Giant Cell ArteritisPhase 3NCT01791153
An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)
A Phase 3 study testing Tocilizumab, Prednisone and Corticosteroids in people with Giant Cell Arteritis, run by Hoffmann-La Roche at 78 sites in 14 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Giant Cell Arteritis
- What is being tested?
- Tocilizumab, Prednisone and Corticosteroids
- 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
- 251 participants
- Where
- 78 sitesin 14 countries
- Study dates
- 22 Jul 2013to 4 Jun 2018
- Phase
- Phase 3
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
78 sites in 14 countries.
78 sites in 14 countries
United States14 sites
Asheville Arthritis & Osteoporosis Center, PA
Asheville, North Carolina, 28803
Rheumatology Assoc. of S. Florida - Clinical Research Center
Boca Raton, Florida, 33486
Massachusetts General Hospital
Boston, Massachusetts, 02114
Univ of Calif., Los Angeles; Rheumatology
Los Angeles, California, 90025
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Hospital For Special Surgery; Dept of Medicine - Rheumatology
New York, New York, 10021
Four Rivers Clinical Research Inc.
Paducah, Kentucky, 42003
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Rheumatology Associates
Portland, Maine, 04102
Mayo Clinic Rochester
Rochester, Minnesota, 55902
Shores Rheumatology
Saint Clair Shores, Michigan, 48081
University of Utah; Division of Rheumatology
Salt Lake City, Utah, 84132
Sarasota Arthritis Res Center
Sarasota, Florida, 34239
Marshfield Clinic Wausau Ctr
Wausau, Wisconsin, 54401
Germany14 sites
Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
Bad Abbach, 93077
Rheuma-Klinikum Bad Bramstedt Klinik fuer Rheumatologie und Immunologie
Bad Bramstedt, 24576
Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie
Berlin, 10117
Schlosspark Klinik; Abt. Rheumatologie
Berlin, 14059
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
Dresden, 01307
Universitätsklinikum Erlangen; Medizinische Klinik 3; Rheumatologie und Immunologie
Erlangen, 91054
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie
Hanover, 30625
Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie
Herne, 44652
Universitätsklinikum Jena; Klinik für Innere Medizin III
Jena, 07747
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
Mainz, 55131
Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
München, 80336
Kreiskliniken Esslingen gGmbH Klinik Plochingen Medizinische Klinik
Plochingen, 73207
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Tübingen, 72076
United Kingdom12 sites
Aberdeen Royal Infirmary; Medical Oncology Dept
Aberdeen, AB25 2ZN
Barnsley General Hospital; Rheumatology
Barnsley, S75 2EP
Old Queen Elizabeth Hospital; Pharmacy Building;Clinical Research offices
Birmingham, B15 2TH
Colchester General Hospital; Aseptic Dept, Pharmacy Support Unit
Colchester, Essex, CO4 5JL
University of Edinburgh; The Queens Medical Research Institute
Edinburgh, EH16 4TJ
CHAPEL ALLERTON HOSPITAL; Unit of Musculoskeletal Disease
Leeds, LS7 4SA
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
Freeman Hospital; Dept of Rheumatology
Newcastle upon Tyne, NE7 7DN
Queen's Hospital
Romford, RM7 0AG
Haywood Hospital; Staffordshire Rheumatology Centre
Stoke-on-Trent, ST6 7AG
Royal Cornwall Hospital; Rhuematololgy Dept
Truro, TR1 3LJ
Southend Hospital; Rheumatology Department
Westcliffe-on-sea, SS0 0RY
Italy7 sites
Università Degli Studi Di Genova - Dimi; Reumatologia
Genoa, Liguria, 16132
Irccs San Raffele; Div Med Gen Immunologia Clinica
Milan, Lombardy, 20132
Azienda Ospedaliera di Padova; Cattedra e Divisione di Reumatologia
Padova, Veneto, 35128
A.O. Universitaria Pisana; Psichiatria
Pisa, Tuscany, 56126
Arcispedale Santa Maria Nuova; Reumatologia
Reggio Emilia, Emilia-Romagna, 42100
Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia
Udine, Friuli Venezia Giulia, 33100
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
Verona, Veneto, 37126
France6 sites
Hopital Avicenne; Medecine Interne H5
Bobigny, 93009
Hopital La Cavale Blanche; Rhumatologie
Brest, 29609
Hopital Claude Huriez; Internal Medicine
Lille, 59037
Hôpital de la Conception
Marseille, 13000
Hopital Emile Muller; Medecine Interne
Mulhouse, 68070
Hopital Cochin; Medecine Interne
Paris, 75679
Netherlands5 sites
VU Medisch Centrum; Reumatologie 4-A-A2
Amsterdam, 1081 HV
Ziekenhuis Rijnstate
Arnhem, 6815 AD
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
Ziekenhuisgroep Twente, Hengelo
Hengelo, 7555 DL
Akademisch Ziekenhuis St. Radboud; Rheumatology
Nijmegen, 6525 GA
Spain5 sites
Hospital Univ A Coruna; Rheumatology
A Coruña, LA Coruña, 15006
Hospital Universitari de Bellvitge; Servicio de Reumatologia
Barcelona, 08907
University of Barcelona; Dept. of Internal Medicine,
Barcelona, 8036
Hospital de Basurto; Servicio de Reumatologia
Bilbao, Vizcaya, 48013
Hospital Universitario de Canarias;servicio de Reumatologia
San Cristóbal de La Laguna, Tenerife, 38320
Sweden5 sites
Sahlgrenska Universitetssjukhuset
Gothenburg, 413 45
Skånes Universitetssjukhus
Lund, 221 85
Skånes Universitetssjukhus Malmö; Reumatologkliniken
Malmö, 205 02
Karolinska Sjukhuset; Reumatologkliniken D2-1
Stockholm, 171 76
Akademiska Sjukhuset; Lungmedicinska Kliniken
Uppsala, 751 85
Norway3 sites
Ålesund sjukehus
Ålesund, N-6026
Sørlandet Sykehus Kristiansand
Kristiansand, 4604
Rikshospitalet; Revmatologisk Avd Seksjon Barnerevmatologi
Oslo, 0027
Belgium2 sites
Hospital Erasme
Brussels, 1070
UZ Leuven Gasthuisberg
Leuven, 3000
Poland2 sites
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
Bydgoszcz, 85-168
Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1
Szczecin, 71-252
Denmark1 site
Nordsjællands Hospital - Hillerød;Department of Rheumatology 0731
Hillerød, 3400
Portugal1 site
Hospital Geral de Santo Antonio; Servico de Imunologia Clinica
Porto, 4099-001
About this study
Official title: A Phase III, Multicenter, Randomized, Double-Blind Placebo-Controlled Study to Assess the Efficacy and Safety of Tocilizumab in Subjects With Giant Cell Arteritis
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
- Being tested
- Tocilizumab, Prednisone, Tocilizumab Placebo, Prednisone Placebo, Corticosteroids
- Medical subject headings
- Giant Cell Arteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called RoActemra, Actemra, RO4877533
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.
PrednisoneDrug
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 PlaceboDrug
Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.
Prednisone PlaceboDrug
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.
CorticosteroidsDrug
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.
MethotrexateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Tocilizumab; Drug: Corticosteroids; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Remission was defined as the absence of flare and normalization of the CRP (<1 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 ESR >/=30 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.
Measured: Week 52
Time to First GCA Disease Flare
Flare was determined by the investigator and was defined as the recurrence of signs or symptoms of GCA and/or ESR >/=30 mm/hr attributable to GCA. Participants who withdrew from the study prior to Week 52 were censored from the time of withdrawal.
Measured: Up to 52 weeks
Total Cumulative Prednisone Dose
The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented.
Measured: Up to 52 weeks
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52
The SF-36 is a standardized questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical Component Score (PCS) and Mental Component Score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). A positive change from baseline indicates improvement. No imputation was used for missing data. Data was set to missing for participants who received escape therapy.
Measured: Baseline, Week 52
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52
Participants assessed their current disease activity on a 0-100 millimeter (mm) VAS, where 0 mm = no disease activity and 100 mm = maximum disease activity. A negative change from baseline indicates improvement.
Measured: Baseline, Week 52
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab
AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval. AUCtau is measured in microgram*day per milliliter (mcg*day/mL).
Measured: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab
Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL).
Measured: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab
Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL.
Measured: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.
Measured: Predose (Hour 0) at Baseline and Week 52
Serum Interleukin-6 (IL-6) Level
Measured: Baseline and Week 52
Serum Soluble IL-6 Receptor (sIL-6R) Level
Measured: Baseline and Week 52
Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Measured: Baseline and Week 52
C-Reactive Protein (CRP) Level
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Measured: Baseline and Week 52
Percentage of Participants With Anti-Tocilizumab Antibodies
All samples were tested by screening assay, and those samples that were positive were further analyzed by a confirmation assay to confirm specificity. Percentage of participants who has a positive confirmation assay result any time after the initial drug administration with a negative confirmation assay result at baseline was reported.
Measured: Baseline up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study start22 Jul 2013
- Primary completion11 Apr 2016
- Study completion4 Jun 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 (6)Papers the sponsor has linked to this study.
- Other trials for Giant Cell ArteritisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 251 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
- NCT01791153
- Sponsor's protocol ID
- WA28119
- Other IDs
- 2011-006022-25
- Status last verified
- Feb 2020
- First submitted
- 12 Feb 2013
- Last updated
- 6 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 38279390Stone 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.
PubMed 34718434Unizony 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.
PubMed 34049857Stone 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.
PubMed 30835950Strand 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.
PubMed 30786937Stone 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.
PubMed 28745999
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Randomized, Double-Blind Placebo-Controlled Study to Assess the Efficacy and Safety of Tocilizumab in Subjects With Giant Cell Arteritis
- ClinicalTrials.gov ID
- NCT01791153
- Acronym / sponsor ID
- WA28119
- Conditions
- Giant Cell Arteritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 251 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 22 Jul 2013 (actual)
- Primary completion
- 11 Apr 2016 (actual)
- Study completion
- 4 Jun 2018 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Posted 18 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: Tocilizumab qw + 26 weeks prednisone taper | Experimental | Drug: Tocilizumab, Drug: Prednisone, Drug: Prednisone PlaceboParticipants 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. |
| Part 1: Tocilizumab q2w + 26 weeks prednisone taper | Experimental | Drug: Tocilizumab, Drug: Prednisone, Drug: Tocilizumab Placebo, Drug: Prednisone PlaceboParticipants 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. |
| Part 1: Placebo + 26 weeks prednisone taper | Placebo comparator | Drug: Prednisone, Drug: Tocilizumab Placebo, Drug: Prednisone PlaceboParticipants 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. |
| Part 1: Placebo + 52 weeks prednisone taper | Placebo comparator | Drug: Prednisone, Drug: Tocilizumab Placebo, Drug: Prednisone PlaceboParticipants 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. |
| Part 2: Open-Label Tocilizumab qw | Experimental | Drug: Tocilizumab, Drug: Corticosteroids, Drug: MethotrexateParticipants 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| TocilizumabAlso: RoActemra, Actemra, RO4877533Tocilizumab 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. | Drug | Part 1: Tocilizumab q2w + 26 weeks prednisone taper, Part 1: Tocilizumab qw + 26 weeks prednisone taper, Part 2: Open-Label Tocilizumab qw |
| PrednisonePrednisone 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. | Drug | 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 PlaceboTocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study. | Drug | Part 1: Placebo + 26 weeks prednisone taper, Part 1: Placebo + 52 weeks prednisone taper, Part 1: Tocilizumab q2w + 26 weeks prednisone taper |
| Prednisone PlaceboPrednisone 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. | Drug | 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 |
| CorticosteroidsParticipants 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. | Drug | Part 2: Open-Label Tocilizumab qw |
| MethotrexateParticipants 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. | Drug | Part 2: Open-Label Tocilizumab qw |
Primary outcome
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)
Time frame: Week 52
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.
14 secondary outcomes
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)
Time frame: Week 52
Time to First GCA Disease Flare
Time frame: Up to 52 weeks
Total Cumulative Prednisone Dose
Time frame: Up to 52 weeks
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52
Time frame: Baseline, Week 52
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab
Time frame: Baseline and Week 16 (Predose [Hour 0], 24, 48, 72, 96, and 120 or 144 hours postdose); Weeks 1, 2, 17, and 18 (Predose [Hour 0])
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Time frame: Predose (Hour 0) at Baseline and Week 52
Serum Interleukin-6 (IL-6) Level
Time frame: Baseline and Week 52
Serum Soluble IL-6 Receptor (sIL-6R) Level
Time frame: Baseline and Week 52
Erythrocyte Sedimentation Rate (ESR)
Time frame: Baseline and Week 52
C-Reactive Protein (CRP) Level
Time frame: Baseline and Week 52
Percentage of Participants With Anti-Tocilizumab Antibodies
Time frame: Baseline up to Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38279390Stone 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.
- Derived from this study: PubMed 34718434Stone 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.
- Derived from this study: PubMed 34049857Unizony 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.
- Derived from this study: PubMed 30835950Stone 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.
- Derived from this study: PubMed 30786937Strand 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.
- Derived from this study: PubMed 28745999Stone 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.
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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
78 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab, Prednisone and Corticosteroids in people with Giant Cell Arteritis, run by Hoffmann-La Roche at 78 sites in 14 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 3 inclusion and 14 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 6 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Germany, United Kingdom, Italy, France and 9 more countries. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 18 May 2017). 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?
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper) (time frame: Week 52). 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 NCT01791153, which also lists 6 linked publications.
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 6 Feb 2020.