UveitisPhase 4SMOOTHNCT06390436
Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis
A Phase 4 study testing Blood sample and Adalimumab Injection in people with Uveitis and Chronic Disease, run by Centre Hospitalier Universitaire de Saint Etienne at 11 sites in France.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveitis, Chronic Disease
- What is being tested?
- Blood sample and Adalimumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 11 sitesFrance
- Study dates
- Dec 2026to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
France11 sites
CH Avignon
Avignon, 84000
Chu Montpied
Clermont-Ferrand, 63003
CHU Grenoble Alpes
Grenoble, 38700
CH Le Puy-en-Velay
Le Puy-en-Velay, 43000
Hôpital de la Croix Rousse
Lyon, 69317
HCL - Hôpital Edouard Herriot
Lyon
CHU MONTPELLIER - Hôpital Saint-Eloi
Montpellier, 34090
APHP - Centre hospitalier national des Quinze-Vingts
Paris, 75012
APHP - Hôpital Pitié-Salpétrière
Paris, 75013
APHP - Hôpital Cochin
Paris, 75014
Chu de Saint-Etienne
Saint-Etienne, 42055
Lucile GRANGE, MD, (0)477828245 ext. +33, lucile.grange@chu-st-etienne.fr
Martin KILLIAN, MD, (0)477829179 ext. +33, martin.killian@chu-st-etienne.fr
About this study
Official title: Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis: an Open-label, Non-inferiority, Randomised Clinical Trial
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.
Read the 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.
- Conditions
- Uveitis, Chronic Disease
- Being tested
- Blood sample, Adalimumab Injection
- Keywords
- Adalimumab, Uveitis, Therapeutic drug monitoring
- Medical subject headings
- Uveitis, Chronic Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleDiagnostic 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.
Adalimumab InjectionDrug
Adalimumab Injection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Blood sample; Drug: Adalimumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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+.
Measured: 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.
Measured: Week 48
Secondary outcomes (10)
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+.
Measured: Weeks 12
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+.
Measured: Weeks 24
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+.
Measured: Weeks 36
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.
Measured: Week 12
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.
Measured: Week 24
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.
Measured: Week 36
Anti-ADA antibody positivity
Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL
Measured: Weeks 12
Anti-ADA antibody positivity
Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL
Measured: Weeks 24
Anti-ADA antibody positivity
Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL
Measured: Weeks 36
Anti-ADA antibody positivity
Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL
Measured: Weeks 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2024
- Study startDec 2026 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for UveitisStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de Saint EtienneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Direction Générale de l'Offre de Soins
- Responsible party
- Sponsor
- Investigators
- Lucile GRANGE, MD, Principal investigator, Centre Hospitalier Universitaire de Saint Etienne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06390436
- Sponsor's protocol ID
- 23PH187
- Other IDs
- 2023-509733-39-00, 2023
- Acronym
- SMOOTH
- Status last verified
- Jul 2026
- First submitted
- 25 Apr 2024
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis: an Open-label, Non-inferiority, Randomised Clinical Trial
- ClinicalTrials.gov ID
- NCT06390436
- Acronym / sponsor ID
- SMOOTH / 23PH187
- Conditions
- Uveitis, Chronic Disease
- Keywords
- Adalimumab, Uveitis, Therapeutic drug monitoring
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de Saint EtienneUniversity, hospital or other
- Collaborators
- Direction Générale de l'Offre de Soins
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 30 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Control arm : conventional strategy | Active comparator | Diagnostic Test: Blood sample, Drug: Adalimumab InjectionAt 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. |
| Arm 2: Interventional arm : adalimumab dose spacing strategy | Experimental | Diagnostic Test: Blood sample, Drug: Adalimumab InjectionAt 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood sampleA 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. | Diagnostic test | Arm 2: Interventional arm : adalimumab dose spacing strategy, Control arm : conventional strategy |
| Adalimumab InjectionAdalimumab Injection | Drug | Arm 2: Interventional arm : adalimumab dose spacing strategy, Control arm : conventional strategy |
Primary outcome
Maintenance of a complete ophthalmological response at 48 weeks
Time frame: Week 48
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+.
Infection
Time frame: Week 48
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.
10 secondary outcomes
Maintenance of a complete ophthalmological response at 12 weeks
Time frame: Weeks 12
Maintenance of a complete ophthalmological response at 24 weeks
Time frame: Weeks 24
Maintenance of a complete ophthalmological response at 36 weeks
Time frame: Weeks 36
Infection
Time frame: Week 12
Infection
Time frame: Week 24
Infection
Time frame: Week 36
Anti-ADA antibody positivity
Time frame: Weeks 12
Anti-ADA antibody positivity
Time frame: Weeks 24
Anti-ADA antibody positivity
Time frame: Weeks 36
Anti-ADA antibody positivity
Time frame: Weeks 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lucile GRANGE, MD principal investigator
Centre Hospitalier Universitaire de Saint Etienne
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Blood sample and Adalimumab Injection in people with Uveitis and Chronic Disease, run by Centre Hospitalier Universitaire de Saint Etienne at 11 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lucile GRANGE, MD ((0)477828245 ext. +33, lucile.grange@chu-st-etienne.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maintenance of a complete ophthalmological response at 48 weeks (time frame: Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.