The Effectiveness and Safety of Two Low-concentration Atropine Sulfate Eye Drops (0.01%/0.02%) for Delaying the Pediatric Myopia Progression

Official title

The Effectiveness and Safety of Two Low-concentration Atropine Sulfate Eye Drops (0.01%/0.02%) for Delaying the Progression of Myopia in Children and Adolescents in a Randomized, Double-blind, Placebo Parallel-controlled, Multicenter, Phase III Clinical Trial

Overview

The clinical trial aims to test the effectiveness and safety of two low-dose atropine sulfate eye drops for delaying myopia progression in children and adolescents. Primary Objective: evaluate the effectiveness of 0.01% and 0.02% atropine sulfate eye drops for 96 weeks compared to placebo in delaying myopia progression in children and adolescents. Secondary Objective: evaluate the safety of two low-concentration atropine sulfate eye drops (0.01%/0.02%) in delaying myopia progression in children and adolescents. Exploratory Objective: 1. the efficacy and safety of two low-concentration atropine sulfate eye drops (0.01%/0.02%) for 144 weeks. 2. evaluate the rebound effect of two low-concentration atropine sulfate eye drops (0.01%/0.02%) after discontinuation.

Interventions

• Drug Atropine sulfate eye drops 0.01%
  Drug: 0.01% atropine sulfate eye drops Dosage form and strength: 0.01% (0.4 mL: 0.04 mg) eye drops Usage: both eyes, 1 drop in each eye, once a day, every night before sleep, gently press the dacryocyst on both sides for about 1 minute.
• Drug Atropine sulfate eye drops 0.02%
  Drug: 0.02% atropine sulfate eye drops Dosage form and strength: 0.02% (0.4 mL: 0.08 mg) eye drops Usage: both eyes, 1 drop in each eye, once a day, every night before sleep, gently press the dacryocyst on both sides for about 1 minute.
• Drug Placebo eye drops
  Drug: placebo eye drops Dosage form and strength: 0.4 mL eye drops Usage: both eyes, 1 drop in each eye, once a day, every night before sleep, gently press the dacryocyst on both sides for about 1 minute.

Primary outcome measures

• Effective change from baseline in equivalent spherical refraction at Week 96 visit [Time frame: At the Week 96 visit]

Secondary outcome measures (9)

• Effective change from baseline in eye axis length at 24 months [Time frame: At the Week 96 visit]
• Effective change from baseline in refraction at 12 months [Time frame: At the Week 48 visit]
• Effective change from baseline in ocular axis length at 12 months [Time frame: At the Week 48 visit]
• Progression of refraction ≤0.50 D at 12 months and 24 months and percentage [Time frame: At the Week 48 and Week 96 visits]
• Progression of refraction ≤0.75D at 12 months and 24 months and percentage [Time frame: At the Week 48 and Week 96 visits]
• Progression of refraction ≤1.00D at 12 months and 24 months and percentage [Time frame: At the Week 48 and Week 96 visits]
• Progression of refraction >1.00D at 12 months and 24 months and percentage [Time frame: At the Week 48 and Week 96 visits]
• Percentage of patients with 30% and 50% reduction in myopia progression at 12 and 24 months [Time frame: At the Week 48 and Week 96 visits]
• Change from baseline in other ocular morphologic measures at 12 months and 24 months [Time frame: At the Week 48 and Week 96 visits]

Eligibility criteria

Inclusion criteria

• The legal guardian of the subject voluntarily signed the written informed consent, and the subject over 8 years is required to sign the written informed consent voluntarily.
• Patients with myopia aged 6 to 12 years, including cut-offs.
• The equivalent spherical refraction ranges from -1.00 D to -4.00 D (automatic optometry under a cycloplegia condition) in both myopia eyes at inclusion screening.
• The astigmatism of both eyes was ≤ 1.50 D under a cycloplegia condition at inclusion screening.
• The antimetropia (measured by equivalent spherical refraction) is < 2.00 D at inclusion screening.
• Able to comply with study requirements, attend all study visits (including telephone visits), and be willing to receive random grouping of atropine treatment or placebo.

Exclusion criteria

• Allergic to this product or its excipients.
• Suffering from eye diseases that may affect vision (e.g. lens diseases such as cataracts, glaucoma, fundus macular disease, keratopathy, uveitis, retinal detachment, severe vitreous opacity, etc., manifest strabismus, nystagmus, ocular acute inflammatory disease), history of recurrent chronic ocular inflammation, or any other ocular pathology (e.g., angular stenosis, shallow anterior chamber).
• Intraocular pressure of either eye is > 21 mmHg or <10 mmHg at screening.
• Use of low-concentration (0.05% and below) atropine sulfate eye drops (including various in-hospital preparations, except for test drugs) and orthokeratology lenses (OK lenses) within 6 months before the screening.
• Use of other myopia control methods such as instruments (multifocal glasses, progressive multifocal glasses, etc.), medications (the use of cycloplegic agents for examinations such as optometry is allowed), and others (including traditional Chinese medicine, auricular acupuncture, massage, accommodative flippers, red light therapy instrument, etc.) within 3 months before screening.
• Those who have participated in other clinical trials and received drug or medical device interventions within 3 months before screening.
• Systemic or topical use of drugs that affect the efficacy evaluation, such as anticholinergics: atropine, pirenzepine, etc., and cholinomimetics: pilocarpine, etc. within 1 week before screening.
• Combined with severe immune system disease, central nervous system disease, Down syndrome, asthma, cardiopulmonary insufficiency, liver and kidney dysfunction, etc.
• Surgical intervention (ocular or systemic) within 6 months before screening, or planned surgery during the study.
• Heart rate sustained (more than 10 minutes) greater than 120 beats/min at screening (after 10 minutes of rest if the ECG shows a heart rate greater than 120 beats per minute, the ECG should be retested 10 minutes later. If the retest result below 120 beats/min, the screening is successful; If the retest result is still >120 beats/min, screening failed).
• Need for ocular use or systemic oral corticosteroids during the study. Intranasal, inhaled, topical cutaneous, intra-articular, perianal steroids, and short-term oral steroids (i.e., continuous use for < 2 weeks).
• Other conditions that are considered unsuitable by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 25 centers

• Hefei Maternal and Child Health Hospital — Hefei
• The Second Hospital of Anhui Medical University — Hefei
• Xuancheng People's Hospital — Xuancheng
• The Second Hospital of Lanzhou University — Lanzhou
• Liuzhou People's Hospital — Liuzhou
• The People's Hospital of Guangxi Zhuang Autonomous Region — Nanning
• The Affiliated Hospital of Guizhou Medical University — Guiyang
• The First People's Hospital of Zunyi — Zunyi
• … and 17 more centers

Identifiers

NCT: NCT06708156 · CTR20240786 · CTR20240786

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20240786 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗