TOSCARA Study: A Study of Subcutaneous Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis Naïve to RoActemra/Actemra Treatment

NCT02031471 | Completed Phase 3 Results

• 1 other identifier: ML28701
• Study Type: interventional
• Target: 57
• Locations: 2 countries
• Sites: 17

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Full Analysis Set (FAS)

  The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count of 28 joints (TJC28), swollen joint count of 28 joints (SJC28), patient's global assessment of disease activity visual analog scale (PGA VAS) with 0=no disease activity to 100=maximum disease activity displayed on the 100-millimeter (mm) horizontal VAS and acute phase reactant (erythrocyte sedimentation rate \[ESR\] or C-reactive protein \[CRP\]) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56\*√\[TJC28\]) + (0.28\*√\[SJC28\]) + (0.70\*ln\[ESR\]) + (0.014\*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

  From baseline to Week 24

• Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score in the Per Protocol Set (PPS)

  The DAS28 score is a measure of the participant's disease activity calculated using the TJC28, SJC28, PGA VAS with 0=no disease activity to 100=maximum disease activity displayed on the 100-mm horizontal VAS and acute phase reactant (ESR or CRP) for a total possible score of 0 to 10. For this study ESR was used to calculate the DAS28 score. The index is calculated using the following formula: DAS28 = (0.56\*√\[TJC28\]) + (0.28\*√\[SJC28\]) + (0.70\*ln\[ESR\]) + (0.014\*VAS). Higher scores represent higher disease activity. A negative change from baseline indicates an improvement.

  From baseline to Week 24

Secondary Outcomes (25)

• Percentage of Participants With Positive American College of Rheumatology (ACR) Response Scores

  From Baseline to Week 2, Week 24, and Week 52

• Percentage of Participants With Responses According to European League Against Rheumatism (EULAR ) Criteria

  From Baseline to Week 2, Week 24

• Change From Baseline in Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)

  From Baseline to Week 2, Week 24 and Week 52

• Change in Total Tender/Swollen Joint Counts (TJC/SJC)

  From Baseline to Week 2, Week 24 and Week 52

• Percentage of Participants With Corticosteroid Dose Reduction/Discontinuation

  Up to Week 52

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Adults with rheumatoid arthritis received a fixed dose of tocilizumab during the 24-week open-label core study and those entering the long term extension (LTE) period further received a fixed dose up to a maximum of 28 weeks or until tocilizumab was commercially available and/or reimbursed whichever came first. A fixed dose of 162 mg tocilizumab was administered subcutaneously once weekly.

Drug: tocilizumab

Interventions

tocilizumab DRUG

Fixed dose of 162 mg subcutaneously weekly

Also known as: RoActemra/Actemra

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

Unknown Facility

Aalst, 9300, Belgium

Location

Unknown Facility

Assebroek, 8310, Belgium

Location

Unknown Facility

Bonheiden, 2820, Belgium

Location

Unknown Facility

Brussels, 1020, Belgium

Location

Unknown Facility

Brussels, 1050, Belgium

Location

Unknown Facility

Brussels, 1070, Belgium

Location

Unknown Facility

Genk, 3600, Belgium

Location

Unknown Facility

Ghent, 9000, Belgium

Location

Unknown Facility

Gilly (Charleroi), 6000, Belgium

Location

Unknown Facility

Gosselies, 6041, Belgium

Location

Unknown Facility

Haine-Saint-Paul, 7100, Belgium

Location

Unknown Facility

Liège, 4000, Belgium

Location

Unknown Facility

Roeselare, 8800, Belgium

Location

Unknown Facility

Sijsele, 8340, Belgium

Location

Unknown Facility

Sint-Niklaas, 9100, Belgium

Location

Unknown Facility

Wilrijk, 2610, Belgium

Location

Unknown Facility

Luxembourg, 2763, Luxembourg

Location

Related Publications (2)

• 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.

  PMID: 30649524 DERIVED

• 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.

  PMID: 29244149 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: January 9, 2014
• Study Start: January 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: August 1, 2017
• Results First Posted: January 4, 2017

Record last verified: 2017-06

Locations

BE (16); LU (1)