Study Evaluating the Efficacy and Safety of Chloroprocaine HCl Ophthalmic Gel 3% vs Proparacaine Ophthalmic Solution 0.5% Plus Subconjunctival Lidocaine in Patients Undergoing Intravitreal Injections (Quell)

A Phase 4, Multisite, Randomized, Double-Masked, Well-Controlled Study Evaluating the Efficacy and Safety of Chloroprocaine HCl Ophthalmic Gel 3% vs Proparacaine Ophthalmic Solution 0.5% Plus Subconjunctival Lidocaine in Patients Undergoing Intravitreal Injections: The QUELL Study

This Phase 4, multicenter, randomized, double-masked clinical study evaluates the efficacy and safety of chloroprocaine hydrochloride ophthalmic gel 3% (IHEEZO) compared with routine anesthesia (topical proparacaine 0.5% combined with subconjunctival lidocaine 2%) for ocular surface anesthesia during intravitreal injection procedures. Adult participants scheduled to undergo unilateral intravitreal injection of an FDA-approved anti-vascular endothelial growth factor (anti-VEGF) agent for retinal conditions will be randomized in a 1:1 ratio to receive either IHEEZO with a sham subconjunctival procedure or routine anesthesia.

The primary objective is to determine whether IHEEZO is non-inferior to routine anesthesia in achieving successful ocular surface anesthesia, defined as a participant-reported pain score of 0 or 1 (on a 0-5 ordinal pain scale) immediately before and immediately after intravitreal injection. Secondary outcomes include individual and cumulative pain scores, change from baseline in dry eye symptoms measured by the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, and ocular safety assessments through Day 7 follow-up.

Study Overview

• Status: Enrolling by invitation
• Conditions: Retinal Vein Occlusion; Age-Related Macular Degeneration (AMD); Diabetic Macular Edema (DME); Diabetic Retinopathy (DR)
• Intervention / Treatment: Drug: Chloroprocaine Ophthalmic Gel 3% (IHEEZO); Procedure: Sham Subconjunctival Injection; Drug: Proparacaine Hydrochloride Ophthalmic Solution 0.5%; Drug: Lidocaine Hydrochloride Injection 2%

Detailed Description

This is a prospective, multicenter, randomized, double-masked, controlled Phase 4 clinical trial evaluating the non-inferiority of chloroprocaine hydrochloride ophthalmic gel 3% (IHEEZO) compared with routine anesthesia (topical proparacaine 0.5% plus subconjunctival lidocaine 2%) for ocular surface anesthesia during intravitreal injection (IVT).

Adults scheduled to undergo unilateral intravitreal injection of an FDA-approved anti-vascular endothelial growth factor (anti-VEGF) agent for neovascular age-related macular degeneration, diabetic macular edema, retinal vein occlusion, or diabetic retinopathy will be randomized 1:1 to receive either IHEEZO with a sham subconjunctival procedure or routine anesthesia. Randomization will be stratified by clinical site and baseline ocular dryness severity (Standard Patient Evaluation of Eye Dryness [SPEED] score).

Participants in the experimental arm will receive three topical drops of chloroprocaine ophthalmic gel 3% followed by a sham subconjunctival procedure. Participants in the comparator arm will receive three topical drops of proparacaine 0.5% followed by subconjunctival lidocaine 2%. Standard antiseptic preparation with 5% povidone-iodine will be performed prior to IVT in both arms.

The primary endpoint is the proportion of participants achieving successful ocular surface anesthesia, defined as a pain score of 0 or 1 on a 0-5 ordinal pain scale both immediately before and immediately after IVT. Participants requiring rescue anesthesia prior to or during IVT will be considered treatment failures.

Secondary endpoints include individual and cumulative pain scores, change from baseline in SPEED questionnaire score, and ocular safety assessments including best-corrected visual acuity, intraocular pressure, corneal fluorescein staining (Oxford scale), and treatment-emergent adverse events through Day 7 (±2 days). Participants will be followed for approximately 7 days after injection.

• Study Type: Interventional
• Enrollment (Estimated): 236
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Tyler, Texas, United States, 75703
      • Tyler Retina Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to understand and voluntarily provide written informed consent prior to initiation of any study-specific procedures
• Male or female, age ≥ 18 years
• Scheduled to undergo unilateral, uncomplicated intravitreal injection of an FDA-approved, non-biosimilar anti-VEGF agent in the study eye
• Diagnosis requiring anti-vascular endothelial growth factor (anti-VEGF) treatment, including macular edema (cystoid or diabetic), retinal vein occlusion, diabetic retinopathy, or neovascular age-related macular degeneration
• At least three prior intravitreal anti-VEGF injections in the study eye
• Fewer than 13 intravitreal anti-VEGF injections in the study eye within the last 365 days
• Willing and able to comply with study procedures and follow-up assessments

Exclusion Criteria:

• Scheduled to undergo simultaneous bilateral intravitreal injection
• Pre-existing eye pain in the study eye
• Fewer than three prior intravitreal anti-VEGF injections in the study eye within 365 days prior to enrollment
• Mental disability or cognitive impairment that prevents reliable pain assessment
• Prisoner
• Pregnant or breastfeeding
• Woman of childbearing potential not using an acceptable method of contraception
• Inability to comply with study procedures or follow-up assessments
• Known sensitivity or allergy to any study medications or related drug classes
• History of resistance to local anesthetics
• History of Ehlers-Danlos syndrome
• Participation in another investigational drug or device study within 30 days prior to screening (unless previously randomized to a control group receiving Eylea, Eylea HD, Lucentis, or Vabysmo)
• Use of pain medication, opioids, analgesics, or NSAIDs (any route) within 24 hours prior to Visit 1
• Clinically significant systemic disease or condition that, in the Investigator's judgment, may compromise safety or study integrity
• Cataract extraction, intraocular surgery, or extraocular surgery within 60 days prior to enrollment that may affect ocular pain
• History of autoimmune disease, graft-versus-host disease, fibromyalgia, uveitis, neurotrophic corneal disease, keratitis or corneal ulceration, uncontrolled glaucoma, or herpetic ocular disease
• History of endophthalmitis or ocular trauma within 3 months prior to enrollment
• Pre-existing subconjunctival hemorrhage or bulbar conjunctival hyperemia
• Chronic ocular pain rated moderate to severe within 1 week prior to Visit 1
• Active bacterial or viral infection in either eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IHEEZO (Chloroprocaine Ophthalmic Gel 3%) + Sham Injection; Participants receive chloroprocaine hydrochloride ophthalmic gel 3% (IHEEZO) administered as 3 topical drops to the study eye approximately 1 minute apart prior to intravitreal injection. Approximately 5 minutes after the third drop, a sham subconjunctival injection (using a blunt cannula without conjunctival contact) is performed to maintain masking. Intravitreal injection is then administered per standard of care.	Drug: Chloroprocaine Ophthalmic Gel 3% (IHEEZO); Preservative-free chloroprocaine hydrochloride ophthalmic gel 3% administered as 3 topical drops to the study eye prior to intravitreal injection.; Procedure: Sham Subconjunctival Injection; Sham procedure performed using a syringe with a blunt-tipped cannula that does not contact the conjunctiva, performed to maintain masking prior to intravitreal injection.
Active Comparator: Routine Anesthesia (Proparacaine + Subconjunctival Lidocaine); Participants receive proparacaine hydrochloride ophthalmic solution 0.5% administered as 3 topical drops to the study eye approximately 1 minute apart prior to intravitreal injection. This is followed by a subconjunctival injection of lidocaine hydrochloride 2%. Intravitreal injection is then administered per standard of care.	Drug: Proparacaine Hydrochloride Ophthalmic Solution 0.5%; Topical proparacaine hydrochloride ophthalmic solution 0.5% administered as 3 drops to the study eye prior to intravitreal injection.; Drug: Lidocaine Hydrochloride Injection 2%; Subconjunctival injection of lidocaine hydrochloride 2% administered after topical proparacaine and prior to intravitreal injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving Successful Ocular Surface Anesthesia	Successful ocular surface anesthesia is defined as a participant-reported pain score of 0 (no pain/discomfort) or 1 (pressure only, no pain) at BOTH of the following timepoints: Immediately before intravitreal injection (after subconjunctival or sham injection), and; Immediately after intravitreal injection. Pain is assessed using a 0-5 descriptor-based ordinal scale: 0 = No pain/discomfort; = Pressure only, no pain; = Mild, brief sting/burn; tolerable; = Moderate discomfort; tolerable without rescue; = Marked pain; difficult to tolerate; = Severe/intolerable; procedure cannot continue without rescue Participants requiring rescue anesthesia at any time before or during intravitreal injection are considered treatment failures.	Immediately before and immediately after intravitreal injection (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score Immediately Before Intravitreal Injection	Pain is assessed using a 0-5 descriptor-based ordinal pain scale (minimum = 0, maximum = 5), where 0 indicates no pain and 5 indicates severe/intolerable pain. Higher scores indicate greater pain intensity.	Immediately before intravitreal injection (Day 1)
Pain Score Immediately After Intravitreal Injection	Pain is assessed using a 0-5 descriptor-based ordinal pain scale (minimum = 0, maximum = 5), where 0 indicates no pain and 5 indicates severe/intolerable pain. Higher scores indicate greater pain intensity.	Immediately after intravitreal injection (Day 1)
Pain Score at Evening Follow-Up	Participant-reported pain score assessed 3-12 hours after intravitreal injection. Pain is assessed using a 0-5 descriptor-based ordinal pain scale (minimum = 0, maximum = 5), where 0 indicates no pain and 5 indicates severe/intolerable pain. Higher scores indicate greater pain intensity.	Evening of Day 1 (3-12 hours post-injection)
Pain Score at 24 Hours Post-Injection	Participant-reported pain score assessed 20-28 hours after intravitreal injection. Pain is assessed using a 0-5 descriptor-based ordinal pain scale (minimum = 0, maximum = 5), where 0 indicates no pain and 5 indicates severe/intolerable pain. Higher scores indicate greater pain intensity.	Day 2 (20-28 hours post-injection)
Cumulative 24-Hour Pain Score	Sum of four pain assessments: pre-injection, post-injection, evening follow-up, and 24-hour follow-up. Each individual pain score ranges from 0 to 5; therefore, the cumulative 24-hour pain score ranges from 0 to 20. Higher scores indicate greater cumulative pain.	Day 1 through 24 hours post-injection
Change From Baseline in SPEED Questionnaire Score	Change from baseline in Standard Patient Evaluation of Eye Dryness (SPEED) total score. The SPEED questionnaire total score ranges from 0 to 28, with higher scores indicating greater dry eye symptom severity.	Baseline, Evening Day 1, and Day 2 (20-28 hours)
Change in Best-Corrected Visual Acuity	Best-corrected visual acuity measured using LogMAR visual acuity scale (minimum and maximum values dependent on chart range). Lower LogMAR values indicate better visual acuity.	Time Frame: Baseline and Day 7 ± 2 days
Change in Intraocular Pressure	Intraocular pressure measured in millimeters of mercury (mmHg). Higher values indicate higher intraocular pressure.	Time Frame: Baseline and Day 7 ± 2 days
Corneal Fluorescein Staining Score	Corneal staining graded using the Oxford Grading Scale (ordinal scale, minimum = 0, maximum = 5). Higher grades indicate greater corneal staining severity.	Time Frame: Baseline, post-injection Day 1, and Day 7 ± 2 days
Incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events	Time Frame: Day 1 through Day 7 ± 2 days Unit: Number of participants with ≥1 TEA

Collaborators and Investigators

• Sponsor: Harrow Inc
• Investigators: Principal Investigator: Samuel Minaker, MD, Tyler Retina Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Diabetes Mellitus; Eye Diseases; Diabetic Angiopathies; Diabetes Complications; Embolism and Thrombosis; Retinal Diseases; Retinal Degeneration; Venous Thrombosis; Thrombosis; Diabetic Retinopathy; Macular Degeneration; Retinal Vein Occlusion
• Other Study ID Numbers: IZ-4-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared. Harrow does not plan to make de-identified IPD available for secondary research purposes. IPD will not be available for access

Drug and device information, study documents

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