Multicenter, Open Label, Phase IIIb Study to Evaluate the Safety and Tolerability of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Methotrexate or Other Non-Biologic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis
Overview
- Phase
- Phase 3
- Intervention
- Azathioprine
- Conditions
- Rheumatoid Arthritis
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 100
- Locations
- 10
- Primary Endpoint
- Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Azathioprine
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.
Intervention: Chloroquine
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.
Intervention: Hydroxychloroquine
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.
Intervention: Leflunomide
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.
Intervention: Methotrexate
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.
Intervention: Sulfasalazine
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.
Intervention: Tocilizumab
Outcomes
Primary Outcomes
Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24
Time Frame: Week 24
DAS28-ESR score is a measure of participant's disease activity calculated using tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), patient global assessment of disease activity (PGA) (general health \[GH\]) using visual analog scale (VAS): 0 millimeter (mm)=no disease activity to 100 mm=maximum disease activity, displayed on the 100 mm horizontal VAS, and acute phase response (ESR in millimeters per hour \[mm/hr\]). The score is calculated using the following formula: DAS28-ESR = \[0.56 multiplied by (\*) square root (√) of TJC28\] plus (+) \[0.28\*√SJC28\]+\[0.70\*the natural logarithm (ln) ESR\]+\[0.014\*GH\]. DAS28-ESR score varies from 0 to 10, where higher scores represent greater disease activity. DAS28-ESR score of less than (\<) 2.6 represents DAS28-ESR remission.
Secondary Outcomes
- Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24(Weeks 24, 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in SJC28 up to Week 52(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Tocilizumab Serum Levels(Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60))
- Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria(Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in TJC28 up to Week 52(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation(From Baseline up to Week 52)
- PGA, Using VAS Score(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Patient Assessment of Pain, Using VAS Score(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation(From Baseline up to Week 52)
- Number of Participants With Anti-Tocilizumab Antibodies (ATA)(Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60))
- Percentage of Participants Who Received All Planned Study Medication (Compliance)(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- HAQ-DI Score(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Soluble Interleukin-6 Receptor (sIL-6R) Levels(Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60))
- Percentage of Participants Who Achieved DAS28-ESR Remission/Low Disease Activity (LDA) From Week 28 up to Week 52 Among Participants With Intensification of Methotrexate/Other Non-Biologic DMARDs in Combination With Tocilizumab Since Week 24(Weeks 28, 32, 36, 40, 44, 48, 52)
- Change From Baseline in DAS28-ESR up to Week 52(Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)
- Number of Participants With American College of Rheumatology 20 (ACR20) Response(Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52)