Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission.

Giant Cell Arteritis Clinical Trial

Official title:

Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission: a Prospective, Pilot Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03244709
• Other study ID #: Hospital of Prato, Italy
• Status: Recruiting
• Phase: Phase 4
• First received: August 1, 2017
• Last updated: August 9, 2017
• Start date: January 1, 2015
• Est. completion date: December 31, 2017

Study information

• Verified date: August 2017
• Source: Hospital of Prato
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study design. Open-label, prospective, pilot study on patients with giant cell arteritis (GCA) resistant to corticosteroids (CS) .

Setting. Rheumatology department, Hospital of Prato, Prato, Italy. Treatment. All refractory GCA patients with or without involvement of aorta and its thoracic branches treated with intravenous TCZ at the dose of 8 mg/Kg/monthly or subcutaneous TCZ at the dose of 162 mg/weekly who achieved a stable remission over a 6-month period should receive reduced TCZ doses with the following schedules: intravenous TCZ tapering to 2 mg/Kg/monthly with drug withdrawal at month 4, and subcutaneous TCZ monthly reduction through the lengthening of injection intervals every 2, 3 , and 4 weeks, and with drug interruption at month 4.

Primary end-point. To investigate the maintenance of clinical remission after TCZ interruption over a 6-month follow-up period.

Secondary end-points. To assess the maintenance of clinical remission during the treatment, to evaluate the role of acute-phase reactants and PET in predicting the relapse and remission, and to assess the occurrence of adverse event (AEs).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

Drug:
• Tocilizumab
Intravenous Tocilizumab followed by subcutaneousTocilizumab

Locations

Country	Name	City	State
Italy	Fabrizio Cantini	Prato	Tuscany

Sponsors (1)

Lead Sponsor	Collaborator
Hospital of Prato

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Loricera J, Blanco R, Hernández JL, Castañeda S, Mera A, Pérez-Pampín E, Peiró E, Humbría A, Calvo-Alén J, Aurrecoechea E, Narváez J, Sánchez-Andrade A, Vela P, Díez E, Mata C, Lluch P, Moll C, Hernández Í, Calvo-Río V, Ortiz-Sanjuán F, González-Vela C, P — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View 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. — View Citation

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 (Hoboke — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Absence of GCA symptoms and signs, ESR =15 mm/h, CRP =0.5 mg/dL, PET: normalized SUVmax =1	12 months
Secondary	To compare the role of acute-phase reactants and 18F-FDG-PET in the evaluation of remission.	Linear regression analysis for the correlation between ESR and CRP values and nSUVmax at baseline and after therapy	Months 6,12,18
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0" MeDRA 12.1.	Overall AEs and serious AEs will be recorded	Month 18