An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)

NCT ID: NCT01791153

Last Updated: 2020-02-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

251 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-07-22

Study Completion Date

2018-06-04

Brief Summary

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This multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of tocilizumab in participants with GCA. The study will consist of 2 parts: a 52-week double-blind treatment period (Part 1) followed by a 104-week open label long-term follow-up period (Part 2). In Part 1 of the study eligible participants will be randomized to receive either tocilizumab every week (qw) or every 2 weeks (q2w) or placebo for 52 weeks, with tapering oral daily doses of prednisone. After Week 52, participants in remission will stop study treatment and enter long-term follow-up, whereas participants with disease activity or flares will receive open-label tocilizumab or other treatment at the discretion of the investigator for a maximum period of 104 weeks.

Detailed Description

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Conditions

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Giant Cell Arteritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Part 1: Tocilizumab qw + 26 weeks prednisone taper

Participants will receive tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.

Prednisone

Intervention Type DRUG

Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.

Prednisone Placebo

Intervention Type DRUG

Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.

Part 1: Tocilizumab q2w + 26 weeks prednisone taper

Participants will receive tocilizumab at a dose of 162 mg as SC injection q2w (and tocilizumab placebo q2w starting from Week 2) up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.

Prednisone

Intervention Type DRUG

Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.

Tocilizumab Placebo

Intervention Type DRUG

Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.

Prednisone Placebo

Intervention Type DRUG

Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.

Part 1: Placebo + 26 weeks prednisone taper

Participants will receive tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to the protocol-defined schedule. Participants will receive prednisone tapering oral daily doses during the first 26 weeks and prednisone placebo from Week 26 up to Week 52.

Group Type PLACEBO_COMPARATOR

Prednisone

Intervention Type DRUG

Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.

Tocilizumab Placebo

Intervention Type DRUG

Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.

Prednisone Placebo

Intervention Type DRUG

Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.

Part 1: Placebo + 52 weeks prednisone taper

Participants will receive tocilizumab placebo as SC injection qw up to 52 weeks along with prednisone and/or prednisone placebo according to a protocol-defined schedule. Participants will receive prednisone tapering oral daily doses for 52 weeks.

Group Type PLACEBO_COMPARATOR

Prednisone

Intervention Type DRUG

Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.

Tocilizumab Placebo

Intervention Type DRUG

Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.

Prednisone Placebo

Intervention Type DRUG

Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.

Part 2: Open-Label Tocilizumab qw

Participants without sustained remission at Week 52 will receive open-label tocilizumab at a dose of 162 mg as SC injection qw and/or corticosteroids and/or methotrexate at the discretion of the investigator for a maximum of 104 weeks.

Group Type EXPERIMENTAL

Tocilizumab

Intervention Type DRUG

Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.

Corticosteroids

Intervention Type DRUG

Participants without sustained remission at Week 52 will receive corticosteroids at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.

Methotrexate

Intervention Type DRUG

Participants without sustained remission at Week 52 will receive methotrexate at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.

Interventions

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Tocilizumab

Tocilizumab will be administered at a dose of 162 mg as SC injection qw or q2w for 52 weeks in Part 1 of the study and at a dose 162 mg as SC injection qw for 104 week at the discretion of the investigator in Part 2 of the study.

Intervention Type DRUG

Prednisone

Prednisone will be administered at tapering oral doses as tablets daily for 26 or 52 weeks according to the protocol-defined schedule in Part 1 of the study. Prednisone will also be administered as escape therapy to treat disease flares in an open-label manner during Part 1 at a dose and duration selected by the investigator.

Intervention Type DRUG

Tocilizumab Placebo

Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.

Intervention Type DRUG

Prednisone Placebo

Prednisone placebo will be administered as tablets orally daily according to the protocol-defined schedule (from Week 26 to Week 52) in Part 1 of the study.

Intervention Type DRUG

Corticosteroids

Participants without sustained remission at Week 52 will receive corticosteroids at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.

Intervention Type DRUG

Methotrexate

Participants without sustained remission at Week 52 will receive methotrexate at a dose and schedule at the discretion of the investigator for a maximum of 104 weeks.

Intervention Type DRUG

Other Intervention Names

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RoActemra, Actemra, RO4877533

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of GCA classified according to age \>/=50 years; history of ESR \>/=50 mm/hr or history of CRP \>/=2.45 mg/dL; and at least one of the following: unequivocal cranial symptoms of GCA or symptoms of polymyalgia rheumatica \[PMR\]; and at least one of the following: temporal artery biopsy revealing features of GCA or evidence of large-vessel vasculitis by angiography or cross-sectional imaging
* New onset (diagnosis within 6 weeks of baseline) or refractory (diagnosis greater than \[\>\] 6 weeks before baseline and previous treatment with \>/= 40 milligrams per day prednisone \[or equivalent\] for at least 2 consecutive weeks at any time) GCA
* Active disease (presence of clinical signs and symptoms \[cranial or PMR\] and ESR \>/=30 mm/hour or CRP \>/=1 mg/dL) within 6 weeks of baseline visit

Exclusion Criteria

* Major surgery within 8 weeks prior to screening or planned within 12 months after randomization
* Transplanted organs (except corneas with transplant performed \>3 months prior to screening)
* Major ischemic event, unrelated to GCA, within 12 weeks of screening
* Prior treatment with any of the following: investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening; cell-depleting therapies including investigational agent; intravenous (IV) gamma globulin or plasmapheresis within 6 months of baseline; alkylating agents or with total lymphoid irradiation; tocilizumab; hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil within 4 weeks of baseline; etanercept within 2 weeks of baseline; infliximab, certolizumab, golimumab, abatacept, or adalimumab within 8 weeks of baseline; anakinra within 1 week of baseline; tofacitinib; cyclophosphamide within 6 months of baseline; \>100 milligrams of daily IV methylprednisolone within 6 weeks of baseline
* Participants requiring systemic glucocorticoids for conditions other than GCA, which, in the opinion of the investigator, would interfere with adherence to the fixed glucocorticoid taper regimen and/or to assessment of efficacy in response to the test article
* History of severe allergic reactions to monoclonal antibodies or to prednisone
* Evidence of serious uncontrolled concomitant disease (for example, cardiovascular, respiratory, renal, endocrine, psychiatric, corneal ulcers/injuries, or gastrointestinal \[GI\] disease)
* Current liver disease, as determined by the investigator
* History of diverticulitis, inflammatory bowel disease, or other symptomatic GI tract condition that might predispose to bowel perforation
* Known active or history of recurrent bacterial, viral fungal, mycobacterial, or other infection
* Primary or secondary immunodeficiency
* Evidence of malignancies diagnosed within previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that have been excised and cured)
* Inadequate hematologic, renal or liver function
* Positive for hepatitis B or hepatitis C infection
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Univ of Calif., Los Angeles; Rheumatology

Los Angeles, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Rheumatology Assoc. of S. Florida - Clinical Research Center

Boca Raton, Florida, United States

Site Status

Sarasota Arthritis Res Center

Sarasota, Florida, United States

Site Status

Four Rivers Clinical Research Inc.

Paducah, Kentucky, United States

Site Status

Rheumatology Associates

Portland, Maine, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Shores Rheumatology

Saint Clair Shores, Michigan, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

Hospital For Special Surgery; Dept of Medicine - Rheumatology

New York, New York, United States

Site Status

Asheville Arthritis & Osteoporosis Center, PA

Asheville, North Carolina, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Utah; Division of Rheumatology

Salt Lake City, Utah, United States

Site Status

Marshfield Clinic Wausau Ctr

Wausau, Wisconsin, United States

Site Status

Hospital Erasme

Brussels, , Belgium

Site Status

UZ Leuven Gasthuisberg

Leuven, , Belgium

Site Status

Clin. de Rhumatologie

Trois-Rivières, Quebec, Canada

Site Status

Nordsjællands Hospital - Hillerød;Department of Rheumatology 0731

Hillerød, , Denmark

Site Status

Hopital Avicenne; Medecine Interne H5

Bobigny, , France

Site Status

Hopital La Cavale Blanche; Rhumatologie

Brest, , France

Site Status

Hopital Claude Huriez; Internal Medicine

Lille, , France

Site Status

Hôpital de la Conception

Marseille, , France

Site Status

Hopital Emile Muller; Medecine Interne

Mulhouse, , France

Site Status

Hopital Cochin; Medecine Interne

Paris, , France

Site Status

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

Bad Abbach, , Germany

Site Status

Rheuma-Klinikum Bad Bramstedt Klinik fuer Rheumatologie und Immunologie

Bad Bramstedt, , Germany

Site Status

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

Berlin, , Germany

Site Status

Schlosspark Klinik; Abt. Rheumatologie

Berlin, , Germany

Site Status

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III

Dresden, , Germany

Site Status

Universitätsklinikum Erlangen; Medizinische Klinik 3; Rheumatologie und Immunologie

Erlangen, , Germany

Site Status

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie

Hanover, , Germany

Site Status

Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie

Herne, , Germany

Site Status

Universitätsklinikum Jena; Klinik für Innere Medizin III

Jena, , Germany

Site Status

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie

Mainz, , Germany

Site Status

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

München, , Germany

Site Status

Kreiskliniken Esslingen gGmbH Klinik Plochingen Medizinische Klinik

Plochingen, , Germany

Site Status

Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II

Tübingen, , Germany

Site Status

Arcispedale Santa Maria Nuova; Reumatologia

Reggio Emilia, Emilia-Romagna, Italy

Site Status

Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia

Udine, Friuli Venezia Giulia, Italy

Site Status

Università Degli Studi Di Genova - Dimi; Reumatologia

Genoa, Liguria, Italy

Site Status

Irccs San Raffele; Div Med Gen Immunologia Clinica

Milan, Lombardy, Italy

Site Status

A.O. Universitaria Pisana; Psichiatria

Pisa, Tuscany, Italy

Site Status

Azienda Ospedaliera di Padova; Cattedra e Divisione di Reumatologia

Padua, Veneto, Italy

Site Status

Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

Verona, Veneto, Italy

Site Status

VU Medisch Centrum; Reumatologie 4-A-A2

Amsterdam, , Netherlands

Site Status

Ziekenhuis Rijnstate

Arnhem, , Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Ziekenhuisgroep Twente, Hengelo

Hengelo, , Netherlands

Site Status

Akademisch Ziekenhuis St. Radboud; Rheumatology

Nijmegen, , Netherlands

Site Status

Ålesund sjukehus

Ålesund, , Norway

Site Status

Sørlandet Sykehus Kristiansand

Kristiansand, , Norway

Site Status

Rikshospitalet; Revmatologisk Avd Seksjon Barnerevmatologi

Oslo, , Norway

Site Status

Szpital Uniwersytecki; nr 2 im. Dr J. Biziela

Bydgoszcz, , Poland

Site Status

Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1

Szczecin, , Poland

Site Status

Hospital Geral de Santo Antonio; Servico de Imunologia Clinica

Porto, , Portugal

Site Status

Hospital Univ A Coruna; Rheumatology

A Coruña, LA Coruña, Spain

Site Status

Hospital Universitario de Canarias;servicio de Reumatologia

San Cristóbal de La Laguna, Tenerife, Spain

Site Status

Hospital de Basurto; Servicio de Reumatologia

Bilbao, Vizcaya, Spain

Site Status

Hospital Universitari de Bellvitge; Servicio de Reumatologia

Barcelona, , Spain

Site Status

University of Barcelona; Dept. of Internal Medicine,

Barcelona, , Spain

Site Status

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Site Status

Skånes Universitetssjukhus

Lund, , Sweden

Site Status

Skånes Universitetssjukhus Malmö; Reumatologkliniken

Malmo, , Sweden

Site Status

Karolinska Sjukhuset; Reumatologkliniken D2-1

Stockholm, , Sweden

Site Status

Akademiska Sjukhuset; Lungmedicinska Kliniken

Uppsala, , Sweden

Site Status

Aberdeen Royal Infirmary; Medical Oncology Dept

Aberdeen, , United Kingdom

Site Status

Barnsley General Hospital; Rheumatology

Barnsley, , United Kingdom

Site Status

Old Queen Elizabeth Hospital; Pharmacy Building;Clinical Research offices

Birmingham, , United Kingdom

Site Status

Colchester General Hospital; Aseptic Dept, Pharmacy Support Unit

Colchester, Essex, , United Kingdom

Site Status

University of Edinburgh; The Queens Medical Research Institute

Edinburgh, , United Kingdom

Site Status

CHAPEL ALLERTON HOSPITAL; Unit of Musculoskeletal Disease

Leeds, , United Kingdom

Site Status

Moorfields Eye Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

Freeman Hospital; Dept of Rheumatology

Newcastle upon Tyne, , United Kingdom

Site Status

Queen's Hospital

Romford, , United Kingdom

Site Status

Haywood Hospital; Staffordshire Rheumatology Centre

Stoke-on-Trent, , United Kingdom

Site Status

Royal Cornwall Hospital; Rhuematololgy Dept

Truro, , United Kingdom

Site Status

Southend Hospital; Rheumatology Department

Westcliffe-on-sea, , United Kingdom

Site Status

Countries

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United States Belgium Canada Denmark France Germany Italy Netherlands Norway Poland Portugal Spain Sweden United Kingdom

References

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Stone JH, Han J, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera R, Unizony SH, Bao M; GiACTA investigators. Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial. Lancet Rheumatol. 2021 May;3(5):e328-e336. doi: 10.1016/S2665-9913(21)00038-2. Epub 2021 Mar 19.

Reference Type DERIVED
PMID: 38279390 (View on PubMed)

Stone JH, Spotswood H, Unizony SH, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Spiera R, Bao M. New-onset versus relapsing giant cell arteritis treated with tocilizumab: 3-year results from a randomized controlled trial and extension. Rheumatology (Oxford). 2022 Jul 6;61(7):2915-2922. doi: 10.1093/rheumatology/keab780.

Reference Type DERIVED
PMID: 34718434 (View on PubMed)

Unizony SH, Bao M, Han J, Luder Y, Pavlov A, Stone JH. Treatment failure in giant cell arteritis. Ann Rheum Dis. 2021 Nov;80(11):1467-1474. doi: 10.1136/annrheumdis-2021-220347. Epub 2021 May 28.

Reference Type DERIVED
PMID: 34049857 (View on PubMed)

Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schulze-Koops H, Schett G, Spiera R, Unizony SH, Collinson N. Glucocorticoid Dosages and Acute-Phase Reactant Levels at Giant Cell Arteritis Flare in a Randomized Trial of Tocilizumab. Arthritis Rheumatol. 2019 Aug;71(8):1329-1338. doi: 10.1002/art.40876. Epub 2019 Jul 3.

Reference Type DERIVED
PMID: 30835950 (View on PubMed)

Strand V, Dimonaco S, Tuckwell K, Klearman M, Collinson N, Stone JH. Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial. Arthritis Res Ther. 2019 Feb 20;21(1):64. doi: 10.1186/s13075-019-1837-7.

Reference Type DERIVED
PMID: 30786937 (View on PubMed)

Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, Brouwer E, Cid MC, Dasgupta B, Rech J, Salvarani C, Schett G, Schulze-Koops H, Spiera R, Unizony SH, Collinson N. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017 Jul 27;377(4):317-328. doi: 10.1056/NEJMoa1613849.

Reference Type DERIVED
PMID: 28745999 (View on PubMed)

Other Identifiers

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2011-006022-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA28119

Identifier Type: -

Identifier Source: org_study_id

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