Clinical trial NCT01951170: An Open-Label Study of RoActemra/Actemra (Tocilizumab) in Patients With Moderate to Severe Active Rheumatoid Arthritis
Official title: An Open-Label Study to Evaluate Non-Progression Of Structural Joint Damage Of Subcutaneous Tocilizumab In Patients With Moderate To Severe Active Rheumatoid Arthritis (Ac-Cute)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-09-26
Enrollment: 52
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 open-label, single-arm study will evaluate the efficacy and safety of tocilizumab in patients with active moderate to severe rheumatoid arthritis. Participants will receive a subcutaneous dose of tocilizumab 162 mg once weekly. The anticipated time on study treatment is 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Adult patients at least 18 years of age
* Patients with a diagnosis of active moderate to severe rheumatoid arthritis (RA)
* Oral corticosteroids and nonsteroidal anti-inflammatory are permitted if on a stable dose regimen for \>/= 4 weeks prior baseline
* Permitted non-biologic disease-modifying anti-rheumatic drugs (DMARDs) used alone or in combination are allowed if at 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 may participate in this study only if using a reliable means of contraception for at least 5 months following the last dose tocilizumab
* Previous or current treatment with methotrexate with an inadequate response to methotrexate, intolerance to methotrexate or treatment with methotrexate was considered as inappropriate
* Evidence of one or more erosions in hands or feet assessed by X-ray attributable to RA or magnetic resonance imaging (MRI) of wrist of metacarpophalangeal (MCP) joints of dominant hand

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
* Functional Class IV as defined by the American College of Rheumatology (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 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
* Treatment with intravenous (IV) gamma globulin, plasmapheresis within 6 months of baseline
* Intraarticular (IA) or parenteral corticosteroids within 4 weeks prior to baseline
* Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation
* Treatment with 2 or more anti-tumor necrosis factor (TNF) agents or any other biologic agent at any time prior to screening
* Evidence of serious uncontrolled concomitant disease (e.g., cardiovascular, nervous system, pulmonary)
* History of diverticulitis, diverticulosis requiring antibiotic treatment, or chromic ulcerative lower gastrointestinal (GI) disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower genitourinary (GU) conditions that might predispose to perforation
* Known active current or history of recurrent infections

Primary outcomes:
measure: Change From Baseline in Genant-modified Total Sharp Score (mTSS)
timeFrame: From baseline to Week 24
Secondary outcomes:
measure: Percentage of Participants With Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Remission
timeFrame: At Week 24
measure: Percentage of Participants With Positive American College of Rheumatology 20/50/70 (ACR20/50/70) Responses
timeFrame: From baseline to Week 24
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response
timeFrame: From baseline to Week 24
measure: Change From Baseline in Patient's Global Assessment of Disease Activity Visual Analog Scale (PGA VAS)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Patient's Global Assessment of Pain Using a Visual Analog Scale (PGA Pain VAS)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Physician Global Assessment of Disease Activity
timeFrame: From baseline to Week 24
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Simplified Disease Activity Index (SDAI)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Clinical Disease Activity Index (CDAI)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Total Tender Joint Count (TJC)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Swollen Joint Count (SJC)
timeFrame: From baseline to Week 24
measure: Change From Baseline in Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Scoring of Bone Erosions
timeFrame: From baseline to Week 24
measure: Change From Baseline in RAMRIS Scoring of Cartilage Loss
timeFrame: From baseline to Week 24
measure: Change From Baseline in RAMRIS Scoring of Synovitis
timeFrame: From baseline to Week 24
measure: Change From Baseline in RAMRIS Scoring of Osteitis
timeFrame: From baseline to Week 24
measure: Safety: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to Week 32 (end of follow up: 8 weeks after end of treatment)
measure: Safety: Number of AEs Leading to Tocilizumab Dose Modification or Study Treatment Withdrawal
timeFrame: Up to Week 32 (end of follow up: 8 weeks after end of treatment)
measure: Safety: Number of Participants With Confirmed Positive Assessment of Tocilizumab Immunogenicity
timeFrame: At baseline, Week 32 (end of follow up: 8 weeks after end of treatment)
Other outcomes:
Locations:
city: Camperdown
country: Australia
state: New South Wales
city: Coffs Harbour
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Southport
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Geelong
country: Australia
state: Victoria
city: Ivanhoe
country: Australia
state: Victoria
city: Malvern East
country: Australia
state: Victoria
city: Morwell
country: Australia
state: Victoria
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: Bird P, Peterfy C, Countryman P, Griffiths H, Barrett R, Youssef P, Joshua F, Hall S. AC-CUTE: An Open-Label Study to Evaluate Progression of Structural Joint Damage and Inflammation in Subjects with Moderate to Severe Rheumatoid Arthritis. Int J Rheumatol. 2018 Apr 12;2018:8721753. doi: 10.1155/2018/8721753. eCollection 2018.
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.