Clinical trial NCT06390436: Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis
Official title: Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis: an Open-label, Non-inferiority, Randomised Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Uveitis
Chronic Disease
Keywords: Adalimumab
Uveitis
Therapeutic drug monitoring
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
First posted: 2024-04-30
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SMOOTH is a multicenter, randomized, controlled, parallel-group, blinded end-point trial (Prospective Randomised Open, Blinded End-point, PROBE) designed to demonstrate the superiority of a TDM-based strategy of therapeutic de-escalation via the spacing of ADA administrations versus a conventional ADA-based therapeutic strategy.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maintenance of a complete ophthalmological response at 48 weeks
timeFrame: Week 48
measure: Infection
timeFrame: Week 48
Secondary outcomes:
measure: Maintenance of a complete ophthalmological response at 12 weeks
timeFrame: Weeks 12
measure: Maintenance of a complete ophthalmological response at 24 weeks
timeFrame: Weeks 24
measure: Maintenance of a complete ophthalmological response at 36 weeks
timeFrame: Weeks 36
measure: Infection
timeFrame: Week 12
measure: Infection
timeFrame: Week 24
measure: Infection
timeFrame: Week 36
measure: Anti-ADA antibody positivity
timeFrame: Weeks 12
measure: Anti-ADA antibody positivity
timeFrame: Weeks 24
measure: Anti-ADA antibody positivity
timeFrame: Weeks 36
measure: Anti-ADA antibody positivity
timeFrame: Weeks 48
Other outcomes:
Locations:
city: Avignon
country: France
facility: CH Avignon
city: Clermont-Ferrand
country: France
facility: Chu Montpied
city: Grenoble
country: France
facility: CHU Grenoble Alpes
city: Le Puy-en-Velay
country: France
facility: CH Le Puy-en-Velay
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Lyon
country: France
facility: HCL - Hôpital Edouard Herriot
city: Montpellier
country: France
facility: CHU MONTPELLIER - Hôpital Saint-Eloi
city: Paris
country: France
facility: APHP - Centre hospitalier national des Quinze-Vingts
city: Paris
country: France
facility: APHP - Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: APHP - Hôpital Cochin
city: Saint-Étienne
country: France
facility: Chu de Saint-Etienne
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Lucile GRANGE, MD
role: PRINCIPAL_INVESTIGATOR
References: