A Study of Subcutaneous RoActemra/Actemra (Tocilizumab) as Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Patients With Active Rheumatoid Arthritis

NCT ID: NCT01995201

Last Updated: 2018-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 401 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-03-31

Brief Summary

This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained clinical remission but achieve low disease activity (DAS-ESR </= 3.2) will continue the initial treatment of RoActemra/Actemra 162 mg sc weekly for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: All patients

Group Type: EXPERIMENTAL

DMARD

Intervention Type: DRUG

non-biological disease-modifying antirheumatic drugs at stable dose

methotrexate

Intervention Type: DRUG

stable dose

tocilizumab [RoActemra/Actemra]

Intervention Type: DRUG

162 mg subcutaneously (SC) qw, Weeks 1-24

Part 2 A: Sustained clinical remission

Group Type: EXPERIMENTAL

DMARD

Intervention Type: DRUG

non-biological disease-modifying antirheumatic drugs at stable dose

methotrexate

Intervention Type: DRUG

stable dose

tocilizumab [RoActemra/Actemra]

Intervention Type: DRUG

162 mg SC qw or q2w, Weeks 24-48

Part 2 B: Low disease activity

Group Type: EXPERIMENTAL

DMARD

Intervention Type: DRUG

non-biological disease-modifying antirheumatic drugs at stable dose

methotrexate

Intervention Type: DRUG

stable dose

tocilizumab [RoActemra/Actemra]

Intervention Type: DRUG

162 mg SC qw, Weeks 24-48

Interventions

DMARD

non-biological disease-modifying antirheumatic drugs at stable dose

Intervention Type: DRUG

methotrexate

stable dose

Intervention Type: DRUG

tocilizumab [RoActemra/Actemra]

162 mg subcutaneously (SC) qw, Weeks 1-24

Intervention Type: DRUG

tocilizumab [RoActemra/Actemra]

162 mg SC qw or q2w, Weeks 24-48

Intervention Type: DRUG

tocilizumab [RoActemra/Actemra]

162 mg SC qw, Weeks 24-48

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients, >/= 18 years of age
• Active rheumatoid arthritis (DAS28-ESR > 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of > 6 months duration
• Patients with intolerance or inadequate response to methotrexate or other non-biologic DMRADs or inadequate response to a first ant-TNF agent
• Oral corticosteroids (</= 10 mg/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 DMRAD is allowed if at stable dose for at least 4 weeks prior to baseline
• Females of childbearing potential and males with female partners of childbearing potential must be using a reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of RoActemra/Actemra
• Patients with intolerance or inadequate response to methotrexate or other non-biologic DMARDs or inadequate response to first anti-TNF agent

Exclusion Criteria

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
• Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; secondary Sjögren's syndrome with RA is permitted
• Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
• Prior history of 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 with four weeks (or five-half lives of the investigational drug, whichever is longer) of screening
• Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
• Previous treatment with Abatacept
• History of severe allergic of anaphylactic reactions to human, humanized, or murine monoclonal antibodies
• Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal (GI) disease
• History of diverticulitis, diverticulitis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections or nail beds)
• 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 TB requiring treatment within the previous 3 years
• Positive hepatitis B or hepatitis C
• Primary or secondary immunodeficiency (history of or currently active)
• Evidence of active malignant disease, malignancies diagnosed with the previous 10 years (including hematological malignancies and solid tumors, except basal of squamous cell carcinoma of the skin diagnosed within the previous 20 years
• Pregnant and lactating women
• History of alcohol, drug, or chemical abuse within 1 year prior to screening
• Neuropathies or other conditions that might interfere with pain evaluation
• Inadequate hematological, real of liver function

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Co Leitrim, , Ireland

Cork, , Ireland

Dublin, , Ireland

Dublin, , Ireland

Limerick, , Ireland

Waterford, , Ireland

Almada, , Portugal

Amadora, , Portugal

Lisbon, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Porto, , Portugal

Elche, Alicante, Spain

Mérida, Badajoz, Spain

Palma de Mallorca, Balearic Islands, Spain

Sabadell, Barcelona, Spain

Sant Joan Despí, Barcelona, Spain

Terrassa, Barcelona, Spain

Jerez de la Frontera, Cadiz, Spain

Torrelavega, Cantabria, Spain

Donostia / San Sebastian, Guipuzcoa, Spain

A Coruña, La Coruña, Spain

Santiago de Compostela, La Coruña, Spain

Las Palmas de Gran Canaria, Las Palmas, Spain

Fuenlabrada, Madrid, Spain

Cartagena, Murcia, Spain

El Palmar, Murcia, Spain

Santa Cruz de Tenerife, Tenerife, Spain

Valenica, Valencia, Spain

Bilbao, Vizcaya, Spain

Alicante, , Spain

Barcelona, , Spain

Barcelona, , Spain

Burgos, , Spain

Córdoba, , Spain

Granada, , Spain

Guadalajara, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Málaga, , Spain

Salamanca, , Spain

Seville, , Spain

Seville, , Spain

Seville, , Spain

Tarragona, , Spain

Toledo, , Spain

Valencia, , Spain

Zaragoza, , Spain

Countries

Ireland; Portugal; Spain

References

Sanmarti R, Veale DJ, Martin-Mola E, Escudero-Contreras A, Gonzalez C, Ercole L, Alonso R, Fonseca JE; ToSpace Study Group. Reducing or Maintaining the Dose of Subcutaneous Tocilizumab in Patients With Rheumatoid Arthritis in Clinical Remission: A Randomized, Open-Label Trial. Arthritis Rheumatol. 2019 Oct;71(10):1616-1625. doi: 10.1002/art.40905. Epub 2019 Sep 24.

Reference Type: DERIVED

PMID: 31087542 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30649524 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29244149 (View on PubMed)

Other Identifiers

2013-002429-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28709

Identifier Type: -

Identifier Source: org_study_id