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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT02573012
Date of registration: 01/10/2015
Prospective Registration: Yes
Primary sponsor: Hoffmann-La Roche
Public title: Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants
Scientific title: Prospective, Multicentre, Placebo-controlled, Double-blind Interventional Study to Compare the Efficacy of Maintenance Treatment With Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Patients
Date of first enrolment: March 29, 2016
Target sample size: 314
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT02573012
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).  
Phase:  Phase 4
Countries of recruitment
Egypt France Germany Italy Russian Federation Serbia Switzerland Tunisia
Turkey
Contacts
Name:     Clinical Trials
Address: 
Telephone:
Email:
Affiliation:  Hoffmann-La Roche
Key inclusion & exclusion criteria

Inclusion Criteria:

Tocilizumab-experienced participants:

- Comply with the requirements of the study protocol (including treatment on an
outpatient basis)

- Rheumatoid arthritis (RA) of greater than or equal to (>=) 6 months duration diagnosed
according to the revised 1987 American College of Rheumatology (ACR) criteria or 2010
ACR / European League Against Rheumatism (EULAR) criteria

- Have received tocilizumab either subcutaneous (162 milligram [mg] once in a week) or
intravenously (8 milligram per kilogram [mg/kg] once every 4 weeks) for the treatment
of RA for at least 24 weeks prior to randomization

- Have received 5 - 15 milligrams per day [mg/day] of glucocorticoids (prednisone or
equivalent) for the treatment of RA for at least 20 weeks prior to screening

- Currently receiving 5 mg/day of prednisone

- Have attained and maintained LDA (DAS28 ESR score <=3.2) or remission (DAS28 ESR score
less than [<] 2.6) for at least 4 weeks prior to randomization

Tocilizumab-naïve participants:

- Comply with the requirements of the study protocol (including treatment on an
outpatient basis)

- RA of >=6 months duration diagnosed according to the revised 1987 ACR criteria or 2010
ACR / EULAR criteria

- Have active RA (defined as DAS28 ESR score greater than [>] 3.2)

- Are considered by the investigator as inadequate responders to conventional synthetic
disease-modifying anti-rheumatic drugs (csDMARDs) or biologic disease-modifying
anti-rheumatic drugs (bDMARDs)

- Are receiving 5 - 15 mg/day prednisone (or equivalent) for the treatment of RA

Exclusion Criteria:

General

- Major surgery (including joint surgery) within 8 weeks prior to screening, or planned
major surgery during the study and up to 6 months after randomization

- Pregnant women or nursing (breastfeeding) mothers

- In females of childbearing potential, a positive serum pregnancy test at screening

- Females of childbearing potential unwilling or unable to use a reliable means of
contraception (for example, physical barrier [participant or partner], contraceptive
pill or patch, spermicide and barrier, or intrauterine device) during study treatment
and for a minimum of 3 months after the last dose of tocilizumab

- Body weight of >=150 kilogram (kg)

- Lack of peripheral venous access

Disease-related

- RA of functional Class 4, as defined by the ACR Classification of Functional Status in
Rheumatoid Arthritis

- Rheumatic autoimmune disease other than RA, including systemic lupus erythematosus,
mixed connective tissue disease, scleroderma, polymyositis, or significant systemic
involvement secondary to RA (for example, vasculitis, pulmonary fibrosis, or Felty
syndrome). Secondary Sjögren syndrome with RA may be allowed per the discretion of the
investigator

- Diagnosed with juvenile idiopathic arthritis or juvenile RA and/or RA before the age
of 16 years

- Prior or current inflammatory joint disease other than RA (for example, gout, Lyme
disease, sero-negative spondyloarthropathy, including reactive arthritis, psoriatic
arthritis, arthropathy of inflammatory bowel disease), or prior or current joint
infections

- Previous history of primary or secondary adrenal insufficiency

Previous or Concomitant Prohibited Therapy

- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
investigational drug, whichever is longer) of screening

- Previous treatment with any cell-depleting therapies, including investigational agents
or approved therapies (for example, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19,
anti-CD20)

- Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6
months of screening

- Intraarticular (IA) or parenteral glucocorticoids for the treatment of RA within 4
weeks prior to screening

- Previous treatment with glucocorticoids for conditions other than RA, at any dose and
in any formulation used continuously for >1 week, during the last 1 year prior to
screening. Topical glucocorticoid creams or ointments for the treatment of skin
conditions (for example eczema) are allowed

- Immunization with a live/attenuated vaccine within 30 days prior to screening.
Participants must agree not to take live attenuated vaccines (including seasonal nasal
flu vaccine, varicella vaccine for shingles or chickenpox, vaccines for measles, mumps
or rubella without or with varicella [MMR or MMRV], oral polio vaccine and vaccines
for yellow fever), within 30 days before the Screening Visit, throughout the duration
of the trial and for 60 days following the last dose of study drug

- Any previous treatment with alkylating agents such as chlorambucil or with total
lymphoid irradiation

Laboratory Exclusion Criteria

- Inadequate haematological, renal and liver function

- Positive hepatitis B surface antigen or hepatitis C antibody Previous or Concomitant
Conditions

- History of severe allergic or anaphylactic reactions to human, humanized, or murine
monoclonal antibodies

- Evidence of current serious uncontrolled cardiovascular (including uncontrolled
hyperlipidemia), nervous system, pulmonary (including obstructive pulmonary disease),
renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or
gastrointestinal (GI) disease

- Current liver disease as determined by the investigator

- History of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic
treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative
colitis, or other symptomatic lower gastrointestinal conditions that might predispose
to perforations

- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial,
or other opportunistic infections (including, but not limited to, tuberculosis [TB]
and atypical mycobacterial disease, hepatitis B and C, Epstein-Barr virus,
cytomegalovirus and herpes zoster, but excluding fungal infections of nail beds)

- Neuropathies or other conditions that might interfere with pain evaluation unless
related to primary disease under investigation

- Any major episode of infection requiring hospitalization or treatment with intravenous
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening

- Active TB requi



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
Intervention(s)
Biological: Tocilizumab
Drug: Placebo matched to prednisone
Drug: Prednisone
Primary Outcome(s)
Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization [Time Frame: Baseline to Week 24]
Secondary Outcome(s)
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 [Time Frame: Baseline and Week 24]
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24 [Time Frame: Randomization to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR) [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Health Assessment Questionnaire-Disability Index (HAQ-DI) [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: High Sensitivity C-Reactive Protein (hsCRP) [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Global Assessment of Disease Activity [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Physician's Global Assessment of Disease Activity [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts [Time Frame: Baseline to Week 24]
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts [Time Frame: Baseline to Week 24]
Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score [Time Frame: Baseline and Week 24]
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score [Time Frame: Baseline and Week 24]
Cumulative Prednisone Exposure (Dose) [Time Frame: Randomization to 24 weeks]
Number of Administrations of Flare Rescue Medication [Time Frame: Randomization to 24 weeks]
Percentage of Participants Who Maintain LDA (DAS28 ESR Score <=3.2) or Remission (DAS28 ESR Score <2.6) and the Percentage of Participants Who Maintain the Baseline Disease Activity Level [Time Frame: Randomization to Week 24]
Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control [Time Frame: 24 weeks]
Percentage of Participants With >=1 Administration of Flare Rescue Medication [Time Frame: Randomization to 24 weeks]
Percentage of Participants With >=1 Flare [Time Frame: 24 weeks]
Percentage of Visits With RA Flares [Time Frame: Randomization to 24 weeks]
Time to First Administration of Flare Rescue Medication [Time Frame: Randomization to 24 weeks]
Time to First RA Flare [Time Frame: Randomization to 24 weeks]
Treatment Success [Time Frame: Week 24]
Secondary ID(s)
2014-004673-16
MA29585
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available: Yes
Date Posted: 24/07/2019
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT02573012
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