Bosentan in the treatment of Giant Cell Arteritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2025-08-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Ministry of Health National PHRC 2019.

External identifiers

EU CT number

2024-517030-17-00

ClinicalTrials.gov

NCT06957002

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the benefit of an additional 3 months of bosentan therapy in patients treated by GC for a new or relapsing GCA, after 52 weeks of follow-up

Secondary objectives 9

1. 1) To compare the occurrence of new ischemic event
2. 2) To compare (bosentan versus reference group) the proportion of patients in remission without prednisone at W52
3. 3) To compare (bosentan versus reference group) the proportion of patients in remission with ≤5 mg/day of prednisone at W52
4. 4) To assess the GC-sparing effect of bosentan in the treatment of GCA
5. 5) To assess the effect of bosentan on quality of life
6. 6) To compare the proportion of patients in remission at year 2 and the relapse rate from year 1 to year 2
7. 7) To compare the number of patients still receiving GC at year 2
8. 1)To assess the safety of bosentan in the treatment of GCA
9. 2) To assess the effect of bosentan on the frequency of GC­related side effects

Conditions and MedDRA coding

Newly diagnosed or relapsing Giant-cell arteritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. • Patients having given their written informed consent prior to participation in the study.
2. • Patients affiliated with social security or CMU (profit or being entitled)
3. • Diagnosis of GCA, as defined by the revised GCA diagnosis criteria. Patients must satisfy criteria 1-2-3 and 4 (irrespective of time): 1. Age ≥50 years at disease onset 2. History of erythrocyte sedimentation rate (ESR) ≥ 50 mm/h or CRP ≥ 20 mg/L (not mandatory if TAB is positive: see below) 3. At least one of the following: - unequivocal cranial symptoms of GCA (new onset headache, scalp tenderness, jaw claudication, temporal artery abnormality, ischemia-related vision loss) - unequivocal symptoms of polymyalgia rheumatica (PMR) 4. At least one of the following: - Temporal artery biopsy (TAB) compatible with the diagnosis of GCA (non-necrotizing vasculitis with a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells) - Evidence of large vessel vasculitis: o angio-CT or angio-MRI: thickened and/or contrast-enhanced arteries especially aorta (≥2mm) and epiaortic arteries (≥1mm) and contrast enhanced arteries in T1-weighted sequences o or PET scan: ≥ grade 2 (from 0 to 3) tracer uptake on large arteries
4. • At least a sign of active GCA within the 4 weeks prior to randomisation. Active GCA is defined by ESR ≥30 mm/h or CRP ≥10 mg/L and at least one of the following: o unequivocal cranial symptoms of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) o unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness o other features judged by the clinical investigator to be consistent with GCA or PMR flares
5. • Menopausal women (no gynaecological cycle over the past two years), or women who had a gynaecological cycle within previous 24 months (non-menopausal women) only if they have (1) an effective non hormonal contraceptive method throughout study and (2) a negative urinary beta-hCG test at inclusion.

Exclusion criteria 16

1. • Patients under maintenance of justice, wardship or legal guardianship
2. • Patient unable to give written informed consent prior to participation in the study
3. • Patients included in other investigational therapeutic study within the previous 3 months
4. • Patients suspected not to be observant to the proposed treatments
5. • Pregnant or breastfeeding woman
6. • Weight <40 Kg or > 100 Kg
7. • Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C. History of chronic alcohol abuse (consumption > 20 g/day
8. • Severe chronic heart failure or severe systolic dysfunction
9. • Recent (< 3 months) or incoming surgery requiring a general anaesthesia
10. • History of stem cell or organ transplantation (except corneas if performed more than 3 months prior inclusion)
11. • Hypersensitivity to bosentan or one of its excipients
12. • Prior treatment with any of the following: o Tocilizumab or methotrexate or secukinumab within 12 weeks preceding inclusion o Cell-depleting agents (i.e., anti-CD20) o Alkylating agents including cyclophosphamide o Hydroxychloroquine, cyclosporine A, dapsone, azathioprine, mycophenolate mofetil or janus kinase inhibitors within 4 weeks preceding inclusion o Tumor necrosis factor inhibitors within 8 weeks preceding inclusion o Anakinra within 1 week preceding inclusion
13. • Ongoing treatment with glibenclamide, fluconazole and rifampicin. Concomitant administration of both a CYP3A4 inhibitor or a CYP2C9 inhibitor
14. • Long-course systemic glucocorticoid therapy for other conditions than GCA or PMR
15. • Laboratory abnormalities: AST or ALT >3 x upper limit of normal (ULN)
16. • Infections: o Active hepatitis B or C o HIV infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Failure free survival at W52. A failure is defined by the occurrence of a relapse or the impossibility to decrease GC according to the predefined scheduled GC scheme.

Secondary endpoints 9

1. 1) Proportion of new ischemic event at W 52
2. 2) Proportion of patients in remission without prednisone at W52
3. 3) Proportion of patients in remission with prednisone ≤5 mg/day at W52
4. 4) Cumulative dose of prednisone at W52
5. 5) Quality of life measured by HAQ and SF36 at W 26 and W52
6. 6) Proportion of patient in remission at year 2
7. Secondary objectives and endpoints • SECONDARY objectives • EFFICACY: 1) To compare the occurrence of new ischemic event 2) To compare (bosentan versus reference group) the proportion of patients in remission without prednisone at W52 3) To compare (bosentan versus reference group) the proportion of patients in remission with ≤5 mg/day of prednisone at W52 4) To assess the GC-sparing effect of bosentan in the treatment of GCA 5) To assess the effect of bosentan on quality of life 6) To compare
8. 8) Proportion of patients receiving GC at year 2
9. 1) Frequency and type of side effects within 1 year after inclusion

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Alexis RÉGENT

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Alexis RÉGENT

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications