NCT03244709

Brief Summary

Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been found to have a crucial role in the pathogenesis of Giant cel arteritis (GCA). Based on this rationale, several recent studies demonstrated the efficacy of tocilizumab (TCZ), an anti-IL-6 targeted monoclonal antibody, for the treatment of patients with refractory GCA. Confirming previous reports,in a recent retrospective study the investigators successfully treated 10 patient with refractory GCA with TCZ. All patients achieved a complete disease remission evaluated by clinical, laboratory, and positron emission tomography (PET). In a considerable number of GCA patients treated with corticosteroids (CS) the therapy may be interrupted with no disease flares. No data are available on the management of patients achieving the remission with TCZ.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
15

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Jan 2015

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
2.6 years until next milestone

First Submitted

Initial submission to the registry

August 1, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

August 9, 2017

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2017

Completed
Last Updated

August 10, 2017

Status Verified

August 1, 2017

Enrollment Period

3 years

First QC Date

August 1, 2017

Last Update Submit

August 9, 2017

Conditions

Giant Cell Arteritis

Keywords

Giant cell arteritis,TocilizumabAortitisRemission

Outcome Measures

Primary Outcomes (1)

  • The percentage of patients maintaining the off-therapy clinical remission over the follow-up as expressed by absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination

    ESR ≤15 mm/h; CRP ≤0.5 mg/dl; VAS pain ≤10; PET: normalized SUVmax ≤1

    6-month off-therapy period

Secondary Outcomes (3)

  • The percentage of patients achieving and maintaining the clinical remission during the treatment with TCZ as expressed by the absence of GCA symptoms and signs, normal ESR and CRP values, absence of arterial wall inflammation at PET examination

    12 months

  • To compare the role of acute-phase reactants and 18F-FDG-PET in the evaluation of remission.

    Months 6,12,18

  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0" MeDRA 12.1.

    Month 18

Study Arms (1)

Patients with GCA (ACR 1990 criteria)

EXPERIMENTAL

At diagnosis, all GCA patients with or without involvement of aorta and its thoracic branches will receive PDN 50 mg/day and TCZ 8 mg/Kg/iv monthly. In all patients PDN dose will be reduced of 10 mg every 2 weeks until interruption at week 12. Week 12. Subcutaneous TCZ 162 mg/weekly will be administered for additional 12 weeks. Week 24. TCZ tapering every 8 weeks as follows: * 1 injection every 2 weeks * 1 injection every 3 weeks * 1 injection every 4 weeks Week 48. TCZ withdrawal. Week 72. Remission evaluation.

Drug: Tocilizumab

Interventions

TocilizumabDRUG

Intravenous Tocilizumab followed by subcutaneousTocilizumab

Patients with GCA (ACR 1990 criteria)

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- All consecutive patients meeting the 1990 ACR classification criteria for GCA.

You may not qualify if:

  • Corticosteroid treatment during the previous 6 months.
  • Uncontrolled diabetes.
  • Uncontrolled hypertension.
  • History of cancer within the past 5 years.
  • History of frequent infections in the past.
  • Positivity of screening procedures for latent tuberculosis infection.
  • Uncontrolled dyslipidemia at baseline.
  • Known intestinal diverticulosis.
  • Concomitant hematologic disorders.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fabrizio Cantini

Prato, Tuscany, 59100, Italy

RECRUITING

Related Publications (6)

  • Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008 Jul 19;372(9634):234-45. doi: 10.1016/S0140-6736(08)61077-6.

    PMID: 18640460BACKGROUND

  • Soussan M, Nicolas P, Schramm C, Katsahian S, Pop G, Fain O, Mekinian A. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine (Baltimore). 2015 Apr;94(14):e622. doi: 10.1097/MD.0000000000000622.

    PMID: 25860208BACKGROUND

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

    PMID: 28745999BACKGROUND

  • Unizony S, Arias-Urdaneta L, Miloslavsky E, Arvikar S, Khosroshahi A, Keroack B, Stone JR, Stone JH. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res (Hoboken). 2012 Nov;64(11):1720-9. doi: 10.1002/acr.21750.

    PMID: 22674883RESULT

  • Loricera J, Blanco R, Hernandez JL, Castaneda S, Mera A, Perez-Pampin E, Peiro E, Humbria A, Calvo-Alen J, Aurrecoechea E, Narvaez J, Sanchez-Andrade A, Vela P, Diez E, Mata C, Lluch P, Moll C, Hernandez I, Calvo-Rio V, Ortiz-Sanjuan F, Gonzalez-Vela C, Pina T, Gonzalez-Gay MA. Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients. Semin Arthritis Rheum. 2015 Jun;44(6):717-23. doi: 10.1016/j.semarthrit.2014.12.005. Epub 2014 Dec 27.

    PMID: 25697557RESULT

  • Proven A, Gabriel SE, Orces C, O'Fallon WM, Hunder GG. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum. 2003 Oct 15;49(5):703-8. doi: 10.1002/art.11388.

    PMID: 14558057RESULT

MeSH Terms

Conditions

Giant Cell ArteritisAortitis

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous SystemAutoimmune Diseases of the Nervous SystemNervous System DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesVascular DiseasesCardiovascular DiseasesArteritisVasculitisSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesAortic Diseases

Study Design

Study Type
interventional
Phase
phase 4
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of the Dpt. of Rheumatology

Study Record Dates

First Submitted

August 1, 2017

First Posted

August 9, 2017

Study Start

January 1, 2015

Primary Completion

December 31, 2017

Study Completion

December 31, 2017

Last Updated

August 10, 2017

Record last verified: 2017-08

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)