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

NCT01941940 | Completed Phase 3 Results

• 2 other identifiers: ML286992013-001569-17
• Study Type: interventional
• Target: 227
• Locations: 1 country
• Sites: 49

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (7)

• Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

  The CDAI is a numerical sum of 4 outcome parameters: tender joint count (TJC) and swollen joint count (SJC) based on a 28-joint assessment, patient's global assessment of disease activity (PtGDA) and physician global assessment of disease activity (PGDA) assessed on 0-10 centimeters (cm) visual analogue scale (VAS). Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score less than or equal to (\</=) 2.8 indicates disease remission, greater than (\>) 2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 24

• Change From Baseline in CDAI at Week 20

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 20

• Change From Baseline in CDAI at Week 16

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 16

• Change From Baseline in CDAI at Week 12

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 12

• Change From Baseline in CDAI at Week 8

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 8

• Change From Baseline in CDAI at Week 4

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 4

• Change From Baseline in CDAI at Week 2

  The CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGDA and PGDA assessed on 0-10 cm VAS. Higher scores represent greater affectation due to disease activity. CDAI total score = 0-76. CDAI score \</=2.8 indicates disease remission, \>2.8 to 10 indicates low disease activity, \>10 to 22 indicates moderate disease activity, and \>22 indicates high disease activity.

  Baseline, Week 2

Secondary Outcomes (30)

• Number of Participants Achieving Clinical Remission According to CDAI up to Week 52

  Baseline up to Week 52 (Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 38, and 52)

• Change From Baseline in Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Weeks 2, 24, and 52

  Baseline, Weeks 2, 24, and 52

• Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 24, and 52

  Baseline, Weeks 2, 24, and 52

• Percentage of Participants With an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response

  Weeks 2, 24, and 52

• Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28

  Baseline, Weeks 2, 24, and 52

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Tocilizumab at a fixed dose of 162 milligrams (mg) will be administered as subcutaneous (SC) injection alone or along with methotrexate and/or other non-biological DMARDs irrespective of body weight, once every week for a total of 52 weeks. After 52-weeks of treatment, at the discretion of the treating physician, participants can continue the study treatment with SC tocilizumab until it becomes commercially available in Italy.

Drug: Tocilizumab; Drug: DMARDs

Interventions

Tocilizumab DRUG

Tocilizumab at a fixed dose of 162 mg as SC injection will be administered once every week.

Also known as: RoActemra

Tocilizumab

DMARDs DRUG

Non-biologic DMARDs according to standard of care, at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (49)

Uni Degli Studi Di L Aquila; Cattedra Di Reumatologia - Dept. Di Medicina Interna E San

Coppito, Abruzzo, 67100, Italy

Location

P. O. Spirito Santo - Asl Pescara; U.O. Complessa Di Reumatologia

Pescara, Abruzzo, 65100, Italy

Location

Ospedale Regionale Umberto Parini; Reparto Endocrinologia e Diabetologia - Amb. Reumatologia

Aosta, Aosta Valley, 11100, Italy

Location

Azienda Ospedaliera Policlinico; Servizio Reumatologia

Bari, Apulia, 70124, Italy

Location

ASL Lecce- Presidio Ospedaliero di Casarano-Servizio di Reumatologia ed Osteoporosi

Casarano (LE), Apulia, 73042, Italy

Location

Ospedali Riuniti di Foggia; Dipartimento Medicina Interna Reumatologia

Foggia, Apulia, 71100, Italy

Location

Ospedali Riuniti Di Foggia; Struttura Di Reumatologia

Foggia, Apulia, 71100, Italy

Location

Azienda Ospedaliera Bianchi Melacrino Morelli; Unità Operativa di Reumatologia

Reggio Calabria, Calabria, 89133, Italy

Location

Az. Ospedaliera S. Giuseppe Moscati; Dip. Med. Gen. Struttura Semplice Reumatologia

Avellino, Campania, 83100, Italy

Location

Azienda Ospedaliera Rummo; Divisione Di Reumatologia

Benevento, Campania, 82100, Italy

Location

Azienda Ospedaliera A. Cardarelli; Medicina III - Divisione di Reumatologia

Napoli, Campania, 80131, Italy

Location

Policlinico Universitario-II Università di Napoli; Reumatologia

Napoli, Campania, 80131, Italy

Location

Osp Riuniti S.Giovanni di Dio e Ruggi d'Aragona; Rep. Medicina Interna

Salerno, Campania, 84131, Italy

Location

Irccs Fondazione Salvatore Maugeri-Istituto Scientifico Di Telese;U.O. Riabilitazione Reumatologica

Telese Terme, Campania, 82037, Italy

Location

A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2

Bologna, Emilia-Romagna, 40138, Italy

Location

A.O. Universitaria Policlinico Di Modena; Reumatologia

Modena, Emilia-Romagna, 41100, Italy

Location

Arcispedale Santa Maria Nuova; Reumatologia

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia

Udine, Friuli Venezia Giulia, 33100, Italy

Location

Policlinico Campus Bio-Medico Di Trigoria; Medicina Clinica E Reumatologia

Rome, Lazio, 00128, Italy

Location

Policlinico Tor Vergata; Divisione Di Reumatologia

Rome, Lazio, 00133, Italy

Location

Ospedale S.Pietro Fatebenefratelli; Divisione di Reumatologia

Rome, Lazio, 00189, Italy

Location

Ospedale La Colletta; Reparto Di Reumatologia

Arenzano, Liguria, 16011, Italy

Location

Università Degli Studi Di Genova - Dimi; Reumatologia

Genoa, Liguria, 16132, Italy

Location

Ospedale San Paolo; Divisione di Reumatologia

Savona, Liguria, 17100, Italy

Location

Asst Papa Giovanni XXIII; Dh Reumatologia

Bergamo, Lombardy, 24127, Italy

Location

Ospedale Civile "La Memoria" Di Gavardo;Immunoematologia Trasfusionale-Allergologia E Reumatologia

Gavardo, Lombardy, 25085, Italy

Location

Ospedale Di Magenta Fornaroli; U.O. Di Reumatologia

Magenta, Lombardy, 20013, Italy

Location

Asst Centro Specialistico Ortopedico Traumato-Logico Gaetano Pini/Cto; Divisione Di Reumatologia

Milan, Lombardy, 20122, Italy

Location

Ospedale Maggiore Policlinico; Unità Operativa Complessa di Allergologia e Immunologia Clinica

Milan, Lombardy, 20122, Italy

Location

ASST FATEBENEFRATELLI SACCO; Reumatologia (Sacco)

Milan, Lombardy, 20157, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Reumatologia

Milan, Lombardy, 20162, Italy

Location

ASST DI MONZA; Reumatologia (Medicina I)

Monza, Lombardy, 20052, Italy

Location

Irccs Policlinico San Matteo; Reumatologia Adulti

Pavia, Lombardy, 27100, Italy

Location

ASST DI VIMERCATE; Medicina Generale

Vimercate, Lombardy, 20059, Italy

Location

Azienda Ospedaliera Maggiore Della Carita; Day Hospital Immunologia

Novara, Piedmont, 28100, Italy

Location

Azienda Ospedaliera San Giovanni Battista; Reparto Reumatologia

Turin, Piedmont, 10126, Italy

Location

Ordine Mauriziano Ospedale Umberto I; Centro Di Reumatologia

Turin, Piedmont, 10128, Italy

Location

A.O. Universitaria Policlinico Monserrato Di Cagliari; Reumatologia I

Cagliari, Sardinia, 09042, Italy

Location

Azienda Ospedaliero Universitaria di Sassari; UOC Reumatologia

Sassari, Sardinia, 07100, Italy

Location

Ospedale Vittorio Emanuele Ii; U.O. Reumatologia Clinica Medica Condorelli

Catania, Sicily, 95124, Italy

Location

Azienda Osped. Univ. Policlinico G. Martino; Centro Prevenzione E Cura Osteoporosi

Messina, Sicily, 98100, Italy

Location

Arnas Ospedale Civico; Medicina Interna II

Palermo, Sicily, 90127, Italy

Location

Ospedale Regionale Torrette; SOD Clinica Medica del Dipartimento di Medicina Interna e Specialisti

Ancona, The Marches, 60020, Italy

Location

Ospedale Murri - Universita Politecnica Delle Marche; Clinica Reumatologica Ii

Iesi, The Marches, 60035, Italy

Location

Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia

Florence, Tuscany, 50139, Italy

Location

Az. Osp. Pisana Ospedale S. Chiara; U.O. Di Reumatologia

Pisa, Tuscany, 56100, Italy

Location

Osp S. Maria Misericordia Dip. Medicina Clinica Sperimentale Cattedra Reumatologia

Perugia, Umbria, 06122, Italy

Location

Azienda Ospedaliera Universitaria Borgo Trento; Dipartimento di Medicina Sezione di Reumatologia

Verona, Veneto, 37126, Italy

Location

Policlinico G.B. Rossi; Divisione Immunologia Clinica Sperimentale Medicina B

Verona, Veneto, 37134, Italy

Location

Related Publications (2)

• 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.

  PMID: 30649524 DERIVED

• 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.

  PMID: 29244149 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab; Antirheumatic Agents

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2013
• First Posted: September 13, 2013
• Study Start: September 5, 2013
• Primary Completion: September 9, 2015
• Study Completion: July 5, 2016
• Last Updated: July 11, 2017
• Results First Posted: December 15, 2016

Record last verified: 2017-06

Locations

IT (49)