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

Primary Purpose

Giant Cell Arteritis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tocilizumab
Prednisone
Tocilizumab Placebo
Prednisone Placebo
Corticosteroids
Methotrexate
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Giant Cell Arteritis

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Univ of Calif., Los Angeles; Rheumatology
  • Cedars-Sinai Medical Center
  • Rheumatology Assoc. of S. Florida - Clinical Research Center
  • Sarasota Arthritis Res Center
  • Four Rivers Clinical Research Inc.
  • Rheumatology Associates
  • Massachusetts General Hospital
  • Shores Rheumatology
  • Mayo Clinic Rochester
  • Hospital For Special Surgery; Dept of Medicine - Rheumatology
  • Asheville Arthritis & Osteoporosis Center, PA
  • University of Pennsylvania
  • University of Utah; Division of Rheumatology
  • Marshfield Clinic Wausau Ctr
  • Hospital Erasme
  • UZ Leuven Gasthuisberg
  • Clin. de Rhumatologie
  • Nordsjællands Hospital - Hillerød;Department of Rheumatology 0731
  • Hopital Avicenne; Medecine Interne H5
  • Hopital La Cavale Blanche; Rhumatologie
  • Hopital Claude Huriez; Internal Medicine
  • Hôpital de la Conception
  • Hopital Emile Muller; Medecine Interne
  • Hopital Cochin; Medecine Interne
  • Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
  • Rheuma-Klinikum Bad Bramstedt Klinik fuer Rheumatologie und Immunologie
  • Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie
  • Schlosspark Klinik; Abt. Rheumatologie
  • Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
  • Universitätsklinikum Erlangen; Medizinische Klinik 3; Rheumatologie und Immunologie
  • Universitätsklinikum Freiburg
  • Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie
  • Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie
  • Universitätsklinikum Jena; Klinik für Innere Medizin III
  • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
  • Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
  • Kreiskliniken Esslingen gGmbH Klinik Plochingen Medizinische Klinik
  • Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
  • Arcispedale Santa Maria Nuova; Reumatologia
  • Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia
  • Università Degli Studi Di Genova - Dimi; Reumatologia
  • Irccs San Raffele; Div Med Gen Immunologia Clinica
  • A.O. Universitaria Pisana; Psichiatria
  • Azienda Ospedaliera di Padova; Cattedra e Divisione di Reumatologia
  • Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
  • VU Medisch Centrum; Reumatologie 4-A-A2
  • Ziekenhuis Rijnstate
  • Universitair Medisch Centrum Groningen
  • Ziekenhuisgroep Twente, Hengelo
  • Akademisch Ziekenhuis St. Radboud; Rheumatology
  • Sørlandet Sykehus Kristiansand
  • Rikshospitalet; Revmatologisk Avd Seksjon Barnerevmatologi
  • Ålesund sjukehus
  • Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
  • Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Hospital Geral de Santo Antonio; Servico de Imunologia Clinica
  • Hospital Univ A Coruna; Rheumatology
  • Hospital Universitario de Canarias;servicio de Reumatologia
  • Hospital de Basurto; Servicio de Reumatologia
  • Hospital Universitari de Bellvitge; Servicio de Reumatologia
  • University of Barcelona; Dept. of Internal Medicine,
  • Sahlgrenska Universitetssjukhuset
  • Skånes Universitetssjukhus
  • Skånes Universitetssjukhus Malmö; Reumatologkliniken
  • Karolinska Sjukhuset; Reumatologkliniken D2-1
  • Akademiska Sjukhuset; Lungmedicinska Kliniken
  • Aberdeen Royal Infirmary; Medical Oncology Dept
  • Barnsley General Hospital; Rheumatology
  • Old Queen Elizabeth Hospital; Pharmacy Building;Clinical Research offices
  • Colchester General Hospital; Aseptic Dept, Pharmacy Support Unit
  • University of Edinburgh; The Queens Medical Research Institute
  • CHAPEL ALLERTON HOSPITAL; Unit of Musculoskeletal Disease
  • Moorfields Eye Hospital NHS Foundation Trust
  • Freeman Hospital; Dept of Rheumatology
  • Queen's Hospital
  • Haywood Hospital; Staffordshire Rheumatology Centre
  • Royal Cornwall Hospital; Rhuematololgy Dept
  • Southend Hospital; Rheumatology Department

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Experimental

Arm Label

Part 1: Tocilizumab qw + 26 weeks prednisone taper

Part 1: Tocilizumab q2w + 26 weeks prednisone taper

Part 1: Placebo + 26 weeks prednisone taper

Part 1: Placebo + 52 weeks prednisone taper

Part 2: Open-Label Tocilizumab qw

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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).
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).
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.
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.
Serum Interleukin-6 (IL-6) Level
Serum Soluble IL-6 Receptor (sIL-6R) Level
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.
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.
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.

Full Information

First Posted
February 12, 2013
Last Updated
February 4, 2020
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT01791153
Brief Title
An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
July 22, 2013 (Actual)
Primary Completion Date
April 11, 2016 (Actual)
Study Completion Date
June 4, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Giant Cell Arteritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
251 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Tocilizumab qw + 26 weeks prednisone taper
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1: Tocilizumab q2w + 26 weeks prednisone taper
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1: Placebo + 26 weeks prednisone taper
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Part 1: Placebo + 52 weeks prednisone taper
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Part 2: Open-Label Tocilizumab qw
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tocilizumab
Other Intervention Name(s)
RoActemra, Actemra, RO4877533
Intervention Description
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
Intervention Name(s)
Prednisone
Intervention Description
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
Intervention Name(s)
Tocilizumab Placebo
Intervention Description
Tocilizumab placebo will be administered as SC injection qw or q2w for 52 weeks in Part 1 of the study.
Intervention Type
Drug
Intervention Name(s)
Prednisone Placebo
Intervention Description
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
Intervention Name(s)
Corticosteroids
Intervention Description
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
Intervention Name(s)
Methotrexate
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 26 Weeks Prednisone Taper)
Description
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.
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Percentage of Participants in Sustained Remission at Week 52 (Tocilizumab + 26 Weeks Prednisone Taper Versus Placebo + 52 Weeks Prednisone Taper)
Description
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.
Time Frame
Week 52
Title
Time to First GCA Disease Flare
Description
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.
Time Frame
Up to 52 weeks
Title
Total Cumulative Prednisone Dose
Description
The median total cumulative prednisone dose over the 52 weeks for each treatment group and the corresponding 95% confidence intervals are presented.
Time Frame
Up to 52 weeks
Title
Change From Baseline in Short Form (SF)-36 Questionnaire Score at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity Assessed Using Visual Analogue Scale (VAS) at Week 52
Description
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.
Time Frame
Baseline, Week 52
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) at Steady State of Tocilizumab
Description
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).
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])
Title
Maximum Serum Concentration at Steady State (Cmax,ss) of Tocilizumab
Description
Cmax,ss is maximum model-predicted serum steady state concentration of tocilizumab measured in micrograms per milliliter (mcg/mL).
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])
Title
Minimum Serum Concentration at Steady State (Cmin,ss) of Tocilizumab
Description
Cmin,ss is minimum model-predicted serum steady state concentration of tocilizumab measured in mcg/mL.
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])
Title
Minimum Observed Serum Concentration (Ctrough) of Tocilizumab
Description
Ctrough is minimum observed serum concentration of tocilizumab measured in mcg/mL.
Time Frame
Predose (Hour 0) at Baseline and Week 52
Title
Serum Interleukin-6 (IL-6) Level
Time Frame
Baseline and Week 52
Title
Serum Soluble IL-6 Receptor (sIL-6R) Level
Time Frame
Baseline and Week 52
Title
Erythrocyte Sedimentation Rate (ESR)
Description
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.
Time Frame
Baseline and Week 52
Title
C-Reactive Protein (CRP) Level
Description
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.
Time Frame
Baseline and Week 52
Title
Percentage of Participants With Anti-Tocilizumab Antibodies
Description
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.
Time Frame
Baseline up to Week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Univ of Calif., Los Angeles; Rheumatology
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Rheumatology Assoc. of S. Florida - Clinical Research Center
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Sarasota Arthritis Res Center
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34239
Country
United States
Facility Name
Four Rivers Clinical Research Inc.
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42003
Country
United States
Facility Name
Rheumatology Associates
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Shores Rheumatology
City
Saint Clair Shores
State/Province
Michigan
ZIP/Postal Code
48081
Country
United States
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Hospital For Special Surgery; Dept of Medicine - Rheumatology
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Asheville Arthritis & Osteoporosis Center, PA
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Utah; Division of Rheumatology
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Marshfield Clinic Wausau Ctr
City
Wausau
State/Province
Wisconsin
ZIP/Postal Code
54401
Country
United States
Facility Name
Hospital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Clin. de Rhumatologie
City
Trois-rivieres
State/Province
Quebec
ZIP/Postal Code
G8Z 1Y2
Country
Canada
Facility Name
Nordsjællands Hospital - Hillerød;Department of Rheumatology 0731
City
Hillerod
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Hopital Avicenne; Medecine Interne H5
City
Bobigny
ZIP/Postal Code
93009
Country
France
Facility Name
Hopital La Cavale Blanche; Rhumatologie
City
Brest
ZIP/Postal Code
29609
Country
France
Facility Name
Hopital Claude Huriez; Internal Medicine
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital de la Conception
City
Marseille
ZIP/Postal Code
13000
Country
France
Facility Name
Hopital Emile Muller; Medecine Interne
City
Mulhouse
ZIP/Postal Code
68070
Country
France
Facility Name
Hopital Cochin; Medecine Interne
City
Paris
ZIP/Postal Code
75679
Country
France
Facility Name
Asklepios Kllinikum Bad Abbach; Klinik für Rheumatologie und Klinische Immunologie
City
Bad Abbach
ZIP/Postal Code
93077
Country
Germany
Facility Name
Rheuma-Klinikum Bad Bramstedt Klinik fuer Rheumatologie und Immunologie
City
Bad Bramstedt
ZIP/Postal Code
24576
Country
Germany
Facility Name
Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Schlosspark Klinik; Abt. Rheumatologie
City
Berlin
ZIP/Postal Code
14059
Country
Germany
Facility Name
Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik III
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Universitätsklinikum Erlangen; Medizinische Klinik 3; Rheumatologie und Immunologie
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Medizinische Hochschule Zentrum Innere Medizin Abt.Klinische Immunologie und Rheumatologie
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Rheumazentrum-Ruhrgebiet, St. Josefs-Krankenhaus; Rheumatologie
City
Herne
ZIP/Postal Code
44652
Country
Germany
Facility Name
Universitätsklinikum Jena; Klinik für Innere Medizin III
City
Jena
ZIP/Postal Code
07747
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Klinikum der Universitat Munchen; Bereich Pettenkoferstr; Rheumaeinheit der medizinischen Klinik IV
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Kreiskliniken Esslingen gGmbH Klinik Plochingen Medizinische Klinik
City
Plochingen
ZIP/Postal Code
73207
Country
Germany
Facility Name
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Arcispedale Santa Maria Nuova; Reumatologia
City
Reggio Emilia
State/Province
Emilia-Romagna
ZIP/Postal Code
42100
Country
Italy
Facility Name
Policlinico Univ. Uni Degli Sudi Di Udine; Clinica Di Reumatologia
City
Udine
State/Province
Friuli-Venezia Giulia
ZIP/Postal Code
33100
Country
Italy
Facility Name
Università Degli Studi Di Genova - Dimi; Reumatologia
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
Irccs San Raffele; Div Med Gen Immunologia Clinica
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
A.O. Universitaria Pisana; Psichiatria
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
Azienda Ospedaliera di Padova; Cattedra e Divisione di Reumatologia
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Azienda Ospedaliera di Verona-Ospedale Civile Maggiore
City
Verona
State/Province
Veneto
ZIP/Postal Code
37126
Country
Italy
Facility Name
VU Medisch Centrum; Reumatologie 4-A-A2
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Ziekenhuis Rijnstate
City
Arnhem
ZIP/Postal Code
6815 AD
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Ziekenhuisgroep Twente, Hengelo
City
Hengelo
ZIP/Postal Code
7555 DL
Country
Netherlands
Facility Name
Akademisch Ziekenhuis St. Radboud; Rheumatology
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Sørlandet Sykehus Kristiansand
City
Kristiansand
ZIP/Postal Code
4604
Country
Norway
Facility Name
Rikshospitalet; Revmatologisk Avd Seksjon Barnerevmatologi
City
Oslo
ZIP/Postal Code
0027
Country
Norway
Facility Name
Ålesund sjukehus
City
Ålesund
ZIP/Postal Code
N-6026
Country
Norway
Facility Name
Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Klinika Reumatologii I Chorób Wewn. Pum W Szczecinie; Samodzielny Publiczny Szpital Kliniczny Nr 1
City
Szczecin
ZIP/Postal Code
71-252
Country
Poland
Facility Name
Hospital Geral de Santo Antonio; Servico de Imunologia Clinica
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
Hospital Univ A Coruna; Rheumatology
City
A Coruna
State/Province
LA Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario de Canarias;servicio de Reumatologia
City
La Laguna
State/Province
Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Hospital de Basurto; Servicio de Reumatologia
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48013
Country
Spain
Facility Name
Hospital Universitari de Bellvitge; Servicio de Reumatologia
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
University of Barcelona; Dept. of Internal Medicine,
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Sahlgrenska Universitetssjukhuset
City
Goteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Skånes Universitetssjukhus
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Skånes Universitetssjukhus Malmö; Reumatologkliniken
City
Malmo
ZIP/Postal Code
205 02
Country
Sweden
Facility Name
Karolinska Sjukhuset; Reumatologkliniken D2-1
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden
Facility Name
Akademiska Sjukhuset; Lungmedicinska Kliniken
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Aberdeen Royal Infirmary; Medical Oncology Dept
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Barnsley General Hospital; Rheumatology
City
Barnsley
ZIP/Postal Code
S75 2EP
Country
United Kingdom
Facility Name
Old Queen Elizabeth Hospital; Pharmacy Building;Clinical Research offices
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Colchester General Hospital; Aseptic Dept, Pharmacy Support Unit
City
Colchester, Essex
ZIP/Postal Code
CO4 5JL
Country
United Kingdom
Facility Name
University of Edinburgh; The Queens Medical Research Institute
City
Edinburgh
ZIP/Postal Code
EH16 4TJ
Country
United Kingdom
Facility Name
CHAPEL ALLERTON HOSPITAL; Unit of Musculoskeletal Disease
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Facility Name
Freeman Hospital; Dept of Rheumatology
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
Queen's Hospital
City
Romford
ZIP/Postal Code
RM7 0AG
Country
United Kingdom
Facility Name
Haywood Hospital; Staffordshire Rheumatology Centre
City
Stoke-on-trent
ZIP/Postal Code
ST6 7AG
Country
United Kingdom
Facility Name
Royal Cornwall Hospital; Rhuematololgy Dept
City
Truro
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
Facility Name
Southend Hospital; Rheumatology Department
City
Westcliffe-on-sea
ZIP/Postal Code
SS0 0RY
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34718434
Citation
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.
Results Reference
derived
PubMed Identifier
34049857
Citation
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.
Results Reference
derived
PubMed Identifier
30835950
Citation
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.
Results Reference
derived
PubMed Identifier
30786937
Citation
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.
Results Reference
derived
PubMed Identifier
28745999
Citation
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.
Results Reference
derived

Learn more about this trial

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

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