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

NCT01941095 | Completed Phase 3 Results

• 2 other identifiers: ML286952013-000359-42
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at 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.

  Week 24

Secondary Outcomes (18)

• 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

• 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

• 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

Study Arms (1)

Tocilizumab

EXPERIMENTAL

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.

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

Interventions

Azathioprine DRUG

Participants may receive azathioprine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Chloroquine DRUG

Participants may receive chloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Hydroxychloroquine DRUG

Participants may receive hydroxychloroquine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Leflunomide DRUG

Participants may receive leflunomide as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Methotrexate DRUG

Participants may receive methotrexate as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Sulfasalazine DRUG

Participants may receive sulfasalazine as a concomitant therapy with tocilizumab as per physician's judgment at a stable dose that was initiated at least 4 weeks prior to baseline.

Tocilizumab

Tocilizumab DRUG

Participants will receive tocilizumab at a fixed dose of 162 mg SC QW either as monotherapy or in combination with non-biologic DMARDs.

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:

• 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

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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (10)

District Gen. Hosp. of Athens Laiko; A Propedeutic Internal Medicine Clinic & Research Center

Athens, 115 27, Greece

Location

Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens

Athens, 115 27, Greece

Location

Hippokratio Hospital; 2Nd Internal Medicine

Athens, 11527, Greece

Location

ATTIKO Hospital_4th University Internal Medicine Clinic

Haidari, 124 62, Greece

Location

Uni General Hospital of Heraklion; Medicine and Rheumatology Clinical Immunology and Allergy Dept

Heraklion, 711 10, Greece

Location

Uni Hospital of Ioannina; Rheumatology

Ioannina, 455 00, Greece

Location

University General Hospital of Larissa; Rheumatology Unit

Larissa, 411 10, Greece

Location

University Hospital of Patras; Rheumatology

Pátrai, 265 04, Greece

Location

EUROMEDICA Geniki Kliniki Thessalonikis; Rheumatology Department

Thessaloniki, 544 65, Greece

Location

General Hospital of Thessaloniki HIPPOKRATIO; Clinical Immunology Unit,2nd Dept of Internal Medicine

Thessaloniki, 546 42, Greece

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

Azathioprine; Chloroquine; Hydroxychloroquine; Leflunomide; Methotrexate; Sulfasalazine; tocilizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminoquinolines; Quinolines; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines; Sulfonamides; Amides; Sulfones

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: August 30, 2013
• First Posted: September 13, 2013
• Study Start: November 20, 2013
• Primary Completion: July 10, 2016
• Study Completion: July 10, 2016
• Last Updated: November 13, 2018
• Results First Posted: November 13, 2018

Record last verified: 2018-04

Locations

GR (10)