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

NCT01995201 | Completed Phase 3 Results

• 2 other identifiers: ML287092013-002429-52
• Study Type: interventional
• Target: 401
• Locations: 3 countries
• Sites: 53

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24

  The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.

  Week 20 and Week 24

Secondary Outcomes (42)

• Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR)

  From week 24 up to week 48

• Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48

  From week 28 up to week 48

• Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48

  From week 28 up to week 48

• Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24

  From week 2 until week 24

• Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48

  From week 28 until week 48

Study Arms (3)

Part 1: All patients

EXPERIMENTAL

Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]

Part 2 A: Sustained clinical remission

EXPERIMENTAL

Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]

Part 2 B: Low disease activity

EXPERIMENTAL

Drug: DMARD; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]

Interventions

DMARD DRUG

non-biological disease-modifying antirheumatic drugs at stable dose

Part 1: All patients; Part 2 A: Sustained clinical remission; Part 2 B: Low disease activity

methotrexate DRUG

stable dose

Part 1: All patients; Part 2 A: Sustained clinical remission; Part 2 B: Low disease activity

tocilizumab [RoActemra/Actemra] DRUG

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

Part 1: All patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (53)

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Co Leitrim, Ireland

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Cork, Ireland

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Dublin, 24, Ireland

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Dublin, 4, Ireland

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Limerick, 0, Ireland

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Waterford, Ireland

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Almada, 2801-951, Portugal

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Amadora, 3814-501, Portugal

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Lisbon, 1050-34, Portugal

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Lisbon, 1649-035, Portugal

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Porto, 4099-001, Portugal

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Porto, 4200-319, Portugal

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Elche, Alicante, 03203, Spain

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Mérida, Badajoz, 06800, Spain

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Palma de Mallorca, Balearic Islands, 07198, Spain

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Sabadell, Barcelona, 08208, Spain

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Sant Joan Despí, Barcelona, 08970, Spain

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Terrassa, Barcelona, 08221, Spain

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Jerez de la Frontera, Cadiz, 11407, Spain

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Torrelavega, Cantabria, 39300, Spain

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Donostia / San Sebastian, Guipuzcoa, 20080, Spain

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A Coruña, La Coruña, 15006, Spain

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Santiago de Compostela, La Coruña, 15706, Spain

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Las Palmas de Gran Canaria, Las Palmas, 35016, Spain

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Fuenlabrada, Madrid, 28942, Spain

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Cartagena, Murcia, 30203, Spain

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El Palmar, Murcia, 30120, Spain

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Santa Cruz de Tenerife, Tenerife, 38010, Spain

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Valenica, Valencia, 46009, Spain

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Bilbao, Vizcaya, 48013, Spain

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Alicante, 03010, Spain

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Barcelona, 08025, Spain

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Barcelona, 08036, Spain

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Burgos, 06006, Spain

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Córdoba, 14004, Spain

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Granada, 18014, Spain

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Guadalajara, 19002, Spain

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Madrid, 28006, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Madrid, 28222, Spain

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Madrid, 28905, Spain

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Málaga, 29009, Spain

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Salamanca, 37007, Spain

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Seville, 41009, Spain

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Seville, 41010, Spain

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Seville, 41013, Spain

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Tarragona, 43700, Spain

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Toledo, 45004, Spain

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Valencia, 46010, Spain

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Zaragoza, 50009, Spain

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Related Publications (3)

• 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.

  PMID: 31087542 DERIVED

• 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

Antirheumatic Agents; Methotrexate; tocilizumab

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; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 1, 2013
• First Posted: November 26, 2013
• Study Start: September 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: March 1, 2016
• Last Updated: January 26, 2018
• Results First Posted: January 26, 2018

Record last verified: 2017-06

Locations

PT (6); ES (41); IE (6)