TARGET GCAT Registry

Proposal for Establishment of a UK Post-marketing Surveillance Registry to Study the Effectiveness, Safety and Prescribing Habits of Tocilizumab for the Treatment of Giant Cell Arteritis in the UK National Health Service, Nested Within the Existing Structure of the UK GCA Consortium and UKIVAS Studies

A longitudinal post-marketing surveillance registry nested within the UK GCA Consortium that assesses the effectiveness and safety of tocilizumab in controlling refractory or relapsing forms of GCA in patients who require escalation of therapy to reach sustained remission. Half the patients recruited will have been prescribed tocilizumab (cases) and the other half will be prescribed alternative therapies (controls).

There are four study visits over 18 months: baseline, 6 months, 12 months and 18 months. At each visit data is collected on demographics; diagnosis and investigations; previous and concomitant medications; medical history; co-morbidities, vital signs; smoking and alcohol; disease activity and damage; routine laboratory tests; reason for starting escalation therapy. Safety data is collected on an ongoing basis.

Study Overview

• Status: Terminated
• Conditions: Giant Cell Arteritis

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust
  • Cambridge, United Kingdom
    • Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust
  • Derby, United Kingdom
    • Royal Derby Hospital, University Hospital of Derby and Burton NHS Foundation Trust
  • Dundee, United Kingdom
    • Ninewells Hospital and Medical School, NHS Tayside
  • Edinburgh, United Kingdom
    • NHS Lothian, Edinburgh
  • Glasgow, United Kingdom
    • Inverclyde Royal Hospital, NHS Greater Glasgow & Clyde
  • Glasgow, United Kingdom
    • Royal Alexandra Hospital, NHS Greater Glasgow & Clyde
  • Glasgow, United Kingdom
    • Vale of Leven Hospital, NHS Greater Glasgow & Clyde
  • Harrogate, United Kingdom
    • Harrogate and District NHS Foundation Trust
  • Keighley, United Kingdom
    • Airedale General Hospital, Airedale NHS Foundation Trust
  • Kendal, United Kingdom
    • Royal Lancaster & Westmorland General, University Hospitals of Morecambe Bay NHS Foundation Trust
  • Leeds, United Kingdom
    • Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Foundation Trust
  • Leicester, United Kingdom
    • Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust
  • Liverpool, United Kingdom
    • Aintree University Hospital, Aintree University Hospital NHS Foundation Trust
  • Llantrisant, United Kingdom
    • Royal Glamorgan Hospital, Cwm Taf University Health Board
  • London, United Kingdom
    • Kings College Hospital NHS Foundation Trust
  • London, United Kingdom
    • Royal Free Hospital, Royal Free London NHS Foundation Trust
  • London, United Kingdom
    • University College London NHS Foundation Trust
  • Luton, United Kingdom
    • Luton and Dunstable Hospital, The Luton and Dunstable Hospitals NHS Foundation Trust
  • Manchester, United Kingdom
    • Manchester Royal Infirmary, Central Manchester University Hospitals NHS Foundation Trust
  • Newcastle Upon Tyne, United Kingdom
    • The Freeman Hospital, The Newcastle-upon-Tyne Hospitals NHS Foundation Trust
  • Northampton, United Kingdom
    • Northampton General Hospital
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital Nhs Foundation Trust
  • Nottingham, United Kingdom
    • Queens Medical Centre, Nottingham University Hospitals NHS Trust
  • Oxford, United Kingdom
    • Oxford Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust
  • Preston, United Kingdom
    • Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust
  • Southend-on-Sea, United Kingdom
    • Southend University Hospital NHS Foundation Trust
  • Stevenage, United Kingdom
    • Lister Hospital, East and North Hertfordshire NHS Trust
  • Torquay, United Kingdom
    • Torbay Hospital, Torbay and South Devon NHS Foundation Trust
  • Truro, United Kingdom
    • Royal Cornwall Hospitals NHS Foundation Trust
  • Wakefield, United Kingdom
    • Dewsbury & District Hospital, Mid Yorkshire Hospitals NHS Trust
  • Wakefield, United Kingdom
    • Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust
  • Wishaw, United Kingdom
    • University Hospital Wishaw, NHS Lanarkshire
  • York, United Kingdom
    • York Teaching Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

500 patients prescribed tocilizumab for GCA within the NHS and 500 age-, sex- and centre-matched controls.

Description

Inclusion Criteria:

• Patient must have a diagnosis of GCA and be eligible for the UK GCA Consortium study
• Willing and able to consent
• Have refractory or relapsing GCA as defined by the NHS England commissioning statement for tocilizumab.
• Require treatment escalation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case; Cases are patients that are prescribed tocilizumab as escalation therapy for relapsing/refractory GCA
Control; Controls are those that are prescribed an alternative escalation therapy (not tocilizumab) for relapsing/refractory GCA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the proportion of eligible patients who achieve sustained partial or complete remission 6 months after the start of tocilizumab	Data on disease features and lab tests collected at 6 month, compared with that collected at baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the proportion of eligible patients who achieve a sustained complete remission 6 months after the start of tocilizumab	Data on disease features and lab tests collected at 6 month, compared with that collected at baseline	6 months
To assess the safety (event reporting) and effectiveness (in terms of prevention of relapse) of tocilizumab compared to other strategies for refractory/relapsing disease in patients with GCA who require escalation therapy.	Collection of safety data throughout study (non serious adverse events, serious adverse events, adverse events of special interest, special situations, notification of death)	18 months
To compare characteristics (demographics, disease severity, risk factors for steroid toxicity, contraindications to tocilizumab, concomitant medications) of real-world patients prescribed tocilizumab to clinical trial populations.	All data collected throughout the study period	0-18 months
To describe relapse rates in patients with GCA treated with tocilizumab at treatment completion (usually 12 months in the UK) and 6 months following discontinuation of tocilizumab	Data on disease features and lab tests collected at month 12 and 18 and compared with that collected at baseline and month 6	0-18 months
To describe disease activity during the first 6 and 12 months following the start of tocilizumab, compared to other treatment strategies for refractory/relapsing disease	Data collected on disease features, inflammatory markers and vital signs.	0-12 months
To describe ischaemic complications during the first 6 and 12 months following the start of tocilizumab, compared to other treatment strategies for refractory/relapsing disease	Data collected on disease features and event reporting as appropriate (serious adverse events & non-serious adverse events).	0-12 months
To describe drug related toxicity during the first 6 and 12 months following the start of tocilizumab, compared to other treatment strategies for refractory/relapsing disease	Data collected on lab results such as HbA1c and medication taken including the dose, reason for changes in dose or discontinuation, documentation of any events relating to drug toxicity.	0-12 months
To describe patterns of glucocorticoid dosing, including estimated cumulative dose & time to discontinuation of glucocorticoids, in patients with GCA & treated with tocilizumab, compared to other treatment strategies for refractory/relapsing disease	Data on glucocorticoid collected throughout study including dose changes & date of change	0-18 months
To describe reasons for premature discontinuation of tocilizumab	Reason for premature discontinuation of tocilizumab is captured at the follow up visits.	0-18 months
To estimate the prevalence of glucocorticoid toxicity (e.g. weight gain, fracture, diabetes, infection, or new psychiatric diagnosis) in patients with GCA who are treated with tocilizumab, compared to other strategies for refractory/relapsing disease	Data collected throughout study on features associated with glucocorticoid toxicity such as those listed within the title	0-18 months
To invite patients who agree to take part in the current study to consent to being approached to participate in future related studies of their condition, including randomised controlled trials	Keeping a record of those who have been agreed to be contacted for similar studies in the randomised controlled trials	0-18 months

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: Hoffmann-La Roche; University of Oxford
• Investigators: Principal Investigator: Ann Morgan, University of Leeds

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: August 5, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 12, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Tocilizumab; Giant Cell Arteritis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis
• Other Study ID Numbers: MM05/7307

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No