Study of the Intravitreal Plasma Kallikrein Inhibitor, KVD001, in Subjects With Center-involving Diabetic Macular Edema (ciDME)
Condition: Diabetic Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: KVD001 Injection; Sham Procedure
Intervention description: Intravitreal KVD001 Injection; Sham Procedure
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a clinical study where patients with diabetes and a vision threatening eye condition
      called "Diabetic Macular Edema" receive four injections into the eye at monthly intervals.
      The patients will already have tried the standard of care without complete success. The
      patients will be randomized to receive either a high dose, a low dose or a sham control
      treatment. The study will evaluate whether the new treatment improves vision and whether it
      changes the underlying course of the disease in the eye.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of Type I or Type II diabetes mellitus (DM).

          -  BCVA of ≥19 letters (~20/400) and ≤73 letters (~20/40) in the study eye and ≥34
             letters(~20/200 or better) in the fellow eye.

          -  Presence of ciDME in the study eye defined as CST ≥305 μm in women and ≥320 μm in men

          -  Subjects first anti-VEGF injection in the study eye occurred ≤36 months.

          -  Subjects have received at least 3 anti-vascular endothelial growth factor (VEGF)
             injections in the study eye within a 6-month period.

          -  The last anti-VEGF injection in the study eye is ≥ 8 weeks.

        Exclusion Criteria:

          -  Evidence of ocular pathology (e.g. visually significant cataract) that impacts
             subject's vision in the study eye from any cause other than DME.

          -  Evidence/presence of amblyopia, vitreomacular traction, epiretinal membrane, foveal
             atrophy, or foveal ischemia, or any other condition in the macula that is thought to
             impair the subject's vision (other than DME).

          -  Prior treatment with panretinal photocoagulation or focal grid macular
             photocoagulation in the study eye within the previous 3 months.

          -  Prior treatment with intravitreal (IVT) steroid in the study eye (in the previous 3
             months for triamcinolone, previous 6 months for Ozurdex and at any time for Iluvien).

          -  Prior treatment with topical NSAIDs or topical steroids in the study eye within 1
             month.

          -  Prior treatment with systemic corticosteroids or systemic anti-VEGF therapy within 3
             months.

          -  Prior vitrectomy in the study eye.

          -  Prior intraocular surgery in the study eye except for cataract surgery. Cataract
             surgery within the previous 6 months in the study eye is excluded.

          -  Intraocular pressure (IOP) of >22 mmHg in the study eye or use of >2 antiglaucoma
             agents (combination agents count as 2 agents) in the study eye.

          -  Evidence of infectious dacrocystitis, significant blepharitis, active conjunctivitis,
             infectious keratitis, or scleritis in either eye, or any other condition that might
             affect the safety of the IVT injection.

          -  Current active proliferative diabetic retinopathy (PDR), active anterior segment
             neovascularization (ASNV), active retinal neovascularization, or the presence of
             vitreous hemorrhage in the study eye.

          -  Poorly controlled DM.

          -  Uncontrolled hypertension

          -  Prior treatment with ocriplasminin the study eye within 3 months