TocILizumab in aorTitis in GCA (TILT)

NCT06271018 | Recruiting

• 1 other identifier: GMIO-2024-0001
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a french multicenter observational study assessing safety and efficacy of biosimilar of Tocilizumab in Giant Cell Arteritis (GCA) with active aortitis, including 14 reference centers from the Groupe d'Etude Français des vascularites des gros vaisseaux (GEFA). Giant Cell Arteritis (GCA), formerly known as temporal arteritis, is the most common form of systemic vasculitis in patients aged ≥ 50 years. GCA is defined by granulomatous arteritis that affects large#sized and medium#sized blood vessels with a predisposition to affect the cranial arteries. Aortitis accounted for more than 50% of GCA patients with the new imaging techniques. Aortitis is typically diagnosed using imaging tests such as magnetic resonance imaging (MRI) or Computed Tomography (CT) scans. Aortitis is an inflammation of the aorta, leading to a range of symptoms such as fever, weight loss, fatigue, and chest pain. In severe cases, aortic aneurysms or aortic dissection can occur, which can be life-threatening. Multiple reports have demonstrated the presence of abnormal pro-inflammatory cytokine production in large-vessel vasculitis patients, particularly those with GCA, including interleukin-1 (IL-1), IL-6, IL-18, tumor necrosis factor-α (TNF-α), and interferon-γ, by T lymphocytes and macrophages. IL-6 has been implicated as a crucial cytokine in the pathogenesis of aortitis and targeting its signaling has shown promising results in treating the condition. IL-6 inhibitors such as tocilizumab have been found to effectively reduce disease activity and improve clinical outcomes in GCA patients. The GIACTA study (GiAnt cell arteritis roActemra (tocilizumab) study) was a randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of tocilizumab in the treatment of GCA. The study included 251 patients with newly diagnosed or relapsing GCA and found that treatment with tocilizumab significantly increased the proportion of patients who achieved sustained remission from GCA at 52 weeks, compared to placebo. Additionally, tocilizumab was associated with a lower incidence of disease flares and a reduced need for glucocorticoid therapy. Following the positive results of the GIACTA study, tocilizumab was approved for the treatment of GCA in adults with active disease, including aortitis, who have not responded to glucocorticoids, or for whom glucocorticoid therapy is not appropriate, by regulatory agencies around the world, including the US Food and Drug Administration and the European Medicines Agency. However, the efficacy of IL-6 inhibitors on aorta inflammation as assessed by modern and powerful imaging techniques has never been specifically studied in GCA. This observational study will provide important informations on the impact of Tyenne® (tocilizumab) associated with short term low dose steroids on clinical manifestations and vessel inflammation and damage in aortitis of GCA.

Conditions

Aortitis; Giant Cell Arteritis (GCA)

Keywords

Giant Cell Arteritis (GCA); Aortitis; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• To evaluate the proportion of patients with remission of GCA

  Proportion of patients with remission of GCA at week 24. EULAR consensus definitions for remission in GCA and other types of LVV is defined as the absence of all clinical signs and symptoms attributable to active LVV, normalization of ESR and CRP values, and no evidence of progressive aortic damage at angio CT and Tep FDG.

  week 24

Secondary Outcomes (6)

• To assess the cumulative incidence of relapse

  Weeks 12, 24, 36 , 52 and 104

• To assess the proportion of GCA in remission (according to EULAR consensus definitions) after treatment start

  Weeks 12, 24, 36 , 52 and 104

• To assess the cumulative dose of prednisone

  Weeks 12, 24, 36, 52 and 104

• To assess the cumulative incidence of severe adverse events

  Weeks 12, 24, 36, 52 and 104

• To assess the proportion of radiological vascular progression

  Weeks 12, 24, 36 , 52 and 104

Study Arms (1)

Aortitis in GCA

Adult patients with active aortitis associated with GCA, requiring treatment with Tocilizumab biosimilar used within the scope of its market authorization (standard of care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients with active aortitis associated with GCA, requiring treatment with Tocilizumab biosimilar within the scope of its market authorization (standard of care)

You may qualify if:

• Patients ≥18 years
• Signed informed consent
• Affiliation with the French national social security system
• Adequate and effective contraceptive measures
• For women of childbearing age, a negative serum pregnancy test.
• Diagnosis of GCA according to 2022 ACR/EULAR criteria
• Active newly diagnosed or relapsing Aortitis related to GCA proved by imaging (Tep-scan, angio-CT or magnetic resonance imaging angiography)
• No neoplasia
• No contraindication to Tocilizumab

You may not qualify if:

• Pregnancy or breastfeeding ;
• History of severe immunosuppression, HIV or HBsAg positive
• Non response or intolerance to previous therapy with tocilizumab
• Positive QuantiFERON test result (QFT-TBGIn-Tube)
• Have received live vaccines within 3 months prior to the start of the trial
• History of malignancy in the last 5 years
• Severe renal impairment (creatinine clearance \<30mL/min/1.73m²)
• Liver dysfunction defined as aspartate transaminase (AST) or alanine transaminase (ALT) levels ≥ 5 at the upper limit of normal
• Blood count abnormality:
• Platelet count \< 50 x 10.3/mm3
• Neutropenia \< 1000/mm3
• Hemoglobin \< 8 g/dl

Sponsors & Collaborators

• Groupe français d'étude des Maladies Inflammatoires de loeil: lead

Study Sites (1)

Département de Medecine interne et d'immunologie clinique - hôpital La Pitié Salpetrière

Paris, 75013, France

RECRUITING

Related Publications (3)

• Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, Butikofer L, Seitz M, Reichenbach S. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016 May 7;387(10031):1921-7. doi: 10.1016/S0140-6736(16)00560-2. Epub 2016 Mar 4.

  PMID: 26952547 RESULT

• 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: 28745999 RESULT

• Hellmich B, Agueda A, Monti S, Buttgereit F, de Boysson H, Brouwer E, Cassie R, Cid MC, Dasgupta B, Dejaco C, Hatemi G, Hollinger N, Mahr A, Mollan SP, Mukhtyar C, Ponte C, Salvarani C, Sivakumar R, Tian X, Tomasson G, Turesson C, Schmidt W, Villiger PM, Watts R, Young C, Luqmani RA. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79(1):19-30. doi: 10.1136/annrheumdis-2019-215672. Epub 2019 Jul 3.

  PMID: 31270110 RESULT

MeSH Terms

Conditions

Aortitis; Giant Cell Arteritis

Condition Hierarchy (Ancestors)

Aortic Diseases; Vascular Diseases; Cardiovascular Diseases; Vasculitis; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Arteritis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

David SAADOUN, Professor

CONTACT

+33142178042; david.saadoun@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: February 21, 2024
• Study Start: March 27, 2024
• Primary Completion (Estimated): September 27, 2026
• Study Completion (Estimated): March 27, 2028
• Last Updated: December 20, 2024

Record last verified: 2024-12

Locations

FR (1)