Clinical trial NCT01987479: A Study on Safety and Efficacy of Tocilizumab (RoActemra/Actemra) Alone or in Combination With Non-Biologic Antirheumatics in Participants With Rheumatoid Arthritis
Official title: Multi-Center, Open Label, Single Arm Phase IIIB Study on Safety and Efficacy of Subcutaneous Tocilizumab in Monotherapy or in Combination With Methotrexate or Other Non-Biologic Disease Modifying Antirheumatic Drugs in Rheumatoid Arthritis Patients With an Inadequate Response to Non-Biologic DMARDs - OSCAR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-19
Enrollment: 150
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 multi-center, open-label single arm Phase IIIb study will evaluate the safety and efficacy of subcutaneous (SC) tocilizumab administered as monotherapy and/or in combination with methotrexate or other non-biologic disease modifying antirheumatic drugs (DMARDs) in participants with rheumatoid arthritis (RA) with an inadequate response to non-biologic DMARDs.


Eligibility criteria: Inclusion Criteria:

* Participants with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
* Oral corticosteroids (≤10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for greater than or equal to (≥\]) 4 weeks prior to Baseline.
* Use of effective contraception throughout the study as defined by protocol; female participants of childbearing potential cannot be pregnant.

Exclusion Criteria:

* Presence of clinically significant medical conditions.
* History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease that might predispose to perforation.
* Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
* Any infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
* Clinically significant findings on laboratory tests.
* Positive hepatitis B surface antigen or hepatitis C antibody.
* Active tuberculosis requiring treatment within the previous 3 years.
* Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
* History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
* Neuropathies or other conditions that might interfere with pain evaluation.
* 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, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted.
* Functional Class IV as defined by the ACR Classification of Functional Status in RA.
* Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16 years.
* Prior history of or current inflammatory joint disease other than RA.
* Exposure to tocilizumab (either intravenous 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-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
* Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
* Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

Primary outcomes:
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to Week 32
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants Achieving an American College of Rheumatology Criteria 20 (ACR20) Response
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants Achieving an ACR50 Response
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants Achieving an ACR70 Response
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants Achieving an ACR90 Response
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response (Good, Moderate or No Response) Based on DAS28-ESR
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 16, 20, 24, and Early Withdrawal
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Change From Baseline in Total TJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Change From Baseline in Total SJC at Weeks 2, 4, 8, 12, 16, 20, 24, and Early Withdrawal
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and at Early Withdrawal (up to Week 24)
measure: Percentage of Participants With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Dose Reductions or Discontinuation Categorized by Reasons
timeFrame: From Week 16 and before Week 20; From Week 20 and before Week 24
measure: Percentage of Participants With Corticosteroid Dose Reductions or Discontinuation Categorized by Reasons
timeFrame: From Week 16 and before Week 20; From Week 20 and before Week 24
measure: Time to Discontinuation or First Dose Reduction of Corticosteroids or NSAIDs
timeFrame: Baseline up to Week 32
measure: Percentage of Participants With Anti-Tocilizumab Antibodies
timeFrame: Baseline, Weeks 12 and 24, early withdrawal (up to Week 24), follow-up visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
measure: Serum Levels of Tocilizumab
timeFrame: Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
measure: Serum Levels of Soluble Interleukin-6 Receptors (sIL-6Rs)
timeFrame: Baseline, Weeks 12 and 24, Early Withdrawal (up to Week 24), Follow-up Visit (8 weeks after last dose of tocilizumab, up to 32 weeks)
measure: Patient Global Assessment of Disease Activity VAS Scores
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)
measure: Patient Pain VAS Scores
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and Early withdrawal (up to Week 24)
measure: Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
measure: Percentage of Participants Compliant to Tocilizumab Treatment as Measured by Diary Cards and Return Records
timeFrame: Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
measure: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
timeFrame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, and early withdrawal (up to Week 24)
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: ZGT Almelo; Reumatologie
city: Amsterdam
country: Netherlands
facility: Jan Van Breemen Instituut
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen; Reumatologie
city: Breda
country: Netherlands
facility: Amphia ziekenhuis, locatie langendijk
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis ; Dordwijk
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen; Department of Rheumatology
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis
city: Heerlen
country: Netherlands
facility: Atrium Medisch Centrum
city: Hoofddorp
country: Netherlands
facility: Spaarne Ziekenhuis; Inwendige Geneeskunde
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden; Reumatology
city: Leiden
country: Netherlands
facility: Academisch Ziekenhuis Leiden; Dept of Rheumatology
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre; Rheumatology
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum; Reumatologie
city: Rotterdam
country: Netherlands
facility: Maasstadziekenhuis; Reumatologie
city: Schiedam
country: Netherlands
facility: Vlietland Hospital
city: Sneek
country: Netherlands
facility: Antonius Ziekenhuis Sneek; Department of Rheumatology
city: The Hague
country: Netherlands
facility: Leyenburg Ziekenhuis; Internal Medecine
city: The Hague
country: Netherlands
facility: St. Bronovo-Nebo
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht; Reumatologie en Klinische Immunologie
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.