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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Harrow Inc
- 入组人数
- 236
- 试验地点
- 1
- 主要终点
- Proportion of Participants Achieving Successful Ocular Surface Anesthesia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
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.
干预措施: Chloroprocaine Ophthalmic Gel 3% (IHEEZO) (Drug)
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.
干预措施: Sham Subconjunctival Injection (Procedure)
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.
干预措施: Proparacaine Hydrochloride Ophthalmic Solution 0.5% (Drug)
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.
干预措施: Lidocaine Hydrochloride Injection 2% (Drug)
结局指标
主要结局
Proportion of Participants Achieving Successful Ocular Surface Anesthesia
时间窗: 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.
次要结局
- 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)
- Change From Baseline in SPEED Questionnaire Score(Baseline, Evening Day 1, and Day 2 (20-28 hours))
- Change in Best-Corrected Visual Acuity(Time Frame: Baseline and Day 7 ± 2 days)
- Change in Intraocular Pressure(Time Frame: Baseline and Day 7 ± 2 days)
- Corneal Fluorescein Staining Score(Time Frame: Baseline, post-injection Day 1, and Day 7 ± 2 days)
- Incidence of Treatment-Emergent Adverse Events(Time Frame: Day 1 through Day 7 ± 2 days Unit: Number of participants with ≥1 TEA)