Study to Compare the Efficacy of Tocilizumab With or Without Glucocorticoid Discontinuation in Rheumatoid Arthritis Participants

NCT02573012 | Completed Phase 4 Results

• 2 other identifiers: MA295852014-004673-16
• Study Type: interventional
• Target: 314
• Locations: 6 countries
• Sites: 39

Brief 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 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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 24

Secondary Outcomes (22)

• Treatment Success

  Week 24

• Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24

  Baseline and Week 24

• Percentage of Participants With >=1 Flare

  24 weeks

• Time to First RA Flare

  Randomization to 24 weeks

• Percentage of Visits With RA Flares

  Randomization to 24 weeks

Study Arms (2)

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.

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.

Drug: Placebo matched to prednisone; Drug: Prednisone; Biological: Tocilizumab

Interventions

Placebo matched to prednisone DRUG

Participants will receive placebo matched to prednisone orally for 24 weeks.

Tocilizumab+prednisone (constant dose); Tocilizumab+prednisone (tapering dose)

Prednisone DRUG

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.

Tocilizumab+prednisone (constant dose); Tocilizumab+prednisone (tapering dose)

Tocilizumab BIOLOGICAL

Participants will receive tocilizumab at a dose of 162 mg once a week subcutaneously for 24 weeks.

Tocilizumab+prednisone (constant dose); Tocilizumab+prednisone (tapering dose)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (39)

Hopital Pellegrin; Rhumatologie

Bordeaux, 33076, France

Location

Hopital de La Source

Orléans, 45067, France

Location

Hopital Cochin; Rhumatologie B

Paris, 75679, France

Location

Hopital Hautepierre; Rhumatologie

Strasbourg, 67098, France

Location

Hopital Purpan; Rhumatologie

Toulouse, 31059, France

Location

Praxis Dr. med. Reiner Kurthen

Aachen, 52064, Germany

Location

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

Bad Abbach, 93077, Germany

Location

Rheumatologische Gemeinschaftspraxis Grafschaft, Dr. med. Dorothea Pick, Dr. med. Christopher Amberg

Bad Neuenahr-Ahrweiler, 53474, Germany

Location

Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie

Berlin, 10117, Germany

Location

SchlossPark-Klinik Berlin; Int. Med. II, Rheum. Osteo

Berlin, 14059, Germany

Location

Klinik der Uni zu Köln; Klinik für Innere Medizin

Cologne, 50924, Germany

Location

Rheumatologisches MVZ Dresden GmbH, Dres. Holger Schwenke, Reiner Schwenke, Annekatrin Georgi

Dresden, 01109, Germany

Location

MVZ Ambulantes Rheumazentrum

Erfurt, 99096, Germany

Location

Dres. Florian Schuch, Ruediger de la Camp, Martin Hammerschmidt u.w.

Erlangen, 91056, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Zentrum f.Innere Medizin Med.Klinik III

Hamburg, 20246, Germany

Location

Praxis Dr.med. Maria Höhle

Hamburg, 22147, Germany

Location

Rheumapraxis PD Dr.med. Bernhard Heilig

Heidelberg, 69120, Germany

Location

Rheumatologische Facharztpraxis Maren Sieburg

Magdeburg, 39104, Germany

Location

SMO.MD GmbH, Zentrum für klinische Studien

Magdeburg, 39120, Germany

Location

Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV

München, 80336, Germany

Location

Praxiszentrum St. Bonifatius

München, 81541, Germany

Location

Rheumapraxis an der Hase

Osnabrück, 49074, Germany

Location

Rheumazentrum Ratingen - Studienambulanz

Ratingen, 40878, Germany

Location

Rheumatologische Schwerpunktpraxis am Feuersee

Stuttgart, 70178, Germany

Location

Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Rheumatologie/Immunologie

Würzburg, 97080, Germany

Location

Arcispedale Santa Maria Nuova; Reumatologia

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

Irccs Policlinico San Matteo; Reumatologia Adulti

Pavia, Lombardy, 27100, Italy

Location

Ospedale Careggi Villa Monnatessa ; Sezione Di Reumatologia

Florence, Tuscany, 50139, Italy

Location

FSBI Scientific Research Institute of Clinical and Experimental Lymphology of SB of RAMS

Novosibirsk, 630117, Russia

Location

Perm Regional Clinical Hospital

Perm, 614000, Russia

Location

SBEI of HPE "Northwestern State Medical University n.a. I.I.Mechnikov" of MoH of RF

Saint Petersburg, 195067, Russia

Location

Republican clinical hospital named after G.G. Kuvatov

Ufa, 450005, Russia

Location

City Clinical Hospital # 2

Vladivostok, 690105, Russia

Location

Institute of Rheumatology

Belgrade, 11000, Serbia

Location

Military Medical Academy; Clinic of Rheumatology

Belgrade, 11000, Serbia

Location

Institute of Rheumatology and Cardiovascular Diseases; Rheumatology

Niška Banja, 18205, Serbia

Location

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

Location

Special hospital for rheumatic diseases Novi Sad

Novi Sad, 21000, Serbia

Location

Hopital Farhat Hached; Service Rhumatologie

Sousse, 4000, Tunisia

Location

Related Publications (1)

• 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.

  PMID: 32711802 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Prednisone; tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann- LaRoche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2015
• First Posted: October 9, 2015
• Study Start: March 29, 2016
• Primary Completion: February 9, 2018
• Study Completion: February 9, 2018
• Last Updated: November 1, 2019
• Results First Posted: July 24, 2019

Record last verified: 2019-10

Locations

FR (5); DE (20); RU (5); SE (5); TU (1); IT (3)