NCT06957002

Bosentan in the Treatment of Giant Cell Arteritis

Bosentan in the Treatment of Giant Cell Arteritis. Multicenter, Randomized, Controlled, Superiority Phase II Trial Comparing a Combination of Bosentan and Glucocorticoids Versus Glucocorticoids Alone in the Treatment of Patients With GCA

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 50 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether a treatment with 3 months of bosentan associated to standard therapy might be superior to glucocorticoids alone in term of failure free survival at 12 months

Detailed description

Giant cell arteritis (GCA) is the most common vasculitis in individuals over the age of 50. It is characterized by inflammation of large vessels, including the aorta and its main branches. Patients experience headaches, scalp tenderness, joint pain, and general symptoms such as weight loss, fatigue, and fever. More rarely, unilateral or bilateral visual acuity is impaired. At the biological level, an increase in inflammatory markers, such as C-reactive protein (CRP), is observed. Glucocorticoids (GCs) are the cornerstone of GCA treatment and are usually administered for 12 to 18 months to prevent relapse, sometimes longer. However, most patients develop significant adverse effects associated with GCs, including hypertension, arterial disease, diabetes, osteoporosis, and infections. As a result, various strategies targeting the inflammatory process have been developed to reduce GC use. For example, methotrexate has been shown to be a modestly effective GC-sparing treatment. A 12-month course of tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has also been shown to induce and maintain remission of GCA, with a significant GC-sparing effect. However, only 45% of patients remained in long-term remission after discontinuing tocilizumab. In patients with GCA, in addition to lymphocyte (white blood cell) activation, the investigator observed increased proliferative properties of vascular smooth muscle cells (VSMCs), obtained from temporal artery biopsies at the time of diagnosis. This proliferation and migration of VSMCs are promoted by endothelin-1 (ET-1), a molecule expressed in the walls of diseased arteries. Thus, ET-1 contributes to vessel lumen narrowing and complete obstruction. It was found that plasma ET-1 concentrations were higher in patients with visual ischemic complications. Additionally, an association was found between endothelin expression in temporal artery biopsies at baseline and therapeutic response at month six. Bosentan has been marketed since 2002 for the management of patients with pulmonary arterial hypertension. This vasodilating drug is an endothelin (ET-1) receptor antagonist. The investigator hypothesize that a 3-month course of treatment with bosentan, an endothelin receptor antagonist, combined with standard therapy, could be more effective than glucocorticoids (GCs) alone, reducing the risk of relapse and the current adverse effects, thereby improving relapse-free survival at 12 months.

Conditions

• Giant Cell Arteritis (GCA)

Interventions

Type	Name	Description
DRUG	Bosentan	Bosentan : 62.5 mg twice a day for 4 weeks and 125 mg twice a day during 9 weeks (treatment length 3 months)
DRUG	Glucocorticoids	prespecified GC tapering schedule

Timeline

• Start date: 2025-09-01
• Primary completion: 2029-09-01
• Completion: 2029-09-01
• First posted: 2025-05-04
• Last updated: 2025-05-14

Locations

1 site across 1 country: France