The Study to YD312 Tablet in Patients With Diabetic Macular Edema

Multi-center, Randomized, Double-blind, Dose-finding, Phase 2a Clinical Trial to Evaluate the Effecacy and Safety of YD312 Tablet in Patients With Diabetic Macular Edema

This study objectives is to evaluate the efficacy of YD312 to improve visual acuity in patients with diabetic macular edema (DME) compared to placebo and determine optimal dose of phase 2b study.

Study Overview

• Status: Unknown
• Conditions: Diabetic Macular Edema(DME)
• Intervention / Treatment: Drug: YD312 50mg; Drug: YD312 150mg; Drug: YD312 350mg; Drug: Placebo

Detailed Description

These study results present the possibility that imatinib can be used as a new DME inhibiting agent by involving VEGF-independent ocular angiogenesis, not action points of existing agents, in effectively inhibiting excessive vascular angiogenesis observed in oxygen-induced retinopathy.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chung-gu
    • Daegu, Chung-gu, Korea, Republic of, 41944
      • Kyungpook National University Hospital
    • Daejeon-si, Chung-gu, Korea, Republic of, 35015
      • Chungnam National University Hospital
  • Gangmam-gu
    • Seoul, Gangmam-gu, Korea, Republic of, 06351
      • Samsung Medical Center
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06273
      • Kangnam Severance Hospital
  • Jin-gu
    • Busan, Jin-gu, Korea, Republic of, 47392
      • Inje National University Busan Park Hospital
  • Kyeonggi-do
    • Guri-si, Kyeonggi-do, Korea, Republic of, 11923
      • Hanyang University Guri Medical Center
    • Seongnam-si, Kyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• United States
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
  • Florida
    • Hialeah, Florida, United States, 33106
      • South Flolida Clinical Trials
    • Lakeland, Florida, United States, 33805
      • Florida Retina Consultants
  • Illinois
    • Chicago, Illinois, United States, 60126
      • Retina Associates
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina Group
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Impact Clinical Trials LV
  • New York
    • New York, New York, United States, 10022
      • NY Clinical Trials
  • Ohio
    • Painesville, Ohio, United States, 44077
      • Vitro-Retinal Consultants, Inc
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Phensylvania Retina Specialists
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch, LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Wagner Macula & Retina Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Screening Inclusion Criteria

   Study subjects must be eligible for the following criteria at screening:

   1. Subject who is male or female ≥ 19 years of age
   2. Subject who has a diagnosis of Type 1 or 2 diabetes
   3. Subject who has study eye with definite retinal thickening due to diabetic macular edema involving the center of the macula
   4. Subject who has voluntarily signed an informed consent form
2. Randomization Inclusion Criteria

Study eye must be eligible for the following criteria at randomization:

1. Subject who has study eye with central subfield thickness (CST) of ≥ 300 μm on optical coherence tomography (OCT)
2. Subject who has study eye with an early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) letter score ranging from 39 to 78, inclusive (approximate Snellen equivalent of 20/32 - 20/160)

Exclusion Criteria:

1. Subject who has study eye with any of the following criteria:

   1. Subject whose primary cause of macular edema is non-diabetic disease/condition (e.g., cataract extraction, vitreomacular interface abnormalities)
   2. Subject who is expected to have no improvement of decreased visual acuity in the opinion of investigator, even if macular edema is resolved (e.g., foveal atrophy, abnormal pigmentation, dense subfoveal hard exudate)
   3. Subject who has proliferative diabetic retinopathy.

   4. Subject who took the following within 3 months before randomization

      ① Focal/grid laser photocoagulation

      ② Intravitreal/circumbulbar corticosteroid, anti-VEGF and pro-VEGF (but, no wash-out period is required for the corticosteroid eyedrops)

   5. Subject who took panretinal photocoagulation (PRP) or intravitreal dexamethasone implant within 6 months before randomization
   6. Subject who has a history of vitrectomy
   7. Subject who took major ophthalmic surgeries (all intraocular surgeries including cataract extraction and scleral buckle) within 6 months before randomization
2. Subject who had systemic treatment of corticosteroid or anti-VEGF within 3 months before randomization.
3. Subject who administered vaccinium myrtillus extract or dobesilate calcium within 2 weeks before randomization
4. Subject who is suspected to require administration/treatment of drug/procedure that may affect the efficacy evaluation before the participation of clinical trial or during clinical trial (refer to '10.4 Combination Therapy and Contraindication').

5. Subject who has the following illness or abnormal laboratory test values:

   1. Subject who has a hypersensitivity to any excipients of the investigational product or similar class of drug and ingredient
   2. Subject who has uncontrolled hypertension (SBP > 160 mmHg or DBP >100 mmHg)
   3. Subject who has uncontrolled diabetes (HbA1c > 10.0%)
   4. Subject who has uncontrolled glaucoma in either eye (intraocular pressure (IOP) > 24 mmHg on medication or according to the investigator's judgment)
   5. ANC < 1.5 × 109/L
   6. Platelet < 125 × 109/L
   7. Total bilirubin > 1.5 × ULN
   8. AST or ALT > 2 × ULN

   9. Clcr* < 40 mL/min

      * Clcr (Cockcroft-Gault formula)

      = [(140 - age) x weight(kg) (x 0.85 for females)] / [72 x serum creatinine (Scr) (mg/dL)]

   10. Severe heart failure (NYHA class III/IV)
   11. Malignant tumor within 5 years before randomization
   12. Subject who is known to be HIV positive, is active hepatitis B patient or carrier, or is hepatitis C patient
   13. Ocular inflammatory diseases such as uveitis, conjunctivitis, and blepharitis in either eye. However, the participation of subject in this study is considered at the discretion of investigator.
   14. Unstable angina, myocardial infarction, transient ischemic attack, cerebral infarction, coronary artery bypass surgery, or transluminal coronary angioplasty within 6 months before screening

6. Pregnant woman, lactating woman, or female or male subject of childbearing potential

   *hormonal contraceptives, intrauterne contraceptive device, sterilization of spouse (e.g., vasectomy, tubal ligation), double-barrier method (e.g., combinational use of spermicides and condoms, diaphragm, contraceptive sponge, of FemCap)

7. Subject who took administraion/procedure of other investigational products or medical devices within longer period between 30 days before screening or over 5time half-life.
8. Subject, at the discretion of the investigator, who is unsuitable to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YD312 drug treatment; From the date when dispensed, investigational products will be dosed once a day at similar time to the first dosing time with meals and much water.	Drug: YD312 50mg; YD312 50mg * 1 + placebo 6 tablets; Drug: YD312 150mg; YD312 50mg * 3 + placebo 6 tablets; Drug: YD312 350mg; YD312 50mg * 7 tablets
Placebo Comparator: YD312 placebo drug treatment; From the date when dispensed, investigational products will be dosed once a day at similar time to the first dosing time with meals and much water.	Drug: Placebo; YD312 0mg * 7 tabets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in ETDRS BCVA latter score from baseline at Week 12 ( ETDRS chart reading at least 3 letters)	BCVA ERDRS measure at V1(screening), V2(baseline,week0), V3(week4), V4(week8), V5(week12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ETDRS BCVA latter score from baseline at Weeks 4 and 8		BCVA ERDRS measure at V1(screening), V2(baseline,week0), V3(week4), V4(week8), V5(week12)
Improvement or worsening rate of ETDRS BCVA from baseline at Weeks 4, 8, and 12	Proportion of improved subjects: ≥ 1 letter score increase, ≥ 10 letter score increase, ≥ 15 letter score increase; Proportion of worsened subjects: ≥ 5 letter score decrease, ≥ 10 letter score decrease, ≥ 15 letter score decrease	BCVA ERDRS measure at V1(screening), V2(baseline,week0), V3(week4), V4(week8), V5(week12)
Change in CST from baseline at Weeks 4, 8, and 12		BCVA ERDRS measure at V1(screening), V2(baseline,week0), V3(week4), V4(week8), V5(week12)

Collaborators and Investigators

• Sponsor: YD Global Life Science Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Actual): July 27, 2018
• Study Completion (Anticipated): March 20, 2020

Study Registration Dates

• First Submitted: August 14, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Clinicaltrial, DME, DR, AMD, imatinib mesylate
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema
• Other Study ID Numbers: YD312-01-P2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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