A Study of Tocilizumab (RoActemra/Actemra) in Monotherapy or in Combination With Methotrexate or Other Non-Biologic DMARDs in Participants With Active Rheumatoid Arthritis and an Inadequate Response to Current Non-Biologic DMARD Therapy or the First Anti-TNF Biologic Agent

NCT ID: NCT02046603

Last Updated: 2018-12-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-04

Study Completion Date

2016-08-04

Brief Summary

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This open-label study will evaluate the efficacy and safety of tocilizumab as monotherapy or in combination with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) in participants with active rheumatoid arthritis (RA) and an inadequate response to current non-biologic DMARD therapy or the first anti-tumour necrosis factor (anti-TNF) agent. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously once a week for 52 weeks.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Tocilizumab Monotherapy

Participants will receive a weekly SC injection of tocilizumab 162 mg as monotherapy for 52 weeks.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.

Tocilizumab in Combination With Methotrexate or Other DMARDs

Participants will receive a weekly SC injection of tocilizumab 162 mg in combination with methotrexate or other non-biologic DMARDs for 52 weeks.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.

DMARDs

Intervention Type DRUG

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study. The study protocol does not specify any particular therapy.

Oral Corticosteroids

Intervention Type DRUG

Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.

Methotrexate

Intervention Type DRUG

Methotrexate per investigator's discretion.

Interventions

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Tocilizumab

Tocilizumab 162 mg will be administered once a week by SC injection and as a single fixed dose, irrespective of body weight, for the treatment duration of 52 weeks.

Intervention Type DRUG

DMARDs

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study. The study protocol does not specify any particular therapy.

Intervention Type DRUG

Oral Corticosteroids

Stable oral corticosteroids doses (≤10 mg/day prednisone or equivalent) are allowed. The study protocol does not specify any additional detail on types of oral corticosteroids.

Intervention Type DRUG

Methotrexate

Methotrexate per investigator's discretion.

Intervention Type DRUG

Other Intervention Names

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RoActemra, Actemra

Eligibility Criteria

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Inclusion Criteria

* Active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
* Participants who have an inadequate response to current non-biologic DMARD therapy or the first anti-TNF agent (in monotherapy or in combination with MTX or other non-biologic DMARDs). Inadequate response to anti-TNF treatment is defined as DAS28 score improvement of less than 1.2 or participants achieving a DAS28 score improvement of 1.2 but not achieving low disease activity (current DAS28-ESR above 3.2) according to a treat-to-target strategy and have not been previously exposed to treatment with tocilizumab. Inadequate response to non-biologic DMARD therapy will be assessed according to local guidelines and the participants will need to be eligible for biologic therapy according to local guidelines
* Oral corticosteroids (≤10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to recommended dose) are permitted if on stable dose regimen for greater than or equal to \[≥\] 4 weeks prior to baseline
* Permitted non-biologic DMARDs are allowed if on stable dose for at least 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 reliable means of contraception as defined by protocol during the study and 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 6 months following baseline
* Rheumatic autoimmune disease other than RA
* 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 or current inflammatory joint disease other than RA
* Exposure to tocilizumab either intravenous 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
* 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
* Known active current or history of recurrent infections
* 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 or hepatitis C virus infection
* Primary or secondary immunodeficiency (history of or currently active)
* Pregnant or lactating women
* Inadequate hematologic, renal or liver function
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Christchurch Hospital; Rheumatology

Bournemouth, , United Kingdom

Site Status

Royal Sussex County Hospital; Clinical Investigation Research Unit

Brighton, , United Kingdom

Site Status

Queens Hospital

Burton-on-Trent, , United Kingdom

Site Status

West Suffolk Hospital

Bury Saint Edmonds, , United Kingdom

Site Status

Addenbrooke'S Hospital; Rheumatology Research Unit

Cambridge, , United Kingdom

Site Status

Cannock Chase Hospital; Rheumatology

Cannock, , United Kingdom

Site Status

University Hospital of Wales; Dept of Rhematology

Cardiff, , United Kingdom

Site Status

Broomfield Hospital

Chelmsford, , United Kingdom

Site Status

Countess of Chester Hospital; Dept of Rheumatology

Chester, , United Kingdom

Site Status

Dewsbury & District Hospital; Dept of Rheumatology

Dewsbury, , United Kingdom

Site Status

Russells Hall Hospital; Rheumatology Department

Dudley, , United Kingdom

Site Status

Ninewells Hospital

Dundee, , United Kingdom

Site Status

Eastbourne District General Hospital; Dept of Rheumatology

Eastbourne, , United Kingdom

Site Status

Western General Hospital; Pharmacy Department

Edinburgh, , United Kingdom

Site Status

Gartnavel General Hospital; Rheumatology

Glasgow, , United Kingdom

Site Status

Diana Princess of Wales Hosp.

Grimsby, , United Kingdom

Site Status

Princess Alexandra Hospital

Harlow, , United Kingdom

Site Status

Northwick Park Hospital

Harrow, , United Kingdom

Site Status

Hemel Hempstead General Hospital; Rheumatology Dept

Hemel Hempstead, , United Kingdom

Site Status

Hull Royal Infirmary; Rheumatology Department

Hull, , United Kingdom

Site Status

Llandudno General Hospital

Llandudno, , United Kingdom

Site Status

Whipps Cross Hospital; Rheumatology Dept

London, , United Kingdom

Site Status

Royal Free Hospital; Department of Rheumatology

London, , United Kingdom

Site Status

Maidstone Hospital; Dept of Rheumatology

Maidstone, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Freeman Hospital; Dept of Rheumatology

Newcastle upon Tyne, , United Kingdom

Site Status

North Tyneside General Hospital

North Shields, , United Kingdom

Site Status

Norfolk & Norwich Hospital; Rheumatology

Norwich, , United Kingdom

Site Status

Integrated Care Centre

Oldham, , United Kingdom

Site Status

Solihull Hospital

Solihull, , United Kingdom

Site Status

Haywood Hospital; Staffordshire Rheumatology Centre

Stoke-on-Trent, , United Kingdom

Site Status

Great Western Hospital; Dept of Rheumatology

Swindon, , United Kingdom

Site Status

Torbay Hospital; Dept of Rhematology

Torquay, , United Kingdom

Site Status

Royal Cornwall Hospital; Rhuematololgy Dept

Truro, , United Kingdom

Site Status

Warrington Hospital

Warrington, , United Kingdom

Site Status

Wrightington Hospital; Rheumatology

Wigan, , United Kingdom

Site Status

Wishaw General Hospital

Wishaw, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Isaacs JD, Salih A, Sheeran T, Patel YI, Douglas K, McKay ND, Naisbett-Groet B, Choy E. Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study. Rheumatol Adv Pract. 2019 Apr 19;3(1):rkz010. doi: 10.1093/rap/rkz010. eCollection 2019.

Reference Type DERIVED
PMID: 31431998 (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

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2013-000054-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28641

Identifier Type: -

Identifier Source: org_study_id