Clinical trial NCT01941095: 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
Official title: Multicenter, Open Label, Phase IIIb Study to Evaluate the Safety and Tolerability of Subcutaneous Tocilizumab as Monotherapy and/or in Combination With Methotrexate or Other Non-Biologic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-09-13
Enrollment: 100
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 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.


Eligibility criteria: Inclusion Criteria:

* 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

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 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
* Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
* Any major episode of infection requiring hospitalization of 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 surface antigen or hepatitis C antibody
* Primary or secondary immunodeficiency (history of or currently active)
* Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (except for basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years
* Pregnant or breast feeding women
* History of alcohol, drug or chemical abuse within 1 year prior to screening
* Neuropathies or other conditions that interfere with pain evaluation

Primary outcomes:
measure: Percentage of Participants Who Achieved Disease Activity Score Based on 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR) Remission at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Who Maintained DAS28-ESR Remission From Week 24 up to Week 52 Among Participants on Tocilizumab Monotherapy Since Week 24
timeFrame: Weeks 24, 28, 32, 36, 40, 44, 48, 52
measure: 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
timeFrame: Weeks 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in DAS28-ESR up to Week 52
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Number of Participants With American College of Rheumatology 20 (ACR20) Response
timeFrame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Response Criteria
timeFrame: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) Score up to Week 52
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in TJC28 up to Week 52
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Change From Baseline in SJC28 up to Week 52
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Percentage of Participants With Corticosteroid Dose Reduction or Discontinuation
timeFrame: From Baseline up to Week 52
measure: Number of Participants by Reasons (Categories) for Corticosteroid Dose Reduction or Discontinuation
timeFrame: From Baseline up to Week 52
measure: Number of Participants With Anti-Tocilizumab Antibodies (ATA)
timeFrame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
measure: Soluble Interleukin-6 Receptor (sIL-6R) Levels
timeFrame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
measure: Tocilizumab Serum Levels
timeFrame: Baseline (Week 1), Weeks 12, 24, 36, 52, and 8 weeks after Week 52 dose (Week 60)
measure: PGA, Using VAS Score
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Patient Assessment of Pain, Using VAS Score
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: HAQ-DI Score
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Percentage of Participants Who Received All Planned Study Medication (Compliance)
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
measure: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
timeFrame: Baseline (Week 1), Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Other outcomes:
Locations:
city: Athens
country: Greece
facility: District Gen. Hosp. of Athens Laiko; A Propedeutic Internal Medicine Clinic & Research Center
city: Athens
country: Greece
facility: Laiko General Hospital; Dept. of Pathophysiology-Uni of Athens
city: Athens
country: Greece
facility: Hippokratio Hospital; 2Nd Internal Medicine
city: Haidari
country: Greece
facility: ATTIKO Hospital_4th University Internal Medicine Clinic
city: Heraklion
country: Greece
facility: Uni General Hospital of Heraklion; Medicine and Rheumatology Clinical Immunology and Allergy Dept
city: Ioannina
country: Greece
facility: Uni Hospital of Ioannina; Rheumatology
city: Larissa
country: Greece
facility: University General Hospital of Larissa; Rheumatology Unit
city: Patras
country: Greece
facility: University Hospital of Patras; Rheumatology
city: Thessaloniki
country: Greece
facility: EUROMEDICA Geniki Kliniki Thessalonikis; Rheumatology Department
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki HIPPOKRATIO; Clinical Immunology Unit,2nd Dept of Internal Medicine
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.