Clinical Trials/NCT01995201

NCT01995201

Completed

Phase 3

A Phase IIIb Study to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous (SC) Tocilizumab (TCZ) Given as Monotherapy or in Combination With Methotrexate (MTX) or Other Non Biologics DMARDs in Subjects With Rheumatoid Arthritis

Hoffmann-La Roche0 sites401 target enrollmentSeptember 2013

ConditionsRheumatoid Arthritis

InterventionsDMARD methotrexate tocilizumab [RoActemra/Actemra]

DrugsDMARD methotrexate tocilizumab [RoActemra/Actemra]

Overview

Phase: Phase 3
Intervention: DMARD
Conditions: Rheumatoid Arthritis
Sponsor: Hoffmann-La Roche
Enrollment: 401
Primary Endpoint: Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This multicenter, open-label study will evaluate the efficacy and safety of subcutaneously administered RoActemra/Actemra (tocilizumab) as monotherapy or in combination with methotrexate or other non-biologic DMARDs in patients with active rheumatoid arthritis and an inadequate response to non-biologic DMARDs or to one anti-TNF. In Phase 1, all patients will receive RoActemra/Actemra 162 mg subcutaneously (sc) weekly for Weeks 1 to 24, with or without methotrexate or other non-biologic DMARDs. For Part 2, patients who achieve sustained clinical DAS28-ESR remission at Weeks 20 and 24 will be randomized to receive RoActemra/Actemra 162 mg sc either weekly or every 2 weeks for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs. Patients who do not achieve sustained clinical remission but achieve low disease activity (DAS-ESR </= 3.2) will continue the initial treatment of RoActemra/Actemra 162 mg sc weekly for Weeks 24 to 48, with or without methotrexate or other non-biologic DMARDs.

Registry

clinicaltrials.gov

Start Date

September 2013

End Date

March 2016

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Adult patients, \>/= 18 years of age
•Active rheumatoid arthritis (DAS28-ESR \> 3.2), according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria of \> 6 months duration
•Patients with intolerance or inadequate response to methotrexate or other non-biologic DMRADs or inadequate response to a first ant-TNF agent
•Oral corticosteroids (\</= 10 mg/day prednisone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for \>/= 4 weeks prior to baseline
•Permitted non-biologic DMRAD is allowed if at stable dose for at least 4 weeks prior to baseline
•Females of childbearing potential and males with female partners of childbearing potential must be using a reliable means of contraception as defined by protocol during the study and for at least 3 months following the last dose of RoActemra/Actemra
•Patients with intolerance or inadequate response to methotrexate or other non-biologic DMARDs or inadequate response to first anti-TNF agent

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 or significant systemic involvement secondary to RA; secondary Sjögren's syndrome with RA is permitted
•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 current inflammatory joint disease other than RA
•Exposure to tocilizumab (either intravenous \[IV\] or SC) at any time prior to baseline
•Treatment with any investigational agent with four weeks (or five-half lives of the investigational drug, whichever is longer) of screening
•Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
•Previous treatment with Abatacept
•History of severe allergic of anaphylactic reactions to human, humanized, or murine monoclonal antibodies

Arms & Interventions

Part 1: All patients

Intervention: DMARD

Part 1: All patients

Intervention: methotrexate

Part 1: All patients

Intervention: tocilizumab [RoActemra/Actemra]

Part 2 A: Sustained clinical remission

Intervention: DMARD

Part 2 A: Sustained clinical remission

Intervention: methotrexate

Part 2 A: Sustained clinical remission

Intervention: tocilizumab [RoActemra/Actemra]

Part 2 B: Low disease activity

Intervention: DMARD

Part 2 B: Low disease activity

Intervention: methotrexate

Part 2 B: Low disease activity

Intervention: tocilizumab [RoActemra/Actemra]

Outcomes

Primary Outcomes

Percentage of Participants Achieving Sustained Clinical Remission, Disease Activity Scale 28 - Erythrocyte Sedimentation Rate <26 (DAS28-ESR <2.6) at Week 20 and Week 24

Time Frame: Week 20 and Week 24

The DAS 28 is a combined index for measuring disease activity in RA. The index includes the assessment of 28 joints for swelling and tenderness, acute phase response (ESR or CRP) and general health status. For this study ESR was used to calculate the DAS 28 score.

Secondary Outcomes

Percentage of Patients Reporting Change in DAS 28 ESR >1.2 Until Week 48(From week 28 up to week 48)
Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 48(From week 24 until week 48)
Percentages of Patients Who Achieve DAS28-ESR Remission (DAS28 < 2.6) up to Week 48(Week 48)
Percentages of Patients With Remission (CDAI<2.8) Until Week 24(From baseline to Week 24)
Number of Patients With Good and Moderate Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 24(From week 2 until week 24)
Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 48(From week 28 until week 48)
Number of Patients With Clinical Response According to European League Against Rheumatism (EULAR) Response Scores up to Week 48(From week 28 until week 48)
Mean Change in Simplified Disease Activity Index (SDAI) From Baseline up to Week 24(From baseline to Week 24)
Mean Change in Simplified Disease Activity Index (SDAI) From Week 24 up to Week 48(From week 24 until week 48)
Mean Change From Baseline in Total Tender Joint Counts (TJC) Until Week 24(From baseline to Week 24)
Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 24(From baseline to Week 24)
Mean Change in Disease Activity Score 28 - Erythrocyte Sedimentation Rate(DAS28-ESR)(From week 24 up to week 48)
Percentage of Patients With American College of Rheumatology (ACR20, 50, 70, 90) Response Scores Until Week 24(From week 2 until week 24)
Percentage of Patients Allocated in Groups A1 and A2 Who Remain With Clinical Remission Activity (DAS 28 ESR <2.6) up to Week 48(From week 28 up to week 48)
Mean Change in Clinical Disease Activity Index (CDAI) From Baseline up to Week 24(From baseline to Week 24)
Mean Change From Baseline in Clinical Disease Activity Index (CDAI) up to Week 48(From week 24 until week 48)
Percentages of Patients With Remission (CDAI<2.8) Until Week 48(From week 28 until week 48)
Mean Change in Total Swollen Joint Counts (SJC) From Baseline Until Week 48(From week 24 until week 48)
Percentages of Patients With Remission (SDAI<3.3) Until Week 24(From baseline to Week 24)
Percentages of Patients With Remission (SDAI<3.3) Until Week 48(From week 28 until week 48)
Immunogenicity: SIL-6R Levels up to Week 24(From baseline to Week 24)
Immunogenicity: SIL-6R Levels at Week 36 and Early Withdrawal Visit(Baseline, Week 36 and Early Withdrawal Visit)
Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 24(From baseline to Week 24)
Percentage of Patients Who Achieve Low Disease Activity Based on DAS28-ESR Criteria (DAS28-ESR </=3.2) up to Week 48(From week 28 until week 48)
Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 48(From week 28 until week 48)
Safety: Number of Patients Reporting Adverse Events up to Week 48(From week 24 until week 48)
Percentage of Patients Who Achieve Low Disease Activity Based on CDAI Score (CDAI<10) Until Week 24(From baseline to Week 24)
Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 24(From baseline to Week 24)
Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 24(From baseline to Week 24)
Immunogenicity: Number of Patients With Anti-tocilizumab Antibodies up to Week 48(From week 24 until week 48)
Immunogenicity: TCZ Levels at Week 36 and Early Withdrawal Visit(week 36 and early withdrawal visit)
Percentage of Patients Who Achieved Low Disease Activity (LDA) Based on SDAI Score (SDAI<11) Until Week 48(From week 28 until week 48)
Safety: Number of Patients Reporting Adverse Events up to Week 24(From baseline to Week 24)
Immunogenicity: TCZ Levels up to Week 24(From baseline to Week 24)
Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 24(From baseline to Week 24)
Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 24(From baseline to Week 24)
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 48(Baseline, from week 28 until week 48)
Patient Global Assessment of Disease Activity Visual Analogue Scale (VAS) up to Week 48(Baseline, from week 28 until week 48)
Assessment of Pain Reported by the Patient (VAS) Until Week 48(Baseline, from week 28 until week 48)
Assessment of Pain Reported by the Patient (VAS) Until Week 24(From baseline to Week 24)
Health Assessment Questionnaire-Disability Index (HAQ-DI) up to Week 48(Baseline, from week 28 until week 48)
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) up to Week 24(From baseline to Week 24)