A Trial of the Efficacy and Safety Trial of ABY-035 in the Treatment and Prevention of Relapse/Recurrence of Non-anterior Uveitis

A Phase 2 Trial of the Efficacy and Safety of the Interleukin-17A Inhibitor ABY-035 in the Treatment and Prevention of Relapse/Recurrence of Non-infectious Intermediate, Posterior or Pan-uveitis, Including an Initial Pilot Phase

Sponsors

Lead Sponsor: Affibody

Source Affibody
Brief Summary

This is a multinational, multicenter, phase 2 proof-of-concept trial to explore the efficacy and safety of ABY-035 in treating and preventing relapse/recurrence of disease activity in patients with non-Infectious Intermediate, Posterior, Pan-Uveitis with significant BL disease activity despite treatment with stable doses of corticosteroids (≥7 to ≤40 mg/day oral prednisolon or equivalent).

Overall Status Not yet recruiting
Start Date April 2021
Completion Date December 2023
Primary Completion Date December 2023
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to Treatment Failure Week 10 to Week 50
Enrollment 110
Condition
Intervention

Intervention Type: Drug

Intervention Name: ABY-035

Description: ABY-035 is an Interleukin-17 Inhibitor that will be administered subcutaneously

Intervention Type: Drug

Intervention Name: Prednisolone/Prednisone

Description: Background Corticosteroid

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo to ABY-035

Arm Group Label: Placebo and corticosteroid burst

Eligibility

Criteria:

Inclusion Criteria: 1. ≥18 years of age at SCR 2. Previously documented medical history with diagnosed unilateral or bilateral NIIPPU 3. Active disease at BL defined by the presence of at least 1 of the following criteria in at least one eye despite treatment with stable doses of corticosteroids for at least 2 weeks: 1. Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion by Dilated Indirect Ophthalmoscopy (DIO) and Fundus Photography to determine whether a lesion is active or inactive (the central reader's assessment using Fundus Photography is required to confirm eligibility). 2. ≥2+ vitreous haze ( NEI/SUN criteria) by DIO and Fundus Photography (the central reader's assessment using Fundus Photography is required to confirm eligibility). 4. On treatment with oral corticosteroids (≥7 to ≤40 mg/day oral prednisolon or equivalent) at a stable dose for at least 2 weeks before BL Exclusion Criteria: 1. Subject with isolated anterior uveitis 2. Subject with Occlusive Behçet's disease, Acute Posterior Multifocal Placoid Pigment Epitheliopathy, Acute Posterior Pigment Epithelitis, Multiple Evanescent White Dot Syndrome, Punctate Inner Choroiditis or serpiginous choroidopathy 3. Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, syphilis, cytomegalovirus, Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 infection, Whipple's disease, herpes zoster virus, and herpes simplex virus 4. Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial 5. Planned (elective) eye surgery within 80 weeks after BL 6. History of prior refractive laser surgery, retinal laser photocoagulation, or neodymium-doped yttrium aluminium garnet posterior capsulotomy within 30 days before BL 7. History of any other prior ocular surgery within 90 days before BL 8. Subject with intraocular pressure (IOP) of ≥25 mmHg while on ≥2 glaucoma medications or evidence of glaucomatous optic nerve injury 9. Subject with severe vitreous haze that precludes visualization of the fundus at BL 10. Subject has a contraindication for mydriatic eye drops OR subject cannot be dilatated sufficiently well to permit good fundus visualization 11. Subject with BCVA <20 letters (ETDRS) in at least one eye at BL 12. Subject with intermediate uveitis or panuveitis who has presence or history of whitish exudates on the inferior pars plana (snowbanking) or vitreal inflammatory aggregates (snowballs) in combination with a medical history or signs or symptoms suggestive of a demyelinating disease such as multiple sclerosis 13. Subject with proliferative or severe non-proliferative diabetic retinopathy or clinically significant macular edema due to diabetic retinopathy 14. Subject with neovascular/wet age-related macular degeneration 15. Subject with an abnormality of the vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process 16. Subject with a history of active scleritis within 12 months of SCR Criteria that relate to comorbidity 17. Uncontrolled inflammatory bowel disease 18. Infection requiring treatment with IV anti-infectives within 30 days before BL or oral anti-infectives within 14 days before BL 19. Subject with any active infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the trial 20. History or any signs of lymphoproliferative disease, or a known malignancy or a history of malignancy within the previous 3 years (except for basal cell or squamous cell carcinoma of the skin that had been fully excised with no evidence of recurrence) Criteria that relate to laboratory testing 21. A positive test for subclinical/latent TB infection (i.e. positive QuantiFERON®-TB Gold test or equivalent product) suggestive of TB at SCR will require that the subject is thoroughly evaluated for active tuberculosis. If the subject is diagnosed with latent TB and active TB can be ruled out, the subject can be included if the subject has gone through an adequate course of prophylaxis as per local standard of care 12 weeks prior to SCR. 22. Positive Fluorescent treponemal (FTA)- absorption test (syphilis) 23. Subject with intolerance to high-dose oral corticosteroids (equivalent to oral prednisolon 1 mg/kg/day or 60 mg/day) 24. The subject has received any biologic therapy (including ABY-035 or any other IL-17i or IL-17 receptor inhibitor, e.g. secukinumab, ixekizumab, brodalumab or anti-TNF-alpha therapy) within 8 weeks before BL. 25. Subject on >1 concomitant non-biologic NCSIT 26. Subject on 1 concomitant non-biologic NCSIT: a) But the medication is not listed as permissible b) The medication is listed as permissible, but the dose has not been stable within the last 3 months before BL c) The medication is listed as permissible, but the dose exceeds the allowable level; to be acceptable, the dose needs to be: i) Methotrexate (MTX) ≤25 mg/week ii) CsA ≤4 mg/kg/day iii) Mycophenolate mofetil ≤2 grams/day or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid) at an equivalent dose approved by the Medical monitor iv) Azathioprine ≤175 mg/day v) Tacrolimus (oral formulation) ≤8 mg/day 28] The subject has received Retisert®, Iluvien®, or Yutiq® (glucocorticosteroids implant) within 3 years before BL or who has had complications related to the device. The subject has had any of these glucocorticosteroids implant (glucocorticosteroid implant) removed within 90 days before BL or has had complications related to the removal of the device 29] The subject has received intraocular or periocular corticosteroids within 90 days before BL 30] The subject has received Ozurdex® (dexamethasone implant) within 6 months before BL 31] The subject has received intravitreal methotrexate within 90 days before BL 32] The subject has received intravitreal anti- Vascular Endothelial Growth Factor (VEGF) therapy: 1. within 45 days of BL for Lucentis® (ranibizumab) or Avastin® (bevacizumab) 2. or within 60 days of BL for anti-VEGF Trap (aflibercept) 3. or within 84 days of BL for Beovu® (brolucizumab) 33] Subject on systemic carbonic anhydrase inhibitor within 1 week before SCR 34] Subject on cyclophosphamide within 30 days before BL 35] Prior or current use of chlorambucil

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Last Name: Karin Grünbaum

Phone: +46730718201

Email: [email protected]

Verification Date

December 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Label: ABY-035 and maintenance corticosteroid dose

Type: Experimental

Description: ABY-035 + Prednisolon/Prednisone

Label: ABY-035 and corticosteroid burst

Type: Experimental

Description: ABY-035 + Prednisolon/Prednisone

Label: Placebo and corticosteroid burst

Type: Placebo Comparator

Description: Placebo + Prednisolon/Prednisone

Acronym LINNAEA
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: The primary purpose of the study is prevention of relapse/recurrence of Noninfectious Intermediate, Posterior or Pan-uveitis The trial consist of two parts, a pilot part - Part A - and Part B Part A includes one treatment arm (Arm-0) Part B is planned to include 3 treatment arms - to which the subjects will be randomized

Primary Purpose: Treatment

Masking: None (Open Label)

Masking Description: Part A will be open-label. Part B (arm-2 and arm-3) will be masked with regards to ABY-035/Placebo

Source: ClinicalTrials.gov