A Study of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Non-Biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) in Participants With Rheumatoid Arthritis

NCT ID: NCT01941095

Last Updated: 2018-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-20
• Study Completion Date: 2016-07-10

Brief Summary

This Phase IIIb, multicenter, open label, single arm study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab as monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active rheumatoid arthritis who are either naïve to or have an inadequate response to prior non-biologic or/and biologic DMARDs. The anticipated time on study treatment is 52 weeks. Those participants who will complete the 60-week study period and have achieved Disease Activity Score 28 (DAS28) remission or a good European League Against Rheumatism (EULAR) response at 52 weeks will be eligible to enter the extension phase until tocilizumab is commercially available and reimbursed in Greece.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab

Participants will receive tocilizumab 162 milligrams (mg) SC injection once a week (QW) either as monotherapy or in combination with methotrexate or other non-biologic DMARDs during the treatment period of 52 weeks. The choice of monotherapy or combination treatment is according to the physician's judgment up to Week 24. Depending upon the participant's response to study regimen at Week 24, participant may either continue/discontinue/switch to tocilizumab monotherapy or may lead to intensification of methotrexate/non-biologic DMARDs with tocilizumab at a fixed dose of 162 mg SC QW till Week 52. After Week 52, participants who remain in study will enter a 8 week wash-out period and then (from Week 60) will proceed to the extension phase until tocilizumab is commercially available in Greece. Permitted DMARDs include methotrexate, azathioprine, chloroquine, hydroxychloroquine, leflunomide, and sulfasalazine.

Group Type: EXPERIMENTAL

Azathioprine

Intervention Type: DRUG

Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Chloroquine

Intervention Type: DRUG

Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Hydroxychloroquine

Intervention Type: DRUG

Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Leflunomide

Intervention Type: DRUG

Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Methotrexate

Intervention Type: DRUG

Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Sulfasalazine

Intervention Type: DRUG

Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Intervention Type: DRUG

Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.

Interventions

Azathioprine

Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Chloroquine

Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Hydroxychloroquine

Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Leflunomide

Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Methotrexate

Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Sulfasalazine

Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Intervention Type: DRUG

Tocilizumab

Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.

Intervention Type: DRUG

Other Intervention Names

RoActemra, Actemra

Eligibility Criteria

Inclusion Criteria

• Diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria
• Oral corticosteroids (less than or equal to [</=] 10 milligrams per day [mg/day] prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for greater than or equal to [>/=] 4 weeks prior to baseline
• Permitted non biologic DMARDs are allowed if a 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 a reliable means of contraception during the study; females of childbearing potential must use a reliable means of contraception for at least 3 month 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 rheumatoid arthritis; secondary Sjögren's syndrome with rheumatoid arthritis is permitted
• Functional Class 4 as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
• Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16
• Prior history of or current inflammatory joint disease other than rheumatoid arthritis
• Participants with lack of peripheral venous access
• Exposure to tocilizumab (either intravenous [IV] or SC) at any time prior to baseline
• Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of screening
• Previous treatment with any cell-depending therapies
• Treatment with IV gamma globulin, plasmapheresis within 6 months of baseline
• Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
• Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
• Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
• 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 of 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
• Primary or secondary immunodeficiency (history of or currently active)
• Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
• Pregnant or breast feeding women
• History of alcohol, drug or chemical abuse within 1 year prior to screening
• Neuropathies or other conditions that interfere with pain evaluation

• 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

District Gen. Hosp. of Athens Laiko; A Propedeutic Internal Medicine Clinic & Research Center

Athens, , Greece

Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens

Athens, , Greece

Hippokratio Hospital; 2Nd Internal Medicine

Athens, , Greece

ATTIKO Hospital_4th University Internal Medicine Clinic

Haidari, , Greece

Uni General Hospital of Heraklion; Medicine and Rheumatology Clinical Immunology and Allergy Dept

Heraklion, , Greece

Uni Hospital of Ioannina; Rheumatology

Ioannina, , Greece

University General Hospital of Larissa; Rheumatology Unit

Larissa, , Greece

University Hospital of Patras; Rheumatology

Pátrai, , Greece

EUROMEDICA Geniki Kliniki Thessalonikis; Rheumatology Department

Thessaloniki, , Greece

General Hospital of Thessaloniki HIPPOKRATIO; Clinical Immunology Unit,2nd Dept of Internal Medicine

Thessaloniki, , Greece

Countries

Greece

References

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

2013-000359-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML28695

Identifier Type: -

Identifier Source: org_study_id