Clinical trial NCT01988012: A Study of the Efficacy and Safety of Tocilizumab in Adults With Rheumatoid Arthritis.
Official title: An Open-label, Multicenter Study to Evaluate Disease Activity and Safety of Treatment With Actemra (Tocilizumab) Administered as Subcutaneous Injection in Adult RA Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-20
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: A multi-center, open-label single-arm study to evaluate the efficacy and safety of tocilizumab administered as a single, weekly injection in adults with rheumatoid arthritis. Combination therapy with methotrexate or other non-biologic disease modifying anti-rheumatic drugs (DMARDs) was permitted.


Eligibility criteria: Inclusion Criteria:

* Adults \>/= 18 years of age
* Diagnosis of active rheumatoid arthritis (RA) according to the revised (1987) American College of Rheumatology (ACR) criteria or European League Against Rheumatism (EULAR)/ACR (2010) criteria
* Previously treated with the following: three non-biologic DMARDs, and not treated with any biologic agent OR one biologic agent (alone or in combination with non-biologic DMARDs), and discontinued that agent for a reason
* Oral corticosteroids (\</= 10 mg/day prednisone or equivalent), non-steroidal anti-inflammatory drug (NSAIDs) and non-biologic DMARDs are permitted if on a stable dose regimen for \>/= 4 weeks prior to Baseline
* Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential must not be pregnant

Exclusion Criteria:

* Presence of serious, uncontrolled, clinically significant medical conditions
* History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal (GI) 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 (IV) antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
* Clinically significant findings on lab tests and/or hepatitis B or C, or human immunodeficiency virus (HIV) screenings
* Active tuberculosis (TB) requiring treatments 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 erythematosus, 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-Rheumatoid Arthritis
* Diagnosis of juvenile idiopathic arthritis or juvenile RA, and/or RA before the age of 16
* Prior history of current inflammatory joint disease other than RA
* Exposure to tocilizumab (either IV or subcutaneous administration) 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 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 Clinical Disease Activity Index (CDAI) Remission and CDAI Low Disease Activity
timeFrame: Week 24
measure: Change From Baseline in CDAI
timeFrame: Baseline, Week 24
measure: Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission and SDAI Low Disease Activity
timeFrame: Week 24
measure: Change From Baseline in SDAI
timeFrame: Baseline, Week 24
measure: Change From Baseline in Disease Activity Score 28-Erythrocyte-Sedimentation Rate (DAS28-ESR)
timeFrame: Baseline, Week 24
measure: Percentage of Participants Achieving 20%, 50% and 70% Improvement in American College of Rheumatology (ACR) Response Scores (ACR20, ACR50 and ACR70)
timeFrame: Week 24
measure: Percentage of Participants With Good to Moderate European League Against Rheumatism (EULAR) Response
timeFrame: Week 24
measure: Change From Baseline in TJC and SJC
timeFrame: Baseline, Week 24
measure: Change From Baseline in Percentage of Participants on Tocilizumab Monotherapy
timeFrame: Baseline, Week 24
measure: Change From Baseline in Patient Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Patient Pain VAS
timeFrame: Baseline, Week 24
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Patient Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: Baseline, Week 24
measure: Total Scores on Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS)
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and AEs of Special Interest (AESIs)
timeFrame: Up to Follow-up Week 32
measure: Percentage of Participants Who Required Dose Modifications or Discontinued Study Due to AEs
timeFrame: Up to Week 24
measure: Immunogenicity: Percentage of Participants With Anti-tocilizumab Antibodies
timeFrame: Baseline, Week 24, Follow-up Week 32 and Early Withdrawal
measure: Immunogenicity: Tocilizumab Levels
timeFrame: Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
measure: Immunogenicity: Change From Week 1 in Soluble Interleukin-6 Receptor (sIL-6R) Levels
timeFrame: Week 1, Week 12, Week 24, Follow-up Week 32 and Early Withdrawal
Other outcomes:
Locations:
city: Beer Sheva
country: Israel
city: Beer Yaacov
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petach Tikva
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
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.