Evaluation of K9 in Subjects with Diabetic Macular Edema (DME)

A non-randomized study evaluating the safety of an orally administered inflammasome inhibitor, K9, for the treatment of diabetic macular edema (DME).

This is an eight (8) week non-randomized, open-label, safety study evaluating twice daily, oral K9 in five (5) patients. Subjects with DME meeting inclusion/exclusion criteria will be offered enrollment into this study. A screening visit and subject selection criteria will be used to assess subject eligibility prior to enrollment. Patients will be supplied with tablets of K9 to be taken orally BID for 28 days (4 weeks). Safety will be assessed over a series of postoperative visits over an 8 week period.

Eligibility Criteria:
Inclusion Criteria:

* BCVA of ≥ 24 and ≤ 68 letters (20/50 or worse but at least 20/320) by an ETDRS chart. BCVA of the non-study eye must be no worse than 20/400 Snellen equivalent)
* Diagnosis of diabetes mellitus, type 1 or 2 with non-proliferative or non-high risk proliferative diabetic retinopathy. Any one of the following will be considered sufficient evidence that diabetes is present:
* Current regular use of insulin for the treatment of diabetes
* Current regular use of oral hypoglycemic agents for the treatment of diabetes
* DME based on investigator's clinical evaluation and demonstrated on fundus photographs, fluorescein angiograms, and/or spectral domain-optical coherence tomography (SD-OCT)
* Mean foveal thickness of at least 325 µm by SD-OCT
* Ability and willingness to comply with the treatment and follow up procedures
* Ability to understand and sign the informed consent form
* Intraocular pressure of ≤ 21 mm Hg on 2 or fewer IOP lowering medications

Exclusion Criteria:

* Pregnant patients, currently lactating patients, or females of childbearing potential (unless using reliable contraception such as double barrier, surgical sterilization, oral contraceptives, intrauterine device (IUD), etc.
* Body weight less than 55 kg
* Allergy or hypersensitivity (known or suspected) to fluorescein or any component of the investigational product or delivery system
* Any ocular surgery in the study eye within 12 weeks of screening
* History of vitrectomy in the study eye
* Aphakia in the study eye
* Presence of severe foveal ischemia, defined as foveal avascular zone (FAZ) of \>1.5 mm2 on OCT-Angiography
* Prior intraocular or periocular treatment for DME including any of the following:
* Intravitreous injection of anti-VEGF therapies including but not limited to bevacizumab, ranibizumab, aflibercept, faricimab, and/or brolucizumab within the last 3 months
* Intravitreous or sub-Tenon delivery of any steroid therapy (such as triamcinolone, dexamethasone) in the last 12 months or a fluocinolone acetonide implant for 3 years.
* Macular laser for the treatment of diabetic macular edema within 6 months of screening
* Any change in systemic steroidal therapy within 3 months of screening
* Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy (e.g. presumed ocular histoplasmosis, high myopia (spherical equivalent greater than 8 diopters), macular degeneration)
* History or presence of viral disease of the cornea or conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, any mycobacterial infections of the eye, or any fungal disease of any ocular structure or history of infectious retinitis
* History or presence of any disease or condition that in the investigator's opinion would preclude study treatment or follow-up or that in the opinion of the investigator would render them as unlikely to benefit from study treatment.
* History or presence of any other condition except for DME that could affect interpretation of study assessments (for example, but not limited to, geographic atrophy, macular hole, macular pucker, foveomacular traction, retinal vein occlusion, retinal degenerations)
* Any lens or corneal opacity which impairs visualization of the posterior pole
* Participation in another clinical trial within 12 weeks before the screening visit or during the study
* History of any clinically significant medical disorders the principal investigator considers exclusionary, including (but not limited to), neuromuscular, hematological disease, immune deficiency state, respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, neoplastic disease, renal or urinary tract diseases, or dermatological disease.
* History or current evidence of hypersensitivity to any components of the study medication, as assessed by the investigator.
* Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. Clinical trials solely involving observation, over-the-counter vitamins, supplements, or diets are not exclusionary.
* Expectation that subject will be moving away from the area of the clinical treatment center without the ability to return for visits within the study period