A Trial of the Efficacy and Safety of Izokibep in the Treatment of Non-anterior Uveitis

Not Recruiting

Trial ID: NCT04706741


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).

Official Title

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)

Stanford Investigator(s)

Quan Dong Nguyen, MD, MSc
Quan Dong Nguyen, MD, MSc

Professor of Ophthalmology and, by courtesy, of Pediatrics and of Medicine (Immunology & Rheumatology)


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), Fundus Photography, Fluorescein
      angiography (FA), spectral-domain optical coherence tomography (SD-OCT) to
      determine whether a lesion is active or inactive (the central reader's assessment
      using FA, FP, and or SD-OCT 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

   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

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


drug: Prednisone/Prednisolone

drug: Izokibep

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305