Age-Related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), Retinal Vein Occlusion
Conditions
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.
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.
Interventions
DRUGChloroprocaine Ophthalmic Gel 3% (IHEEZO)
Preservative-free chloroprocaine hydrochloride ophthalmic gel 3% administered as 3 topical drops to the study eye prior to intravitreal injection.
PROCEDURESham 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.
DRUGProparacaine Hydrochloride Ophthalmic Solution 0.5%
Topical proparacaine hydrochloride ophthalmic solution 0.5% administered as 3 drops to the study eye prior to intravitreal injection.
DRUGLidocaine Hydrochloride Injection 2%
Subconjunctival injection of lidocaine hydrochloride 2% administered after topical proparacaine and prior to intravitreal injection.
Sponsors
Harrow Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving Successful Ocular Surface Anesthesia | Immediately before and immediately after intravitreal injection (Day 1) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Score Immediately Before Intravitreal Injection | Immediately before intravitreal injection (Day 1) | 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. |
| Pain Score Immediately After Intravitreal Injection | Immediately after intravitreal injection (Day 1) | 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. |
| Pain Score at Evening Follow-Up | Evening of Day 1 (3-12 hours post-injection) | 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. |
| Pain Score at 24 Hours Post-Injection | Day 2 (20-28 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. |
| Cumulative 24-Hour Pain Score | Day 1 through 24 hours post-injection | 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. |
| Change From Baseline in SPEED Questionnaire Score | Baseline, Evening Day 1, and Day 2 (20-28 hours) | 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. |
| Change in Best-Corrected Visual Acuity | Time Frame: Baseline and Day 7 ± 2 days | 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. |
| Change in Intraocular Pressure | Time Frame: Baseline and Day 7 ± 2 days | Intraocular pressure measured in millimeters of mercury (mmHg). Higher values indicate higher intraocular pressure. |
| Corneal Fluorescein Staining Score | Time Frame: Baseline, post-injection Day 1, and Day 7 ± 2 days | Corneal staining graded using the Oxford Grading Scale (ordinal scale, minimum = 0, maximum = 5). Higher grades indicate greater corneal staining severity. |
| Incidence of Treatment-Emergent Adverse Events | Time Frame: Day 1 through Day 7 ± 2 days Unit: Number of participants with ≥1 TEA | Incidence of Treatment-Emergent Adverse Events |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSamuel Minaker, MD
Tyler Retina Research Institute
Outcome results
None listed