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

NCT01791153 | Completed Phase 3 Results DMC

• 2 other identifiers: WA281192011-006022-25
• Study Type: interventional
• Target: 251
• Locations: 14 countries
• Sites: 78

Brief Summary

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.

Conditions

Giant Cell Arteritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)

  Remission was defined as the absence of flare and normalization of the C-reactive protein (CRP) (less than \[\<\] 1 milligram per deciliter \[mg/dL\]). Sustained remission was defined as the absence of flare following induction of remission within 12 weeks of randomization and maintained up to Week 52. Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) attributable to GCA. A single CRP elevation (\>/=1 mg/dL) was not considered as a sign of flare, unless the CRP remained elevated (\>/=1 mg/dL) at the next study visit.

  Week 52

Secondary Outcomes (14)

• Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)

  Week 52

• Time to First GCA Disease Flare

  Up to 52 weeks

• Total Cumulative Prednisone Dose

  Up to 52 weeks

• Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52

  Baseline, Week 52

• Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52

  Baseline, Week 52

Study Arms (5)

Part 1: Tocilizumab qw + 26 weeks prednisone taper

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Prednisone; Drug: Prednisone Placebo

Part 1: Tocilizumab q2w + 26 weeks prednisone taper

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Prednisone; Drug: Tocilizumab Placebo; Drug: Prednisone Placebo

Part 1: Placebo + 26 weeks prednisone taper

PLACEBO COMPARATOR

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.

Drug: Prednisone; Drug: Tocilizumab Placebo; Drug: Prednisone Placebo

Part 1: Placebo + 52 weeks prednisone taper

PLACEBO COMPARATOR

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.

Drug: Prednisone; Drug: Tocilizumab Placebo; Drug: Prednisone Placebo

Part 2: Open-Label Tocilizumab qw

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Corticosteroids; Drug: Methotrexate

Interventions

Tocilizumab 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.

Also known as: RoActemra, Actemra, RO4877533

Part 1: Tocilizumab q2w + 26 weeks prednisone taper; Part 1: Tocilizumab qw + 26 weeks prednisone taper; Part 2: Open-Label Tocilizumab qw

Prednisone 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.

Part 1: Placebo + 26 weeks prednisone taper; Part 1: Placebo + 52 weeks prednisone taper; Part 1: Tocilizumab q2w + 26 weeks prednisone taper; Part 1: Tocilizumab qw + 26 weeks prednisone taper

Tocilizumab Placebo DRUG

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

Part 1: Placebo + 26 weeks prednisone taper; Part 1: Placebo + 52 weeks prednisone taper; Part 1: Tocilizumab q2w + 26 weeks prednisone taper

Prednisone Placebo 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; Part 1: Placebo + 52 weeks prednisone taper; Part 1: Tocilizumab q2w + 26 weeks prednisone taper; Part 1: Tocilizumab qw + 26 weeks prednisone taper

Corticosteroids 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.

Part 2: Open-Label Tocilizumab qw

Methotrexate 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.

Part 2: Open-Label Tocilizumab qw

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (78)

Univ of Calif., Los Angeles; Rheumatology

Los Angeles, California, 90025, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Rheumatology Assoc. of S. Florida - Clinical Research Center

Boca Raton, Florida, 33486, United States

Location

Sarasota Arthritis Res Center

Sarasota, Florida, 34239, United States

Location

Four Rivers Clinical Research Inc.

Paducah, Kentucky, 42003, United States

Location

Rheumatology Associates

Portland, Maine, 04102, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Shores Rheumatology

Saint Clair Shores, Michigan, 48081, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

Hospital For Special Surgery; Dept of Medicine - Rheumatology

New York, New York, 10021, United States

Location

Asheville Arthritis & Osteoporosis Center, PA

Asheville, North Carolina, 28803, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah; Division of Rheumatology

Salt Lake City, Utah, 84132, United States

Location

Marshfield Clinic Wausau Ctr

Wausau, Wisconsin, 54401, United States

Location

Hospital Erasme

Brussels, 1070, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Clin. de Rhumatologie

Trois-Rivières, Quebec, G8Z 1Y2, Canada

Location

Nordsjællands Hospital - Hillerød;Department of Rheumatology 0731

Hillerød, 3400, Denmark

Location

Hopital Avicenne; Medecine Interne H5

Bobigny, 93009, France

Location

Hopital La Cavale Blanche; Rhumatologie

Brest, 29609, France

Location

Hopital Claude Huriez; Internal Medicine

Lille, 59037, France

Location

Hôpital de la Conception

Marseille, 13000, France

Location

Hopital Emile Muller; Medecine Interne

Mulhouse, 68070, France

Location

Hopital Cochin; Medecine Interne

Paris, 75679, France

Location

Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie

Bad Abbach, 93077, Germany

Location

Rheuma-Klinikum Bad Bramstedt Klinik fuer Rheumatologie und Immunologie

Bad Bramstedt, 24576, Germany

Location

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

Berlin, 10117, Germany

Location

Schlosspark Klinik; Abt. Rheumatologie

Berlin, 14059, Germany

Location

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen; Medizinische Klinik 3; Rheumatologie und Immunologie

Erlangen, 91054, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie

Hanover, 30625, Germany

Location

Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie

Herne, 44652, Germany

Location

Universitätsklinikum Jena; Klinik für Innere Medizin III

Jena, 07747, Germany

Location

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

Mainz, 55131, Germany

Location

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

München, 80336, Germany

Location

Kreiskliniken Esslingen gGmbH Klinik Plochingen Medizinische Klinik

Plochingen, 73207, Germany

Location

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

Tübingen, 72076, Germany

Location

Arcispedale Santa Maria Nuova; Reumatologia

Reggio Emilia, Emilia-Romagna, 42100, Italy

Location

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

Udine, Friuli Venezia Giulia, 33100, Italy

Location

Università Degli Studi Di Genova - Dimi; Reumatologia

Genoa, Liguria, 16132, Italy

Location

Irccs San Raffele; Div Med Gen Immunologia Clinica

Milan, Lombardy, 20132, Italy

Location

A.O. Universitaria Pisana; Psichiatria

Pisa, Tuscany, 56126, Italy

Location

Azienda Ospedaliera di Padova; Cattedra e Divisione di Reumatologia

Padua, Veneto, 35128, Italy

Location

Azienda Ospedaliera di Verona-Ospedale Civile Maggiore

Verona, Veneto, 37126, Italy

Location

VU Medisch Centrum; Reumatologie 4-A-A2

Amsterdam, 1081 HV, Netherlands

Location

Ziekenhuis Rijnstate

Arnhem, 6815 AD, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Ziekenhuisgroep Twente, Hengelo

Hengelo, 7555 DL, Netherlands

Location

Akademisch Ziekenhuis St. Radboud; Rheumatology

Nijmegen, 6525 GA, Netherlands

Location

Ålesund sjukehus

Ålesund, N-6026, Norway

Location

Sørlandet Sykehus Kristiansand

Kristiansand, 4604, Norway

Location

Rikshospitalet; Revmatologisk Avd Seksjon Barnerevmatologi

Oslo, 0027, Norway

Location

Szpital Uniwersytecki; nr 2 im. Dr J. Biziela

Bydgoszcz, 85-168, Poland

Location

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

Szczecin, 71-252, Poland

Location

Hospital Geral de Santo Antonio; Servico de Imunologia Clinica

Porto, 4099-001, Portugal

Location

Hospital Univ A Coruna; Rheumatology

A Coruña, LA Coruña, 15006, Spain

Location

Hospital Universitario de Canarias;servicio de Reumatologia

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Hospital de Basurto; Servicio de Reumatologia

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Universitari de Bellvitge; Servicio de Reumatologia

Barcelona, 08907, Spain

Location

University of Barcelona; Dept. of Internal Medicine,

Barcelona, 8036, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, 413 45, Sweden

Location

Skånes Universitetssjukhus

Lund, 221 85, Sweden

Location

Skånes Universitetssjukhus Malmö; Reumatologkliniken

Malmo, 205 02, Sweden

Location

Karolinska Sjukhuset; Reumatologkliniken D2-1

Stockholm, 171 76, Sweden

Location

Akademiska Sjukhuset; Lungmedicinska Kliniken

Uppsala, 751 85, Sweden

Location

Aberdeen Royal Infirmary; Medical Oncology Dept

Aberdeen, AB25 2ZN, United Kingdom

Location

Barnsley General Hospital; Rheumatology

Barnsley, S75 2EP, United Kingdom

Location

Old Queen Elizabeth Hospital; Pharmacy Building;Clinical Research offices

Birmingham, B15 2TH, United Kingdom

Location

Colchester General Hospital; Aseptic Dept, Pharmacy Support Unit

Colchester, Essex, CO4 5JL, United Kingdom

Location

University of Edinburgh; The Queens Medical Research Institute

Edinburgh, EH16 4TJ, United Kingdom

Location

CHAPEL ALLERTON HOSPITAL; Unit of Musculoskeletal Disease

Leeds, LS7 4SA, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

Freeman Hospital; Dept of Rheumatology

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Queen's Hospital

Romford, RM7 0AG, United Kingdom

Location

Haywood Hospital; Staffordshire Rheumatology Centre

Stoke-on-Trent, ST6 7AG, United Kingdom

Location

Royal Cornwall Hospital; Rhuematololgy Dept

Truro, TR1 3LJ, United Kingdom

Location

Southend Hospital; Rheumatology Department

Westcliffe-on-sea, SS0 0RY, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 38279390 DERIVED

• 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.

  PMID: 34718434 DERIVED

• 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.

  PMID: 34049857 DERIVED

• 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.

  PMID: 30835950 DERIVED

• 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.

  PMID: 30786937 DERIVED

• 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.

  PMID: 28745999 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

tocilizumab; Prednisone; Adrenal Cortex Hormones; Methotrexate

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 13, 2013
• Study Start: July 22, 2013
• Primary Completion: April 11, 2016
• Study Completion: June 4, 2018
• Last Updated: February 6, 2020
• Results First Posted: May 18, 2017

Record last verified: 2020-02

Locations

SE (5); GB (12); DK (1); NO (3); CA (1); DE (14); PT (1); US (14); PL (2); IT (7); BE (2); NL (5); ES (5); FR (6)