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Abatacept in Patients With Birdshot HLA A29 Uveitis (HLA-A29)

Primary Purpose

Eye Diseases, Uveitis

Status
Active
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Abatacept 125 MG/ML Prefilled Syringe
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Eye Diseases focused on measuring Birdshot Uveitis, HLA A29, Abatacept

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UZLeuven

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abatacept 125 MG/ML Prefilled Syringe

Arm Description

Participants will inject the drug at home on a weekly basis. Participants will receive the syringes on the visit dates, supplying them for the period until the next visit. At baseline, participants will be explained and shown how to inject the drug themselves. Subject will have to stop all concomitant immunosuppressive drugs at baseline, e.g. Corticosteroids, Methotrexate, Mofetil Mycophenolate, Azathioprine, Tacrolimus, Sirolimus or Cyclosporin. Other drugs can be continued. In case of recurrence in the abatacept group, the study will end for that subject. Patients treated with abatacept (ORENCIA) may receive concurrent vaccinations, except for live vaccines. Live vaccines should not be given concurrently with abatacept or within 3 months of its discontinuation.

Outcomes

Primary Outcome Measures

time to recurrence in ≥1 eye
Patients are assessed for recurrence, if at least 1 of the following criteria are fulfilled in at least 1 eye. worsening of BCVA (Best Corrected Visual Acuity measured by ETDRS chart) by >15 letters relative to baseline 30% increase of central retinal thickness on OCT (Optical Coherence Tomography) relative to baseline 2-step increase in VH (Vitreous Haze) grade relative to baseline new active, inflammatory choroidal (detected on ICG Angiography) and/or inflammatory retinal vascular lesions relative to baseline (detected on FA: fluorescein angiography).

Secondary Outcome Measures

Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit
Vitreous haze is measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.
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
Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Baseline
Optical coherence tomography is performed at every visit using the Zeiss Cirrus OCT. Images are evaluated by a central reader (PI). Macular edema is defined as cystoid macular edema. OCT evidence of macular edema on or after Baseline is to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema are to be considered as censored observations at the time of dropping out. Optical Coherence Tomography will be measured using the Zeiss Cirrus OCT. For each eye a macular cube slab 512x128 and 2 HD 5 lines rasters (1 on 180° and 1 on 90°) will be taken, centered on the fovea.
Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit
Optical coherence tomography is performed at every visit using the Zeiss Cirrus OCT.Retinal thickness will be measured on the macular cube slab centered on the fovea. This will be measured by a central reader (PI).
Percent Change in Choroidal Thickness in Each Eye From Best State Achieved Prior to week 6 to the Final/Early Termination Visit
Choroidal thickness will be measured using the EDI mode of the Zeiss Cirrus OCT (HD 5 lines raster) and will be measured by a central reader (PI).
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Baseline to the Final/Early Termination Visit
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning
Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved
Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved, as defined by the Angiography Scoring for Uveitis Working group using the Heidelberg Scanning LASER fluorescein and ICG angiography
Change in Full Field ElectroRetinoGraphy (ERG) using the ISCEV standard protocols from baseline until the Final Visit
Quantitative values, such as 30 Hz implicit time, amplitude in a and b wave and latency will be recorded

Full Information

First Posted
March 5, 2019
Last Updated
January 26, 2023
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Ziekenhuis Netwerk Antwerpen (ZNA)
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1. Study Identification

Unique Protocol Identification Number
NCT03871361
Brief Title
Abatacept in Patients With Birdshot HLA A29 Uveitis
Acronym
HLA-A29
Official Title
Abatacept in Patients With Birdshot HLA A29 Uveitis: A Phase II Prospective 0pen Label Interventional Proof-of-Concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 1, 2019 (Actual)
Primary Completion Date
January 1, 2022 (Actual)
Study Completion Date
January 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
Ziekenhuis Netwerk Antwerpen (ZNA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eye Diseases, Uveitis
Keywords
Birdshot Uveitis, HLA A29, Abatacept

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Prospective 0pen Label Interventional Proof-of-Concept Study
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Abatacept 125 MG/ML Prefilled Syringe
Arm Type
Experimental
Arm Description
Participants will inject the drug at home on a weekly basis. Participants will receive the syringes on the visit dates, supplying them for the period until the next visit. At baseline, participants will be explained and shown how to inject the drug themselves. Subject will have to stop all concomitant immunosuppressive drugs at baseline, e.g. Corticosteroids, Methotrexate, Mofetil Mycophenolate, Azathioprine, Tacrolimus, Sirolimus or Cyclosporin. Other drugs can be continued. In case of recurrence in the abatacept group, the study will end for that subject. Patients treated with abatacept (ORENCIA) may receive concurrent vaccinations, except for live vaccines. Live vaccines should not be given concurrently with abatacept or within 3 months of its discontinuation.
Intervention Type
Drug
Intervention Name(s)
Abatacept 125 MG/ML Prefilled Syringe
Other Intervention Name(s)
Orencia
Intervention Description
Abatacept 125 MG/ML Prefilled Syringe [Orencia] weekly
Primary Outcome Measure Information:
Title
time to recurrence in ≥1 eye
Description
Patients are assessed for recurrence, if at least 1 of the following criteria are fulfilled in at least 1 eye. worsening of BCVA (Best Corrected Visual Acuity measured by ETDRS chart) by >15 letters relative to baseline 30% increase of central retinal thickness on OCT (Optical Coherence Tomography) relative to baseline 2-step increase in VH (Vitreous Haze) grade relative to baseline new active, inflammatory choroidal (detected on ICG Angiography) and/or inflammatory retinal vascular lesions relative to baseline (detected on FA: fluorescein angiography).
Time Frame
1 year and 2 years
Secondary Outcome Measure Information:
Title
Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit
Description
Vitreous haze is measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.
Time Frame
1 year and 2 years
Title
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
Description
Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity is measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.
Time Frame
1 year and 2 years
Title
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Baseline
Description
Optical coherence tomography is performed at every visit using the Zeiss Cirrus OCT. Images are evaluated by a central reader (PI). Macular edema is defined as cystoid macular edema. OCT evidence of macular edema on or after Baseline is to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema are to be considered as censored observations at the time of dropping out. Optical Coherence Tomography will be measured using the Zeiss Cirrus OCT. For each eye a macular cube slab 512x128 and 2 HD 5 lines rasters (1 on 180° and 1 on 90°) will be taken, centered on the fovea.
Time Frame
1 year and 2 years
Title
Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit
Description
Optical coherence tomography is performed at every visit using the Zeiss Cirrus OCT.Retinal thickness will be measured on the macular cube slab centered on the fovea. This will be measured by a central reader (PI).
Time Frame
1 year and 2 years
Title
Percent Change in Choroidal Thickness in Each Eye From Best State Achieved Prior to week 6 to the Final/Early Termination Visit
Description
Choroidal thickness will be measured using the EDI mode of the Zeiss Cirrus OCT (HD 5 lines raster) and will be measured by a central reader (PI).
Time Frame
1 year and 2 years
Title
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Baseline to the Final/Early Termination Visit
Description
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning
Time Frame
1 year and 2 years
Title
Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved
Description
Change in scoring of Dual Fluorescein and ICG (Indocyanine Green) angiography from best state achieved, as defined by the Angiography Scoring for Uveitis Working group using the Heidelberg Scanning LASER fluorescein and ICG angiography
Time Frame
1 year and 2 years
Title
Change in Full Field ElectroRetinoGraphy (ERG) using the ISCEV standard protocols from baseline until the Final Visit
Description
Quantitative values, such as 30 Hz implicit time, amplitude in a and b wave and latency will be recorded
Time Frame
1 year and 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject is at least 18 years of age. Subject is diagnosed with Birdshot uveitis, HLA A 29+ 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) 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: Subject with prior inadequate response to high-dose oral corticosteroids (>30 mg of prednisolone or equivalent) 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). Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial. Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or evidence of glaucomatous optic nerve injury. 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. 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. 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 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. Subject is still on immunosuppressive therapy ( Corticosteroids, Methotrexate, Cyclosporine, Mycophenolate Mofetil, Azathioprine, Tacrolimus, Sirolimus) at the baseline visit. 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. Subject has received intraocular or periocular corticosteroids within 30 days prior to Baseline visit. 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. 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). Subject has received intravitreal methotrexate within 90 days prior to the Baseline visit Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit. Subject with macular edema as the only sign of uveitis. Subject with a history of scleritis. Subject on cyclophosphamide within 30 days prior to the Baseline visit. Subjects with a known HIV, HepB/C infection. Subjects with an active or recent acute infection. Subjects with a history of chronic or recurrent bacterial, viral or systemic fungal infections. Subjects with malignancies. Subjects who have received any live vaccines within 3 months of the start of the study drug.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pieter-Paul FA Schauwvlieghe, MD
Organizational Affiliation
Universitaire Ziekenhuizen KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZLeuven
City
Leuven
State/Province
Vlaams-Brabant
ZIP/Postal Code
3000
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.gegevensbeschermingsautoriteit.be
Description
Belgian Dataprotection Authority

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Abatacept in Patients With Birdshot HLA A29 Uveitis

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