Rheumatoid ArthritisPhase 4NCT02573012
Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants
A Phase 4 study testing Prednisone and Tocilizumab in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 39 sites in 6 countries.
Trial summary
This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial compares the change in disease activity (as assessed by Disease Activity Score in 28 joints [DAS28] erythrocyte sedimentation rate [ESR]) from randomization to Week 24 post-randomization, in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Prednisone and Tocilizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 314 participants
- Where
- 39 sitesin 6 countries
- Study dates
- 29 Mar 2016to 9 Feb 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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)
Show all 37Show fewer
- 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 requiring treatment within the previous 3 years (participants previously treated for TB with no recurrence within 3 years are permitted). All Track tocilizumab-naïve participants must be screened for latent TB and if positive, should be treated following local practice guidelines prior to initiating tocilizumab
- History of or currently active, primary or secondary immunodeficiency
- Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including haematological malignancies and solid tumours, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that was excised and cured), or breast cancer diagnosed within the previous 20 years
- History of alcohol, drug or chemical abuse within 1 year prior to screening
- Pre-existing central nervous system (CNS) demyelination or seizure disorders
- Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
Trial locations and contacts
39 sites in 6 countries.
39 sites in 6 countries
Germany20 sites
Praxis Dr. med. Reiner Kurthen
Aachen, 52064
Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
Bad Abbach, 93077
Rheumatologische Gemeinschaftspraxis Grafschaft, Dr. med. Dorothea Pick, Dr. med. Christopher Amberg
Bad Neuenahr-Ahrweiler, 53474
Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie
Berlin, 10117
SchlossPark-Klinik Berlin; Int. Med. II, Rheum. Osteo
Berlin, 14059
Klinik der Uni zu Köln; Klinik für Innere Medizin
Cologne, 50924
Rheumatologisches MVZ Dresden GmbH, Dres. Holger Schwenke, Reiner Schwenke, Annekatrin Georgi
Dresden, 01109
MVZ Ambulantes Rheumazentrum
Erfurt, 99096
Dres. Florian Schuch, Ruediger de la Camp, Martin Hammerschmidt u.w.
Erlangen, 91056
Universitätsklinikum Hamburg-Eppendorf Zentrum f.Innere Medizin Med.Klinik III
Hamburg, 20246
Praxis Dr.med. Maria Höhle
Hamburg, 22147
Rheumapraxis PD Dr.med. Bernhard Heilig
Heidelberg, 69120
Rheumatologische Facharztpraxis Maren Sieburg
Magdeburg, 39104
SMO.MD GmbH, Zentrum für klinische Studien
Magdeburg, 39120
Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
München, 80336
Praxiszentrum St. Bonifatius
München, 81541
Rheumapraxis an der Hase
Osnabrück, 49074
Rheumazentrum Ratingen - Studienambulanz
Ratingen, 40878
Rheumatologische Schwerpunktpraxis am Feuersee
Stuttgart, 70178
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Rheumatologie/Immunologie
Würzburg, 97080
France5 sites
Hopital Pellegrin; Rhumatologie
Bordeaux, 33076
Hopital de La Source
Orléans, 45067
Hopital Cochin; Rhumatologie B
Paris, 75679
Hopital Hautepierre; Rhumatologie
Strasbourg, 67098
Hopital Purpan; Rhumatologie
Toulouse, 31059
Russia5 sites
FSBI Scientific Research Institute of Clinical and Experimental Lymphology of SB of RAMS
Novosibirsk, 630117
Perm Regional Clinical Hospital
Perm, 614000
SBEI of HPE "Northwestern State Medical University n.a. I.I.Mechnikov" of MoH of RF
Saint Petersburg, 195067
Republican clinical hospital named after G.G. Kuvatov
Ufa, 450005
City Clinical Hospital # 2
Vladivostok, 690105
Serbia5 sites
Institute of Rheumatology
Belgrade, 11000
Military Medical Academy; Clinic of Rheumatology
Belgrade, 11000
Institute of Rheumatology and Cardiovascular Diseases; Rheumatology
Niška Banja, 18205
Clinical Center of Vojvodina
Novi Sad, 21000
Special hospital for rheumatic diseases Novi Sad
Novi Sad, 21000
Italy3 sites
Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia
Florence, Tuscany, 50139
Irccs Policlinico San Matteo; Reumatologia Adulti
Pavia, Lombardy, 27100
Arcispedale Santa Maria Nuova; Reumatologia
Reggio Emilia, Emilia-Romagna, 42100
About this study
Official 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
This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial compares the change in disease activity (as assessed by Disease Activity Score in 28 joints [DAS28] erythrocyte sedimentation rate [ESR]) from randomization to Week 24 post-randomization, in participants with stable low disease activity [LDA] (DAS28 ESR score less than or equal to [<=] 3.2) who receive tocilizumab, and have been randomized to either continue or taper prednisone in a double-blinded fashion.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Placebo matched to prednisone, Prednisone, Tocilizumab
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo matched to prednisoneDrug
Participants will receive placebo matched to prednisone orally for 24 weeks.
PrednisoneDrug
Participants will receive prednisone either at a constant dose of 5 mg/day, or 5 mg/day with 1 mg decrements every 4 weeks orally for 24 weeks.
TocilizumabBiological
Participants will receive tocilizumab at a dose of 162 mg once a week subcutaneously for 24 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab+prednisone (constant dose) | Experimental | Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. Receives: Drug: Placebo matched to prednisone; Drug: Prednisone; Biological: Tocilizumab |
| Tocilizumab+prednisone (tapering dose) | Experimental | Participants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. Receives: Drug: Placebo matched to prednisone; Drug: Prednisone; Biological: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Disease Activity Score in 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 Post-randomization
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: Baseline to Week 24
Secondary outcomes (22)
Treatment Success
Treatment success was defined as the percentage of participants with stable low disease activity (LDA) (DAS28-ESR score ≤ 3.2) at Week 24 post-randomization, who did not suffer a flare due to RA and who showed no confirmed adrenal insufficiency that required replacement therapy. DAS28 has the following standardized cut-offs for disease activity and remission: DAS28 > 5.1 = high disease activity; DAS28 between 3.2 and 5.1 = moderate disease activity; DAS28 ≤ 3.2 = low disease activity; DAS28 ≤ 2.6 = remission.
Measured: Week 24
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Clinical Disease Activity Index (CDAI) is an index for measuring disease activity in rheumatoid arthritis (RA). The index is calculated using the following formula: CDAI = number of swollen joints using the 28-joint count (SJC28) + number of tender joints using the 28-joint count (TJC28) + patient global assessment of disease (PGA) based on 10 centimeter (cm) visual analog scale (VAS) + physician global assessment of disease (PhGA) based on 10 cm VAS. VAS assessments involved a 100 mm horizontal scale from 0 (no disease activity) to 10 (maximum disease activity). Total CDAI scores range from 0 to 76, with higher scores indicating increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: Baseline and Week 24
Percentage of Participants With >=1 Flare
Percentage of participants with >=1 flare
Measured: 24 weeks
Time to First RA Flare
The mean time of onset for the first RA flare since randomization.
Measured: Randomization to 24 weeks
Percentage of Visits With RA Flares
Measured: Randomization to 24 weeks
Percentage of Participants With >=1 Administration of Flare Rescue Medication
The proportion of participants with at least one administration of RA flare rescue medication.
Measured: Randomization to 24 weeks
Time to First Administration of Flare Rescue Medication
Time of onset of first administration of RA flare rescue medication since randomization date
Measured: Randomization to 24 weeks
Number of Administrations of Flare Rescue Medication
Proportion of participants who received courses of RA flare rescue medication by number of courses received.
Measured: Randomization to 24 weeks
Cumulative Prednisone Exposure (Dose)
In Post-randomization prednisone arm, Cumulative dose = (number of capsules taken during week 1 to 4 * 1 mg) + (3/4 * number of capsules taken during week 5 to 8 * 1 mg) + (1/2 * number of capsules taken during week 9 to 12 * 1 mg) + (1/4 * number of capsules taken during week 13 to 16 * 1 mg). In continued arm, cumulative dose = (1/4 * number of capsule taken * 5 mg).
Cumulative prednisone dose is defined as cumulative blinded prednisone + cumulative flare rescue prednisone.
Measured: 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
The proportion of participants who maintained LDA and the proportion of participants who maintained the baseline disease activity level at Week 24.
LDA was defined as DAS28 ESR score <= 3.2. Remission was defined as DAS28 ESR score <= 2.6. Participants who maintained the baseline activity was defined as DAS28-ESR at Week 24 <= DAS28-ESR at baseline.
Measured: Randomization to Week 24
Percentage of Participants Who Permanently Discontinue Study Treatment Due to Insufficient Flare Control
Percentage of participants who permanently discontinue study treatment due to insufficient flare control
Measured: 24 weeks
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Swollen 66 Joint Counts
Count of swollen joints based upon 66 assessed joints.
Measured: Baseline to Week 24
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Tender 68 Joint Counts
Count of tender joints based on 68 assessed joints.
Measured: Baseline to Week 24
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Patient's Assessment of Pain
The ACR patient's assessment of pain is scored on a visual analog scale (VAS) from 0 (no pain) to 100 mm (unbearable pain). A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: 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
The ACR patient's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: 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
The ACR physician's global assessment of disease activity is scored on a visual analog scale (VAS) from 0 (symptom-free and no arthritis symptoms) to 100 mm (maximum arthritis disease activity). A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: 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)
A measure of self-perceived disability containing 20 questions in eight categories and including additional section about aid from other people and devices needed to correct the disabilities. Scores range from 0 to 3, with higher scores indicating worse disability.
Measured: 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)
Change from baseline in the acute phase reactant hsCRP
Measured: Baseline to Week 24
Changes From Baseline in American College of Rheumatology (ACR) Core Set Components at Week 24: Erythrocyte Sedimentation Rate (ESR)
Change from baseline in the acute phase reactant ESR
Measured: Baseline to Week 24
Changes From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Final Score
The RAID is a participant-completed questionnaire specific for RA consisting of a 0-10 rating for pain, functional disability, fatigue, sleep, physical well-being, emotional well-being and coping. Scores are weighted to produce a final numerical result. A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: Baseline and Week 24
Changes From Baseline in Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) Score
The WPAI:SHP is a 6-item questionnaire to measure performance impairment of work and regular daily activity and yields 4 types of scores: work time missed (absenteeism), impairment while working (presenteeism or reduced on-the-job effectiveness), overall work impairment (WI) (work productivity loss or absenteeism plus presenteeism) and activity impairment (daily activity impairment). Total score and each score range from 0 (not affected/no impairment) to 100 (completely affected/impaired). Higher scores indicate greater impairment and less productivity. A positive change in score indicates impairment, and a negative change indicates improvement.
Measured: Baseline and Week 24
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24
The SDAI is the numerical sum of 5 outcome parameters: tender and swollen joint count based on a 28-joint assessment, patient and physician global assessment of disease activity according to 100-mm visual analog scale (VAS) and level of C-reactive protein in milligrams per deciliter (mg/dL, normal <1 mg/dl). The total SDAI score range is 0-86, where higher scores indicate increased disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
Measured: Randomization to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2015 (estimated)
- Study start29 Mar 2016
- Primary completion9 Feb 2018
- Study completion9 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 314 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02573012
- Sponsor's protocol ID
- MA29585
- Other IDs
- 2014-004673-16, 2014
- Status last verified
- Oct 2019
- First submitted
- 1 Oct 2015
- Last updated
- 1 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Burmester GR, Buttgereit F, Bernasconi C, Alvaro-Gracia JM, Castro N, Dougados M, Gabay C, van Laar JM, Nebesky JM, Pethoe-Schramm A, Salvarani C, Donath MY, John MR; SEMIRA collaborators. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Lancet. 2020 Jul 25;396(10246):267-276. doi: 10.1016/S0140-6736(20)30636-X.
PubMed 32711802
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02573012
- Acronym / sponsor ID
- MA29585
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 314 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2016 (actual)
- Primary completion
- 9 Feb 2018 (actual)
- Study completion
- 9 Feb 2018 (actual)
- First posted
- 9 Oct 2015 (estimated)
- Results
- Posted 24 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase IIIb/IV, two-arm, randomized, double-blind, placebo-controlled, parallel-group, international, multicenter trial compares the change in disease activity (as assessed by Disease Activity Score in 28 joints [DAS28] erythrocyte sedimentation rate [ESR]) from randomization to Week 24 post-randomization, in participants with stable low disease activity [LDA] (DAS28 ESR score less than or equal to [<=] 3.2) who receive tocilizumab, and have been randomized to either continue or taper prednisone in a double-blinded fashion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab+prednisone (constant dose) | Experimental | Drug: Placebo matched to prednisone, Drug: Prednisone, Biological: TocilizumabParticipants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) or matching placebo orally for 24 weeks. |
| Tocilizumab+prednisone (tapering dose) | Experimental | Drug: Placebo matched to prednisone, Drug: Prednisone, Biological: TocilizumabParticipants will receive tocilizumab at a dose of 162 milligram (mg) once a week subcutaneously; and prednisone at a dose of 5 milligram per day (mg/day) with 1 mg decrements every 4 weeks or matching placebo orally for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (37 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo matched to prednisoneParticipants will receive placebo matched to prednisone orally for 24 weeks. | Drug | Tocilizumab+prednisone (constant dose), Tocilizumab+prednisone (tapering dose) |
| PrednisoneParticipants will receive prednisone either at a constant dose of 5 mg/day, or 5 mg/day with 1 mg decrements every 4 weeks orally for 24 weeks. | Drug | Tocilizumab+prednisone (constant dose), Tocilizumab+prednisone (tapering dose) |
| TocilizumabParticipants will receive tocilizumab at a dose of 162 mg once a week subcutaneously for 24 weeks. | Biological | Tocilizumab+prednisone (constant dose), Tocilizumab+prednisone (tapering dose) |
Primary outcome
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
The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint count, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100-millimeter (mm) visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A positive change in score indicates worsening, and a negative change indicates improvement.
22 secondary outcomes
Treatment Success
Time frame: Week 24
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24
Time frame: Baseline and Week 24
Percentage of Participants With >=1 Flare
Time frame: 24 weeks
Time to First RA Flare
Time frame: Randomization to 24 weeks
Percentage of Visits With RA Flares
Time frame: Randomization to 24 weeks
Percentage of Participants With >=1 Administration of Flare Rescue Medication
Time frame: Randomization to 24 weeks
Time to First Administration of Flare Rescue Medication
Time frame: Randomization to 24 weeks
Number of Administrations of Flare Rescue Medication
Time frame: Randomization to 24 weeks
Cumulative Prednisone Exposure (Dose)
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
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 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: 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: Erythrocyte Sedimentation Rate (ESR)
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
Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 24
Time frame: Randomization to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32711802Burmester GR, Buttgereit F, Bernasconi C, Alvaro-Gracia JM, Castro N, Dougados M, Gabay C, van Laar JM, Nebesky JM, Pethoe-Schramm A, Salvarani C, Donath MY, John MR; SEMIRA collaborators. Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial. Lancet. 2020 Jul 25;396(10246):267-276. doi: 10.1016/S0140-6736(20)30636-X.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
39 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prednisone and Tocilizumab in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 39 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in Germany, France, Russia, Serbia, Italy and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02573012, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.