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

NCT07456826 | Recruiting Phase 4 FDA Drug

• 1 other identifier: IZ-4-002
• Study Type: interventional
• Target: 236
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Macular Edema (DME); Age-Related Macular Degeneration (AMD); Retinal Vein Occlusion; Diabetic Retinopathy (DR)

Outcome Measures

Primary Outcomes (1)

• 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: 1. Immediately before intravitreal injection (after subconjunctival or sham injection), and 2. Immediately after intravitreal injection. Pain is assessed using a 0-5 descriptor-based ordinal scale: 0 = No pain/discomfort 1. = Pressure only, no pain 2. = Mild, brief sting/burn; tolerable 3. = Moderate discomfort; tolerable without rescue 4. = Marked pain; difficult to tolerate 5. = 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 Outcomes (10)

• Pain Score Immediately Before Intravitreal Injection

  Immediately before intravitreal injection (Day 1)

• Pain Score Immediately After Intravitreal Injection

  Immediately after intravitreal injection (Day 1)

• Pain Score at Evening Follow-Up

  Evening of Day 1 (3-12 hours post-injection)

• Pain Score at 24 Hours Post-Injection

  Day 2 (20-28 hours post-injection)

• Cumulative 24-Hour Pain Score

  Day 1 through 24 hours post-injection

Study Arms (2)

IHEEZO (Chloroprocaine Ophthalmic Gel 3%) + Sham Injection

EXPERIMENTAL

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); Procedure: Sham Subconjunctival Injection

Routine Anesthesia (Proparacaine + Subconjunctival Lidocaine)

ACTIVE COMPARATOR

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%; Drug: Lidocaine Hydrochloride Injection 2%

Interventions

Chloroprocaine Ophthalmic Gel 3% (IHEEZO) DRUG

Preservative-free chloroprocaine hydrochloride ophthalmic gel 3% administered as 3 topical drops to the study eye prior to intravitreal injection.

IHEEZO (Chloroprocaine Ophthalmic Gel 3%) + Sham Injection

Sham Subconjunctival Injection PROCEDURE

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.

IHEEZO (Chloroprocaine Ophthalmic Gel 3%) + Sham Injection

Proparacaine Hydrochloride Ophthalmic Solution 0.5% DRUG

Topical proparacaine hydrochloride ophthalmic solution 0.5% administered as 3 drops to the study eye prior to intravitreal injection.

Routine Anesthesia (Proparacaine + Subconjunctival Lidocaine)

Lidocaine Hydrochloride Injection 2% DRUG

Subconjunctival injection of lidocaine hydrochloride 2% administered after topical proparacaine and prior to intravitreal injection.

Routine Anesthesia (Proparacaine + Subconjunctival Lidocaine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Harrow Inc: lead

Study Sites (1)

Tyler Retina Research Institute

Tyler, Texas, 75703, United States

RECRUITING

MeSH Terms

Conditions

Macular Degeneration; Retinal Vein Occlusion; Diabetic Retinopathy

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Samuel Minaker, MD

  Tyler Retina Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Long

CONTACT

903-597-4644; mlong@tylerretina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 9, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)