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

Roche

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Drug: Hydroxychloroquine; Drug: Tocilizumab; Drug: Chloroquine; Drug: Leflunomide; Drug: Sulfasalazine; Drug: Azathioprine; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT01941095

2013-000359-42 (EudraCT Number)

ML28695

Details and patient eligibility

About

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.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Tocilizumab

Experimental group

Description:

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.

Treatment:

Drug: Azathioprine

Drug: Sulfasalazine

Drug: Chloroquine

Drug: Leflunomide

Drug: Hydroxychloroquine

Drug: Tocilizumab

Drug: Methotrexate