda Osped. Univ. Policlinico G. Martino; Centro Prevenzione E Cura Osteoporosi
state: Sicilia
city: Palermo
country: Italy
facility: Arnas Ospedale Civico; Medicina Interna II
state: Sicilia
city: Firenze
country: Italy
facility: Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia
state: Toscana
city: Pisa
country: Italy
facility: Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia
state: Toscana
city: Perugia
country: Italy
facility: Osp S. Maria Misericordia Dip. Medicina Clinica Sperimentale Cattedra Reumatologia
state: Umbria
city: Aosta
country: Italy
facility: Ospedale Regionale Umberto Parini; Reparto Endocrinologia e Diabetologia - Amb. Reumatologia
state: Valle D'Aosta
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Borgo Trento; Dipartimento di Medicina Sezione di Reumatologia
state: Veneto
city: Verona
country: Italy
facility: Policlinico G.B. Rossi; Divisione Immunologia Clinica Sperimentale Medicina B
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
citation: Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.