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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-509733-39-00 | Other Identifier | CTIS |
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| Name | Class |
|---|---|
| Direction Générale de l'Offre de Soins | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Lucile GRANGE, MD | Contact | (0)477828245 | +33 | lucile.grange@chu-st-etienne.fr |
| Martin KILLIAN, MD | Contact | (0)477829179 | +33 | martin.killian@chu-st-etienne.fr |
| Name | Affiliation | Role |
|---|---|---|
| Lucile GRANGE, MD | Centre Hospitalier Universitaire de Saint Etienne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CH Avignon | Avignon | 84000 | France | |||
| Chu Montpied |
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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.
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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.
| Adalimumab Injection | Drug | Adalimumab Injection |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Anti-ADA antibody positivity | Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL | Weeks 12 |
| Anti-ADA antibody positivity | Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL | Weeks 24 |
| Anti-ADA antibody positivity | Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL | Weeks 36 |
| Anti-ADA antibody positivity | Anti-ADA antibody positivity by a "drug sensible" test (i-Tracker anti-ADA) in μg/mL | Weeks 48 |
| Clermont-Ferrand |
| 63003 |
| France |
| CHU Grenoble Alpes | Grenoble | 38700 | France |
| CH Le Puy-en-Velay | Le Puy-en-Velay | 43000 | France |
| Hôpital de la Croix Rousse | Lyon | 69317 | France |
| HCL - Hôpital Edouard Herriot | Lyon | France |
| CHU MONTPELLIER - Hôpital Saint-Eloi | Montpellier | 34090 | France |
| APHP - Centre hospitalier national des Quinze-Vingts | Paris | 75012 | France |
| APHP - Hôpital Pitié-Salpétrière | Paris | 75013 | France |
| APHP - Hôpital Cochin | Paris | 75014 | France |
| Chu de Saint-Etienne | Saint-Etienne | 42055 | France |
|
| ID | Term |
|---|---|
| D014605 | Uveitis |
| D002908 | Chronic Disease |
| ID | Term |
|---|---|
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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