Clinical trial NCT02031471: TOSCARA Study: A Study of Subcutaneous Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis Naïve to RoActemra/Actemra Treatment
Official title: TOSCARA: An Open-label, Single Arm Study to Evaluate the Efficacy, Safety and Tolerability of Tocilizumab (TCZ) Subcutaneous in TCZ-naïve Patients With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-01-09
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single-arm study will evaluate the efficacy, safety and tolerability of subcutaneously administered tocilizumab in monotherapy and/or in combination with methotrexate and other non-biologic disease modifying anti-rheumatic drug (DMARDs) in participants with active rheumatoid arthritis (RA) who are naïve to tocilizumab. Participants will receive tocilizumab 162 milligram (mg) subcutaneously weekly for 24 weeks. Participants who complete the core study achieving at least a moderate European League Against Rheumatism (EULAR) response at Week 24 may enter the extension phase and receive for a further 28 weeks at the most.


Eligibility criteria: Inclusion Criteria:

* Adult participants, \>/= 18 years of age
* Active moderate to severe rheumatoid arthritis according to the revised (1987) American College of Rheumatology (ACR) criteria or EULAR/ACR (2010) criteria
* Inadequate response or intolerant to previous therapy with two or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of which is methotrexate, administered in an optimal way during at least 3 months; eligible participants may also be inadequate responders to a maximum of one biologic DMARD
* Oral corticosteroids (\</= 10 milligram per day (mg/day) prednisolone or equivalent) and non-steroidal anti-inflammatory drugs (NSAIDs; up to the recommended dose) are permitted if on stable dose regimen for \>/= 4 weeks prior to baseline
* Permitted DMARDs are allowed if at 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 reliable means of contraception as defined by protocol

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline or during long term extension (LTE) period
* Rheumatic autoimmune disease other than rheumatoid arthritis
* 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 or current inflammatory joint disease other than RA
* Exposure to tocilizumab (intravenous or subcutaneous) at any time prior to baseline
* Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
* Intraarticular or parenteral corticosteroids within 4 weeks prior to baseline
* History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
* Evidence of serious concomitant disease or disorder
* Known active current or history of recurrent infection
* Any major episode of infection requiring hospitalization or 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 or hepatitis C
* Primary or secondary immunodeficiency (history of or currently active)
* Pregnant or lactating women
* Neuropathies or other conditions that might interfere with pain evaluation
* Inadequate hematologic, renal or liver function

Primary outcomes:
measure: Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS)
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores
timeFrame: From Baseline to Week 2, Week 24, and Week 52
measure: Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria
timeFrame: From Baseline to Week 2, Week 24
measure: Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change in Total Tender/Swollen Joint Counts (TJC/SJC)
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation
timeFrame: Up to Week 52
measure: Percentage of Participants Achieving CDAI Remission, CDAI Low Disease Activity, Moderate Disease Activity and High Disease Activity
timeFrame: Baseline to Week 2, Week 24 and Week 52
measure: Percentage of Participants Achieving SDAI Remission, SDAI LDA, Moderate Disease Activity and High Disease Activity
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Percentage of Participants Achieving DAS28-ESR Remission, DAS28-ESR LDA, Moderate Disease Activity and High Disease Activity
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Percentage of Participants Achieving a Clinically Significant Improvement in DAS28
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Physician's Global Assessment of Disease Activity VAS
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Patient's Global Assessment of Disease Activity VAS
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Patient's Assessment of Pain VAS
timeFrame: From Baseline to Week 2 and Week 24
measure: Acute Phase Reactants: Change From Baseline in CRP
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Acute Phase Reactants: Change From Baseline in ESR
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI)
timeFrame: From Baseline to Week 4, Week 24 and Week 52
measure: Change From Baseline in Patient Quality of Sleep VAS
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Arthritis Impact Measurement Scale-Short Form (AIMS-SF)
timeFrame: From Baseline to Week 4, Week 24 and Week 52
measure: Change From Baseline in Patient Fatigue VAS
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Patient Satisfaction VAS
timeFrame: From Baseline to Week 2, Week 24 and Week 52
measure: Change From Baseline in Work Instability Scale for Rheumatoid Arthritis (RA-WIS)
timeFrame: From Baseline to Week 24
measure: Treatment Satisfaction Questionnaire for Medication (TSQM ) Scores
timeFrame: Week 24
measure: Safety: Percentage of Participants With Adverse Events
timeFrame: Up to 52 weeks
measure: Safety: Percentage of Participants With Anti-tocilizumab Antibodies
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Aalst
country: Belgium
city: Assebroek
country: Belgium
city: Bonheiden
country: Belgium
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Gilly (Charleroi)
country: Belgium
city: Gosselies
country: Belgium
city: Haine-Saint-Paul
country: Belgium
city: Liège
country: Belgium
city: Roeselare
country: Belgium
city: Sijsele
country: Belgium
city: Sint-Niklaas
country: Belgium
city: Wilrijk
country: Belgium
city: Luxembourg
country: Luxembourg
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.