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Jennifer K Sun, Raj K Maturi, David S Boyer, John A Wells, Victor H Gonzalez, Robert Tansley, Helen Hernandez, Lloyd P Aiello; Intravitreous Plasma Kallikrein (PK) Inhibition for Diabetic Macular Edema: A Phase 1 Study of the Novel PK Inhibitor KVD001. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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To assess local and systemic safety and pharmacokinetics of KVD001, a novel intravitreous plasma kallikrein inhibitor in patients with central involved diabetic macular edema (CIDME). In addition, to obtain exploratory pharmacodynamics data from eyes with visual loss from CIDME treated with KVD001.
A phase 1, open-label study was conducted, enrolling 1 study eye from each adult diabetic participant with CIDME [Spectralis OCT central subfield thickness ≥305 µm (women) and ≥320 µm (men)] and best corrected electronic ETDRS visual acuity (VA) score equivalent to Snellen VA 20/40-20/400. All study eyes had previously received anti-VEGF. Three cohorts of 3 participants each were given a single ascending dose of KVD001 with an additional 5 subjects dosed at the highest dose.
KVD001 was administered by intravitreous injection to 14 subjects (6 female; 13 with Type 2 diabetes (DM); mean age 60.9 yrs; DM duration 18.4 years; HbA1c 7.5%). No dose limiting toxicities or serious adverse events (SAE) were reported. One severe AE occurred: IOP elevation immediately after injection necessitating an aqueous paracentesis. Other ophthalmic AEs were consistent with known sequelae of intravitreous injection, such as subconjunctival hemorrhage (4), superficial punctate keratitis (4), and conjunctival injection (3). There were no reported drug-related systemic AEs. Study eye multifocal electroretinograms were comparable between baseline and Day 28 with no consistent changes in amplitude or response delay. Plasma KVD001 was detected at very low levels (peak <10pg/mL) at all doses up to 24 hours post-injection. Up to Day 56, no study eye required rescue medication and 12/14 participants followed up through Day 84 without additional treatment. Ten out of 14 study eyes had reduced central retinal thickness and 12/14 had VA that was improved at either Day 28 or 56 as compared with baseline.
KVD001 appeared safe and well tolerated with no drug-related ophthalmic or systemic safety issues through the highest dose administered. Systemic absorption was low. Although this was not an efficacy study, improvement of retinal edema and vision occurred to some extent in most study eyes. These results support evaluation of KVD001 in larger, controlled studies to further investigate its safety and efficacy in eyes with DME.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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