Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis

Chronic Disease Clinical Trial

— SMOOTH  

Official title:

Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis: an Open-label, Non-inferiority, Randomised Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390436
• Other study ID #: 23PH187
• Secondary ID: 2023-509733-39-0
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 2025
• Est. completion date: January 2029

Study information

• Verified date: April 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: Lucile GRANGE, MD
• Phone: (0)477828245
• Email: lucile.grange[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Uveitis and its complications are thought to account for 10 to 15% of preventable blindness in Western countries. The diagnosis of chronic non-infectious uveitis (CNUI) can be made after exclusion of pseudo uveitis or infectious uveitis, in the case of any persistent uveitis or uveitis with frequent relapses occurring less than 3 months after cessation of treatment. Adalimumab (ADA), an anti-TNFα monoclonal antibody, has marketing authorization and is widely used in the treatment of UCNI as a relay to corticosteroids. The use of ADA has been optimized, in particular through Therapeutic Drug Monitoring (TDM), based on the determination of serum ADA levels and anti-ADA antibodies. Recently, an article showed that a strategy of spacing ADA administrations in RA patients with concentrations >8 μg/mL was not inferior to standard.

Description:

There is currently no formal recommendation for spacing ADA administration in patients with chronic noninfectious uveitis, but promising data from a recent retrospective study conducted by the Croix-Rousse team, led to the proposal of a decision support algorithm. Following the example of what has been shown in rheumatoid arthritis, the investigators propose to compare a strategy of spacing ADA administrations in patients with a satisfactory clinical response associated with high serum ADA concentrations.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 320
• Est. completion date: January 2029
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed and having signed the study consent form
• Age = 18 years
• NICU according to the Standardization of Uveitis Nomenclature (SUN) criteria
• Complete ophthalmological response for = 48 weeks (96 weeks for uveitis related to Behçet's disease), all treatments combined
• On ADA 40mg / 14 days for = 24 weeks (i.e. achievement of the steady state for ADA concentrations)
• Not having received systemic corticosteroid therapy for = 12 weeks

Exclusion Criteria:

• Inability or refusal to understand and/or sign the informed consent form to participate in the study.
• Inability and/or refusal to carry out the follow-up examinations required for the study.
• Modification of any background immunomodulatory treatment (e.g. methotrexate, hydroxychloroquine, mycophenolate, etc.) associated with ADA, during the 12 weeks prior to inclusion.
• Uveitis suspected or proven to be of infectious origin
• Planned surgery (or other foreseeable medical event) requiring discontinuation of ADA for the duration of the study.

Related Conditions & MeSH terms

• Chronic Disease
• Uveitis

Intervention

Diagnostic Test:
• Blood sample
A blood sample will be taken, in addition to blood samples taken for the usual follow-up, with 4 dry tubes for the determination of ADA and anti-ADA antibodies and for bio-collection.

Drug:
• Adalimumab Injection
Adalimumab Injection

Locations

Country	Name	City	State
France	CH Avignon	Avignon
France	Chu Montpied	Clermont-Ferrand
France	CHU Grenoble Alpes	Grenoble
France	CH Le Puy-en-Velay	Le Puy-en-Velay
France	HCL - Hôpital Edouard Herriot	Lyon
France	Hôpital de la Croix Rousse	Lyon
France	CHU MONTPELLIER - Hôpital Saint-Eloi	Montpellier
France	APHP - Centre hospitalier national des Quinze-Vingts	Paris
France	APHP - Hôpital Cochin	Paris
France	APHP - Hôpital Pitié-Salpétrière	Paris
France	Chu de Saint-Etienne	Saint-Étienne

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Direction Générale de l'Offre de Soins

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maintenance of a complete ophthalmological response at 48 weeks	Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous = 0.5+.	Week 48
Primary	Infection	Number of infection during follow-up for up to 48 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever =38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee.	Week 48
Secondary	Maintenance of a complete ophthalmological response at 12 weeks	Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous = 0.5+.	Weeks 12
Secondary	Maintenance of a complete ophthalmological response at 24 weeks	Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous = 0.5+.	Weeks 24
Secondary	Maintenance of a complete ophthalmological response at 36 weeks	Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous = 0.5+.	Weeks 36
Secondary	Infection	Number of infection during follow-up for up to 12 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever =38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee.	Week 12
Secondary	Infection	Number of infection during follow-up for up to 24 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever =38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee.	Week 24
Secondary	Infection	Number of infection during follow-up for up to 36 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever =38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee.	Week 36
Secondary	Anti-ADA antibody positivity	Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in µg/mL	Weeks 12
Secondary	Anti-ADA antibody positivity	Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in µg/mL	Weeks 24
Secondary	Anti-ADA antibody positivity	Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in µg/mL	Weeks 36
Secondary	Anti-ADA antibody positivity	Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in µg/mL	Weeks 48