Study of the Intravitreal Plasma Kallikrein Inhibitor, KVD001, in Subjects With Center-involving Diabetic Macular Edema (ciDME)

A Randomized Sham-controlled Double-masked Phase 2a Study of the Efficacy, Safety and Tolerability of the Intravitreal Plasma Kallikrein Inhibitor, KVD001, in Subjects With Center-involving Diabetic Macular Edema Who Have Had Prior Anti-vascular Endothelial Growth Factor Treatment

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Other: Sham Procedure; Drug: KVD001 Injection

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • KalVista Investigative Site
    • Phoenix, Arizona, United States, 85053
      • KalVista Investigative Site
    • Tucson, Arizona, United States, 85704
      • KalVista Investigative Site
  • California
    • Arcadia, California, United States, 91007
      • KalVista Investigative Site
    • Beverly Hills, California, United States, 90211
      • KalVista Investigative Site
    • Palm Desert, California, United States, 92260
      • KalVista Investigative Site
    • Palo Alto, California, United States, 94303
      • KalVista Investigative Site
    • Sacramento, California, United States, 95819
      • KalVista Investigative Site
    • Santa Ana, California, United States, 92705
      • KalVista Investigative Site
    • Tustin, California, United States, 92780
      • KalVista Investigative Site
  • Colorado
    • Golden, Colorado, United States, 80401
      • KalVista Investigative Site
  • Florida
    • Fort Myers, Florida, United States, 33912
      • KalVista Investigative Site
    • Miami, Florida, United States, 33126
      • KalVista Investigative Site
    • Miami, Florida, United States, 33143
      • KalVista Investigative Site
    • Pensacola, Florida, United States, 32503
      • KalVista Investigative Site
    • Winter Haven, Florida, United States, 33880
      • KalVista Investigative Site
  • Georgia
    • Augusta, Georgia, United States, 30909
      • KalVista Investigative Site
    • Marietta, Georgia, United States, 30060
      • KalVista Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • KalVista Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • KalVista Investigative Site
    • Boston, Massachusetts, United States, 02215
      • KalVista Investigative Site
  • Nevada
    • Henderson, Nevada, United States, 89052
      • KalVista Investigative Site
  • New York
    • Lynbrook, New York, United States, 11563
      • KalVista Investigative Site
    • Rochester, New York, United States, 14459
      • KalVista Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • KalVista Investigative Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • KalVista Investigative Site
  • Texas
    • Abilene, Texas, United States, 79606
      • KalVista Investigative Site
    • Arlington, Texas, United States, 76012
      • KalVista Investigative Site
    • Austin, Texas, United States, 78705
      • KalVista Investigative Site
    • Dallas, Texas, United States, 75231
      • KalVista Investigative Site
    • Fort Worth, Texas, United States, 76102
      • KalVista Investigative Site
    • San Antonio, Texas, United States, 78240-1502
      • KalVista Investigative Site
    • San Antonio, Texas, United States, 78240
      • KalVista Investigative Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • KalVista Investigative Site
  • Washington
    • Silverdale, Washington, United States, 98383
      • KalVista Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Procedure	Other: Sham Procedure; Sham Procedure
Experimental: KVD001 Injection (high dose)	Drug: KVD001 Injection; Intravitreal KVD001 Injection; Other Names: KVD001
Experimental: KVD001 Injection (low dose)	Drug: KVD001 Injection; Intravitreal KVD001 Injection; Other Names: KVD001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BCVA	Change from Baseline in Best Corrected Visual Acuity (BCVA)	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DRSS	Assessments of Diabetic Retinopathy Severity Score (DRSS, scale 10-85) to evaluate the percentage of eyes with a ≥2 step reduction in score from the baseline retinopathy severity as graded from fundus photography. Minimum and maximum values of the DRSS are 10 and 85, with the low end of the scale indicating absence of retinopathy which, as the score increases, so does the severity of the retinopathy such that a score of 85 is indicative of advanced proliferative diabetic retinopathy	16 weeks
CST	Assessments of Central Subfold Thickness (CST) - analysis of covariance of change from baseline in the study eye at week 16	16 weeks

Collaborators and Investigators

• Sponsor: KalVista Pharmaceuticals, Ltd.
• Investigators: Study Director: Study Director, KalVista Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Actual): October 10, 2019
• Study Completion (Actual): October 10, 2019

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: KVD001-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No