A Phase 2 Trial of the Efficacy and Safety of the Interleukin-17A Inhibitor Izokibep (ABY-035) in the Treatment of Non-infectious Intermediate, Posterior or Pan-uveitis (LINNAEA)
A Phase 2 Trial of the Efficacy and Safety of the Interleukin-17A Inhibitor Izokibep (ABY-035) in the Treatment of Non-infectious Intermediate, Posterior or Pan-uveitis (LINNAEA)
This is a multicenter, phase 2 trial to explore the efficacy and safety of Izokibep (ABY-035) in treating disease activity in patients with non-Infectious Intermediate, Posterior, Pan-Uveitis with significant disease activity at BL despite treatment with stable doses of corticosteroids (≥7 to ≤40 mg/day oral prednisolon or equivalent).
This is a multicenter, phase 2 trial to explore the efficacy and safety of Izokibep (ABY-035) in treating disease activity in patients with non-Infectious Intermediate, Posterior, Pan-Uveitis with significant disease activity at BL despite treatment with stable doses of corticosteroids (≥7 to ≤40 mg/day oral prednisolon or equivalent).
Inclusion Criteria:
≥18 years of age at SCR
Previously documented medical history with diagnosed unilateral or bilateral NIIPPU
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:
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:
Subject with isolated anterior uveitis
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
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
Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial
Planned (elective) eye surgery within 80 weeks after BL
History of prior refractive laser surgery, retinal laser photocoagulation, or neodymium-doped yttrium aluminium garnet posterior capsulotomy within 30 days before BL
History of any other prior ocular surgery within 90 days before BL
Subject with intraocular pressure (IOP) of ≥25 mmHg while on ≥2 glaucoma medications or evidence of glaucomatous optic nerve injury
Subject with severe vitreous haze that precludes visualization of the fundus at BL
Subject has a contraindication for mydriatic eye drops OR subject cannot be dilatated sufficiently well to permit good fundus visualization
Subject with BCVA <20 letters (ETDRS) in at least one eye at BL
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
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 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
Subject with a history of active scleritis within 12 months of SCR Criteria that relate to comorbidity
Uncontrolled inflammatory bowel disease
Infection requiring treatment with IV anti-infectives within 30 days before BL or oral anti-infectives within 14 days before BL
Subject with any active infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the trial
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
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.
Positive Fluorescent treponemal (FTA)- absorption test (syphilis)
Subject with intolerance to high-dose oral corticosteroids (equivalent to oral prednisolon 1 mg/kg/day or 60 mg/day)
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.
Subject on >1 concomitant non-biologic NCSIT
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: