Clinical trial NCT03871361: Abatacept in Patients With Birdshot HLA A29 Uveitis
Official title: Abatacept in Patients With Birdshot HLA A29 Uveitis: A Phase II Prospective 0pen Label Interventional Proof-of-Concept Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Eye Diseases
Uveitis
Keywords: Birdshot Uveitis
HLA A29
Abatacept
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Netwerk Antwerpen (ZNA)
First posted: 2019-03-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective 0pen Label Interventional Proof-of-Concept Study
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of Abatacept as an immunosuppressive treatment in Birdshot uveitis. The primary objective is to test the efficacy to suppress inflammation in active Birdshot uveitis patients, using quantitative and qualitative measurements of visual function.

Detailed description: To assess the efficacy and safety of Abatacept as an immunosuppressive treatment in Birdshot uveitis. The primary objective is to assess the efficacy to suppress active uveitis in Birdshot uveitis and to induce inflammatory remission during the 1 year treatment and after 2 years of treatment. Treatment efficacy will be assessed, using quantitative and qualitative measurements of visual function. In this trial we will also assess the utility of quantitative outcome measures in detecting disease activity.

Eligibility criteria: Inclusion Criteria:

1. Subject is at least 18 years of age.
2. Subject is diagnosed with Birdshot uveitis, HLA A 29+
3. Subject must have active disease at the Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye :

   -Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesions

   -≥ 1+ vitreous haze (National Eye Institute \[NEI\]/SUN criteria)
4. Subjects who do not have previous, active or latent tuberculosis (TB). Subjects with negative QuantiFERON®-TB Gold test (or interferon-gamma release assay (IGRA) equivalent) are eligible. Subjects with a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA equivalent) result are not eligible. The TB screening tests are diagnostic tests. In the event of a negative TB screening test, the results are to be interpreted in the context of the patient's epidemiology, history, exam findings, etc. and it is the responsibility of the investigator to determine if a patient has previous, active or latent tuberculosis or not. Under no circumstances can a patient with a positive QuantiFERON®-TB Gold test (or IGRA equivalent) enter the study.

Exclusion Criteria:

1. Subject with prior inadequate response to high-dose oral corticosteroids (\>30 mg of prednisolone or equivalent)
2. Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV).
3. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial.
4. Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury.
5. Subject with Best Corrected Visual Acuity (BCVA) less than 20 letters (Early Treatment Diabetic Retinopathy Study) in at least one eye at the Baseline Visit.
6. Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis (e.g.presence or history of snowbanking or snowballs) and symptoms and/or magnetic resonance imaging (MRI) findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis or panuveitis that have signs of intermediate uveitis (e.g., presence or history of snowbanking or snowballs) must have had a brain MRI within 90 days prior to the Baseline Visit.
7. Subject has had previous exposure to anti-tumor necrosis factor (TNF) therapy or any biologic therapy (except intravitreal anti-vascular endothelial growth factor \[VEGF\] therapy) with a potential therapeutic impact on non-infectious uveitis
8. Subject with exposure to classic immunosuppressive therapy, in which the dose has been increased within the last 28 days prior to Baseline visit or is within the following doses at the screening visit: Methotrexate (MTX) \>25 mg per week Cyclosporine \> 4 mg/kg per day Mycophenolate mofetil \>2 grams per day or an equivalent drug to mycophenolate mofetil (e.g. mycophenolic acid) at an equivalent dose approved by the Medical Monitor. Azathioprine \> 175 mg per day Tacrolimus (oral formulation) \>8 mg per day.
9. Subject is still on immunosuppressive therapy ( Corticosteroids, Methotrexate, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Tacrolimus, Sirolimus) at the baseline visit.
10. Subject has received Iluvien® (glucocorticosteroids implant) within 3 years prior to the Baseline visit or that has had complications related to the device. Subject has had Iluvien® (glucocorticosteroids implant) removed within 90 days prior to the Baseline visit or has had complications related to the removal of the device.
11. Subject has received intraocular or periocular corticosteroids within 30 days prior to Baseline visit.
12. Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy. Subject with neovascular/wet age-related macular degeneration Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process. Subject with severe vitreous haze that precludes visualization of the fundus at the Baseline visit.
13. Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline visit. Subject has received intravitreal anti-VEGF therapy within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin® (bevacizumab) or within 60 days of the Baseline visit for anti-VEGF Trap (aflibercept).
14. Subject has received intravitreal methotrexate within 90 days prior to the Baseline visit
15. Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit.
16. Subject with macular edema as the only sign of uveitis.
17. Subject with a history of scleritis.
18. Subject on cyclophosphamide within 30 days prior to the Baseline visit.
19. Subjects with a known HIV, HepB/C infection.
20. Subjects with an active or recent acute infection.
21. Subjects with a history of chronic or recurrent bacterial, viral or systemic fungal infections.
22. Subjects with malignancies.
23. Subjects who have received any live vaccines within 3 months of the start of the study drug.

Primary outcomes:
measure: time to recurrence in ≥1 eye
timeFrame: 1 year and 2 years
Secondary outcomes:
measure: Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit
timeFrame: 1 year and 2 years
measure: Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit
timeFrame: 1 year and 2 years
measure: Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Baseline
timeFrame: 1 year and 2 years
measure: Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit
timeFrame: 1 year and 2 years
measure: Percent Change in Choroidal Thickness in Each Eye From Best State Achieved Prior to week 6 to the Final/Early Termination Visit
timeFrame: 1 year and 2 years
measure: Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Baseline to the Final/Early Termination Visit
timeFrame: 1 year and 2 years
measure: Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved
timeFrame: 1 year and 2 years
measure: Change in Full Field ElectroRetinoGraphy (ERG) using the ISCEV standard protocols from baseline until the Final Visit
timeFrame: 1 year and 2 years
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZLeuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Pieter-Paul FA Schauwvlieghe, MD
role: PRINCIPAL_INVESTIGATOR
References: