NCT01987479

Brief Summary

This multi-center, open-label single arm Phase IIIb study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab administered as monotherapy and/or in combination with methotrexate or other non-biologic disease modifying antirheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) with an inadequate response to non-biologic DMARDs.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P25-P50 for phase_3 rheumatoid-arthritis

Timeline
Completed

Started Jan 2014

Geographic Reach
1 country

20 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 8, 2013

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 19, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

January 30, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 26, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 26, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

June 19, 2017

Completed
Last Updated

June 19, 2017

Status Verified

May 1, 2017

Enrollment Period

2.3 years

First QC Date

November 8, 2013

Results QC Date

May 19, 2017

Last Update Submit

May 19, 2017

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Adverse Events

    An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Adverse events included serious as well as non-serious adverse events.

    Baseline up to Week 32

Secondary Outcomes (21)

  • Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal

    Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

  • Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response

    Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

  • Percentage of Participants Achieving an ACR50 Response

    Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

  • Percentage of Participants Achieving an ACR70 Response

    Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

  • Percentage of Participants Achieving an ACR90 Response

    Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)

  • +16 more secondary outcomes

Study Arms (1)

Tocilizumab Alone or in Combination with Methotrexate or DMARD

EXPERIMENTAL

Participants will receive a weekly SC injection of tocilizumab 162 milligrams (mg) as monotherapy or in combination with methotrexate or other non-biologic DMARDs for 24 weeks.

Drug: Non-Biologic DMARDsDrug: TocilizumabDrug: Methotrexate

Interventions

Non-Biologic DMARDsDRUG

Treatment with non-biologic DMARDs, at a stable dose that was initiated at least 4 weeks prior to baseline, is permitted during the study and is at the investigator's discretion.

Tocilizumab Alone or in Combination with Methotrexate or DMARD
TocilizumabDRUG

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 24 weeks.

Also known as: RoActemra, Actemra
Tocilizumab Alone or in Combination with Methotrexate or DMARD
MethotrexateDRUG

Methotrexate will be administered per investigator's discretion.

Tocilizumab Alone or in Combination with Methotrexate or DMARD

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
  • Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥\]) 4 weeks prior to Baseline.
  • Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.

You may not qualify if:

  • Presence of clinically significant medical conditions.
  • History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation.
  • Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
  • Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
  • Clinically significant findings on laboratory tests.
  • Positive hepatitis B surface antigen or hepatitis C antibody.
  • Active tuberculosis requiring treatment within the previous 3 years.
  • Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
  • History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
  • Neuropathies or other conditions that might interfere with pain evaluation.
  • 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, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). 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 years.
  • Prior history of or current inflammatory joint disease other than RA.
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

ZGT Almelo; Reumatologie

Almelo, 7609 PP, Netherlands

Location

Jan Van Breemen Instituut

Amsterdam, 1056 AB, Netherlands

Location

Gelre Ziekenhuizen; Reumatologie

Apeldoorn, 7334 DZ, Netherlands

Location

Amphia ziekenhuis, locatie langendijk

Breda, 4819 EV, Netherlands

Location

Albert Schweitzer Ziekenhuis ; Dordwijk

Dordrecht, 3318AT, Netherlands

Location

Universitair Medisch Centrum Groningen; Department of Rheumatology

Groningen, 9700RB, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 MG, Netherlands

Location

Kennemer Gasthuis

Haarlem, 2035 RC, Netherlands

Location

Atrium Medisch Centrum

Heerlen, 6419 PC, Netherlands

Location

Spaarne Ziekenhuis; Inwendige Geneeskunde

Hoofddorp, 2134 TM, Netherlands

Location

Medisch Centrum Leeuwarden; Reumatology

Leeuwarden, 8934 AD, Netherlands

Location

Academisch Ziekenhuis Leiden; Dept of Rheumatology

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Centre; Rheumatology

Maastricht, 6202 ZA, Netherlands

Location

Erasmus Medisch Centrum; Reumatologie

Rotterdam, 3015 CE, Netherlands

Location

Maasstadziekenhuis; Reumatologie

Rotterdam, 3079 DZ, Netherlands

Location

Vlietland Hospital

Schiedam, 3118 JH, Netherlands

Location

Antonius Ziekenhuis Sneek; Department of Rheumatology

Sneek, 8601 ZK, Netherlands

Location

Leyenburg Ziekenhuis; Internal Medecine

The Hague, 2545 CH, Netherlands

Location

St. Bronovo-Nebo

The Hague, 2597 AX, Netherlands

Location

University Medical Centre Utrecht; Reumatologie en Klinische Immunologie

Utrecht, 3584 GA, Netherlands

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: 30649524DERIVED

  • 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: 29244149DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumabMethotrexate

Condition Hierarchy (Ancestors)

ArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic DiseasesConnective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

AminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic 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
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

November 8, 2013

First Posted

November 19, 2013

Study Start

January 30, 2014

Primary Completion

May 26, 2016

Study Completion

May 26, 2016

Last Updated

June 19, 2017

Results First Posted

June 19, 2017

Record last verified: 2017-05

Locations

NL(20)