A Phase IIb Safety and Efficacy Study of DE-126 Ophthalmic Solution in Primary Open-Angle Glaucoma or Ocular Hypertension- Angel Study

A Phase IIb, Randomized, Observer-Masked, Placebo- and Active-Controlled, Parallel-Group, Multinational and Multicenter Study Assessing the Safety and Efficacy of DE-126 Ophthalmic Solution in Subjects With Primary Open-Angle Glaucoma or Ocular Hypertension- Angel Study

Treatment of elevated pressure in the eye (Intraocular pressure, or 'IOP') with eye drop medications has been shown to be effective in delaying or preventing the progression of glaucoma, and it is the only proven method for reducing the risk of glaucomatous visual field loss.

This study is being conducted to determine how well DE-126 ophthalmic solution works (efficacy) in safely lowering IOP when dosed as topical eyedrops. This study will evaluate the safety and efficacy of four (4) concentrations of DE-126, when compared with latanoprost (0.005%) eye drops in patients with primary open-angle glaucoma or ocular hypertension.

The IOP will be measured at 3 different times throughout the day, over 6 total visits during a 3-month treatment period (with up to 4 extra weeks observation if the patient must stop taking current eye drops to lower IOP). Safety assessments will be done throughout the study, including ocular signs and symptoms, vital signs, and clinical laboratory tests. While the most important time-point to measure IOP in this study and evaluate efficacy will be at the final study visit (month 3), IOP values will also be evaluated at other visits throughout the 3-month treatment period.

Study Overview

• Status: Completed
• Conditions: Open-angle Glaucoma, Ocular Hypertension
• Intervention / Treatment: Drug: Vehicle of DE-126 Ophthalmic Solution, high dose of DE-126 Ophthalmic Solution; Drug: Topical ultra-low dose of DE-126 Ophthalmic Solution; Drug: Topical low dose of DE-126 Ophthalmic Solution; Drug: Topical medium dose of DE-126 Ophthalmic Solution; Drug: Topical high dose of DE-126 Ophthalmic Solution; Drug: 0.005% Latanoprost Ophthalmic Solution

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Fukuoka, Japan
    • Murakami Karindoh Hospital
  • Nagoya-shi, Aichi, Japan
    • Nagasaka Eye Clinic
  • Osaka-shi, Osaka, Japan
    • Sugiura Eye Clinic
  • Sapporo-shi, Hokkaido, Japan
    • Sapporo Katoh Ophthalmology Clinic
  • Shibuya-ku, Tokyo, Japan
    • Dogenzaka Kato Eye Clinic
• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center, Inc
    • Mission Hills, California, United States, 91345
      • North Valley Eye Medical Group
    • Newport Beach, California, United States, 92657
      • Eye Research Foundation, INC
    • Petaluma, California, United States, 94954
      • North Bay Eye Associates, Inc.
  • Florida
    • Largo, Florida, United States, 33773
      • Shettle Eye Research, Inc.
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Clayton Eye Clinical Research, LLC
    • Roswell, Georgia, United States, 30076
      • Coastal Research Associates, LLC
  • New York
    • Rochester, New York, United States, 14618
      • Rochester Ophthalmological Group, PC
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Mundorf Eye Center
    • High Point, North Carolina, United States, 27262
      • Cornerstone Health Care, LLC
  • Texas
    • Austin, Texas, United States, 78731
      • Keystone Research Ltd SMO/Texan Eye, PA
    • San Antonio, Texas, United States, 78240
      • Keystone Research LTD SMO/Medical Center Ophthalmology Assoc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide signed written informed consent
• Diagnosis of POAG or OHT in both eyes
• Qualifying corrected visual acuity in each eye
• Qualifying central corneal thickness in each eye
• Qualifying Day 1 IOP measurement at 3 time-points in both eyes
• Qualifying Anterior chamber angle

Exclusion Criteria:

• History of ocular surgery specifically intended to lower IOP
• Subjects who cannot safely discontinue use of ocular hypotensive medications during the wait/washout period
• Advanced glaucoma in either eye
• Any corneal abnormality or other condition interfering with or preventing reliable Goldmann applanation tonometry
• Any ocular surgery or ocular laser treatment within 90 days prior to Visit 1 (Screening) and throughout the study in either eye
• Females who are pregnant, nursing, or planning a pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (Vehicle of DE-126) followed by high dose of DE-126	Drug: Vehicle of DE-126 Ophthalmic Solution, high dose of DE-126 Ophthalmic Solution; Vehicle of DE-126 Ophthalmic Solution dosed once daily for 6weeks, followed by high dose of DE-126 dosed once daily for 6 additional weeks
Experimental: Ultra-low dose 0.0005% DE-126	Drug: Topical ultra-low dose of DE-126 Ophthalmic Solution; Topical ultra-low dose of DE-126 Ophthalmic Solution dosed once daily for 12 weeks
Experimental: Low dose 0.001% DE-126	Drug: Topical low dose of DE-126 Ophthalmic Solution; Topical low dose of DE-126 Ophthalmic Solution dosed once daily for 12 weeks
Experimental: Medium dose 0.002% DE-126	Drug: Topical medium dose of DE-126 Ophthalmic Solution; Topical medium dose of DE-126 Ophthalmic Solution dosed once daily for 12 weeks
Experimental: High dose 0.003% DE-126	Drug: Topical high dose of DE-126 Ophthalmic Solution; Topical high dose of DE-126 Ophthalmic Solution dosed once daily for 12 weeks
Active Comparator: 0.005% Latanoprost	Drug: 0.005% Latanoprost Ophthalmic Solution; 0.005% Latanoprost Ophthalmic Solution dosed once daily for 12 weeks; Other Names: Xalatan®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular Pressure in the Study Eye at Month 3	Intraocular Pressure (IOP),the fluid pressure inside the eye was measured by the Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time-points throughout the day.	9:00, 13:00 and 17:00 at Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular Pressure in the Study Eye at Week 6	Intraocular Pressure (IOP),the fluid pressure inside the eye was measured by the Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time-points throughout the day.	9:00, 13:00 and 17:00 at Week 6
Intraocular Pressure in the Study Eye at Week 1 and Week 2	Intraocular Pressure (IOP),the fluid pressure inside the eye was measured by the Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time-points throughout the day.	9:00, 13:00 and 17:00 at Week 1 and Week 2
Mean Diurnal Intraocular Pressure in the Study Eye at Each Post-baseline Visit	Mean Diurnal IOP was defined as the mean of the IOP values at the three schedules timepoints (9:00, 13:00 and 17:00) at that visit for that subject.	Week 1, Week 2, Week 6 and Month 3.
Change From Baseline (CFB) in Mean Diurnal Intraocular Pressure in the Study Eye at Each Post-baseline Visit	Mean Diurnal IOP was defined as the mean of the IOP values at the three schedules timepoints (9:00, 13:00 and 17:00) at that visit for that subject.	Week 1, Week 2, Week 6 and Month 3.
Percent Change From Baseline (CFB) in Mean Diurnal Intraocular Pressure in the Study Eye at Each Post-baseline Visit	Mean Diurnal IOP was defined as the mean of the IOP values at the three schedules timepoints (9:00, 13:00 and 17:00) at that visit for that subject.	Week 1, Week 2, Week 6 and Month 3.
Change From Baseline (CFB) in Intraocular Pressure in the Study Eye at Three Time Points at Each Post-baseline Visit	Intraocular Pressure (IOP),the fluid pressure inside the eye was measured by the Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time-points throughout the day.	9:00, 13:00 and 17:00 at Week 1, Week 2, Week 6 and Month 3.
Percent Change From Baseline (CFB) in Intraocular Pressure in the Study Eye at Three Time Points at Each Post-baseline Visit	Intraocular Pressure (IOP),the fluid pressure inside the eye was measured by the Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time-points throughout the day.	9:00, 13:00 and 17:00 at Week 1, Week 2, Week 6 and Month 3.
Percentage of Subjects With Mean Diurnal Intraocular Pressure Reduction From Baseline ≥ 20%, 25% and 30% in the Study Eye at Each Post-baseline Visit	A Subject was a responder if the percent reduction from baseline in mean diurnal IOP in the study eye was ≥ 20%. A Subject was a responder if the percent reduction from baseline in mean diurnal IOP in the study eye was ≥ 25%. A Subject was a responder if the percent reduction from baseline in mean diurnal IOP in the study eye was ≥ 30%.	WeeK 1, Week 2, Week 6 and Month 3.
Percentage of Subjects With Mean Diurnal Intraocular Pressure ≤ 18 mmHg in the Study Eye at Each Post-baseline Visit	A subject was a responder if the mean diurnal IOP in the study eye was ≤ 18 mmHg.	Week 1, Week 2, Week 6 and Month 3.

Collaborators and Investigators

• Sponsor: Santen Inc.

Publications and helpful links

General Publications

• Wirta DL, Kuwayama Y, Lu F, Shao H, Odani-Kawabata N. Phase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study. J Ocul Pharmacol Ther. 2022 Apr;38(3):240-251. doi: 10.1089/jop.2021.0077. Epub 2022 Feb 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Actual): February 27, 2018
• Study Completion (Actual): February 27, 2018

Study Registration Dates

• First Submitted: July 11, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2020
• Last Update Submitted That Met QC Criteria: September 30, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Glaucoma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Ophthalmic Solutions; Pharmaceutical Solutions; Latanoprost
• Other Study ID Numbers: 012601IN

Drug and device information, study documents

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