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

NCT06390436 | Not Yet Recruiting Phase 4

• 2 other identifiers: 23PH1872023-509733-39-00
• Study Type: interventional
• Target: 320
• Locations: 1 country
• Sites: 11

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.

Conditions

Uveitis; Chronic Disease

Keywords

Adalimumab; Uveitis; Therapeutic drug monitoring

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Maintenance of a complete ophthalmological response at 12 weeks

  Weeks 12

• Maintenance of a complete ophthalmological response at 24 weeks

  Weeks 24

• Maintenance of a complete ophthalmological response at 36 weeks

  Weeks 36

• Infection

  Week 12

• Infection

  Week 24

Study Arms (2)

Control arm : conventional strategy

ACTIVE COMPARATOR

At W0, ADA administration will be continued every 14 days. At W24, the control arm will continue to receive ADA every 14 days regardless of serum ADA concentration.

Diagnostic Test: Blood sample; Drug: Adalimumab Injection

Arm 2: Interventional arm : adalimumab dose spacing strategy

EXPERIMENTAL

At W0, if the serum ADA concentration is ≥ 8 μg/mL, ADA administration will be spaced every 21 days. At W24, if the ADA concentration is \< 3.3 μg/mL (having a serum ADA concentration above this threshold was associated with a complete therapeutic response according to one study), administrations will be repeated every 14 days. If the ADA concentration is ≥ 3.3 and \< 8μg/mL, administrations will be left every 21 days. If ADA concentration is still ≥8μg/mL, ADA administrations will be spaced every 28 days.

Diagnostic Test: Blood sample; Drug: Adalimumab Injection

Interventions

Blood sample DIAGNOSTIC_TEST

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.

Arm 2: Interventional arm : adalimumab dose spacing strategy; Control arm : conventional strategy

Adalimumab Injection DRUG

Adalimumab Injection

Arm 2: Interventional arm : adalimumab dose spacing strategy; Control arm : conventional strategy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Direction Générale de l'Offre de Soins: collaborator

Study Sites (11)

CH Avignon

Avignon, 84000, France

Location

Chu Montpied

Clermont-Ferrand, 63003, France

Location

CHU Grenoble Alpes

Grenoble, 38700, France

Location

CH Le Puy-en-Velay

Le Puy-en-Velay, 43000, France

Location

Hôpital de la Croix Rousse

Lyon, 69317, France

Location

HCL - Hôpital Edouard Herriot

Lyon, France

Location

CHU MONTPELLIER - Hôpital Saint-Eloi

Montpellier, 34090, France

Location

APHP - Centre hospitalier national des Quinze-Vingts

Paris, 75012, France

Location

APHP - Hôpital Pitié-Salpétrière

Paris, 75013, France

Location

APHP - Hôpital Cochin

Paris, 75014, France

Location

Chu de Saint-Etienne

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

Uveitis; Chronic Disease

Interventions

Blood Specimen Collection; Adalimumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lucile GRANGE, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucile GRANGE, MD

CONTACT

(0)477828245; lucile.grange@chu-st-etienne.fr

Martin KILLIAN, MD

CONTACT

(0)477829179; martin.killian@chu-st-etienne.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The primary endpoint will be assessed by blinding the allocated treatment group to investigator. Thus, ophthalmological response will be assessed in a standardised manner by an ophthalmologist, blinded to the treatment strategy. The occurrence of infections will also be assessed in a manner blinded to the by an independent adjudication committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)