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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myopia; Myopia Progression
• Intervention / Treatment: Drug: Atropine sulfate eye drops 0.01%; Drug: Atropine sulfate eye drops 0.02%; Drug: Placebo eye drops

• Study Type: Interventional
• Enrollment (Estimated): 606
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Liang Gao; Phone Number: 0086-15056564539; Email: 9071044822@qq.com
• Study Contact Backup: Name: Shaolong XUE, Dr.; Phone Number: 0086-18565027687; Email: xuesl@seefunge.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Yueguo Chen
  • Beijing, China
    • Recruiting
    • Beijing Tongren Hospital Affiliated to Capital Medical University
    • Contact: Feng Wu; Phone Number: 0086-15910961255; Email: bjtrec@126.com
    • Contact: Ningli Wang, Postdoctoral
  • Chongqing, China
    • Recruiting
    • Chongqing Aier Eye Hospital
    • Contact: Yi Ren
  • Shanghai, China
    • Recruiting
    • Shanghai Eye Disease Prevention and Treatment Center (Shanghai Eye Hospital)
    • Contact: Wei Xu
    • Contact: Haidong Zou
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Eye Hospital
    • Contact: Lin Liu
  • Anhui
    • Hefei, Anhui, China
      • Recruiting
      • The Second Hospital of Anhui Medical University
      • Contact: Liming Tao
    • Hefei, Anhui, China
      • Recruiting
      • Hefei Maternal and Child Health Hospital
      • Contact: Ruqin Zha
    • Xuancheng, Anhui, China
      • Recruiting
      • Xuancheng People's Hospital
      • Contact: Shenghua Dong
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • The Second Hospital of Lanzhou University
      • Contact: Wanna Ren
  • Guangxi Zhuang Autonomous Region
    • Liuzhou, Guangxi Zhuang Autonomous Region, China
      • Recruiting
      • Liuzhou People's Hospital
      • Contact: Xiaobo Wan
    • Nanning, Guangxi Zhuang Autonomous Region, China
      • Recruiting
      • The People's Hospital Of Guangxi Zhuang Autonomous Region
      • Contact: Qi Chen
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Hao Gu
    • Zunyi, Guizhou, China
      • Recruiting
      • The First People'S Hospital of Zunyi
      • Contact: Wei Tan
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Recruiting
      • Daqingshi People's Hospital
      • Contact: Xingmin Wang
  • Henan
    • Kaifeng, Henan, China
      • Recruiting
      • Kaifeng Central Hospital
      • Contact: Hongmei Mu
  • Hunan
    • Hengyang, Hunan, China
      • Recruiting
      • The First Affiliated Hospital of University of South China
      • Contact: Gang Tan
  • Jiangsu
    • Huai'an, Jiangsu, China
      • Recruiting
      • Huai'an first people's hospital
      • Contact: Chaopeng Li
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • The First Affiliated Hospital of Nanchang University
      • Contact: Xiaorong Wu
    • Nanchang, Jiangxi, China
      • Recruiting
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Xiaolong Yin
    • Nanchang, Jiangxi, China
      • Recruiting
      • Affiliated Eye Hospital of Nanchang University
      • Contact: Hongfei Liao
  • Shandong
    • Weifang, Shandong, China
      • Recruiting
      • Weifang Eye Hospital
      • Contact: Xianyong Sun
  • Shanxi
    • Changzhi, Shanxi, China
      • Recruiting
      • Heping Hospital Affiliated to Changzhi Medical College
      • Contact: Yun Cui
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi Eye Hospital
      • Contact: Junhong Li
    • Xianyang, Shanxi, China
      • Recruiting
      • Xianyang Hospital of Yan'an University
      • Contact: Binke Yu
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Lijun Shen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Patients with myopia aged 6 to 12 years, including cut-offs.
3. 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.
4. The astigmatism of both eyes was ≤ 1.50 D under a cycloplegia condition at inclusion screening.
5. The antimetropia (measured by equivalent spherical refraction) is < 2.00 D at inclusion screening.
6. 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:

1. Allergic to this product or its excipients.
2. 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).
3. Intraocular pressure of either eye is > 21 mmHg or <10 mmHg at screening.
4. 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.
5. 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.
6. Those who have participated in other clinical trials and received drug or medical device interventions within 3 months before screening.
7. 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.
8. Combined with severe immune system disease, central nervous system disease, Down syndrome, asthma, cardiopulmonary insufficiency, liver and kidney dysfunction, etc.
9. Surgical intervention (ocular or systemic) within 6 months before screening, or planned surgery during the study.
10. 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).
11. 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).
12. Other conditions that are considered unsuitable by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental group (0.01% atropine sulfate eye drops); 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 0.01%; 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.
Active Comparator: Experimental group (0.02% atropine sulfate eye drops); 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.
Placebo Comparator: Control group (placebo eye drops); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective change from baseline in equivalent spherical refraction at Week 96 visit	The inter-group difference in the value of change from baseline in equivalent spherical refraction after 0.01% or 0.02% atropine sulfate eye drops versus placebo under a cycloplegia condition at the Week 96 visit	At the Week 96 visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective change from baseline in eye axis length at 24 months	Value of change from baseline in eye axis length at 24 months of dosing (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 96 visit
Effective change from baseline in refraction at 12 months	Change from baseline in refraction (automatic optometric equivalent spherical refraction under a cycloplegia condition) at 12 months (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 visit
Effective change from baseline in ocular axis length at 12 months	Change from baseline in ocular axis length at 12 months of dosing (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 visit
Progression of refraction ≤0.50 D at 12 months and 24 months and percentage	Progression of refraction (automatic optometric equivalent spherical refraction under a cycloplegia condition) ≤0.50 D at 12 months and 24 months (0.02% atropine vs. placebo; 0.01% atropine vs. placebo) and percentage (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 and Week 96 visits
Progression of refraction ≤0.75D at 12 months and 24 months and percentage	Progression of refraction (automatic optometric equivalent spherical refraction under a cycloplegia condition) ≤0.75D at 12 months and 24 months and percentage (0.02% atropine vs placebo; 0.01% atropine vs placebo)	At the Week 48 and Week 96 visits
Progression of refraction ≤1.00D at 12 months and 24 months and percentage	Progression of refraction (automatic optometric equivalent spherical refraction under a cycloplegia condition) ≤1.00D at 12 months and 24 months (0.02% atropine vs. placebo; 0.01% atropine vs. placebo) and percentage (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 and Week 96 visits
Progression of refraction >1.00D at 12 months and 24 months and percentage	Progression of refraction (automatic optometric equivalent spherical refraction under a cycloplegia condition) >1.00D at 12 months and 24 months of dosing and percentage (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 and Week 96 visits
Percentage of patients with 30% and 50% reduction in myopia progression at 12 and 24 months	Percentage of patients with 30% and 50% reduction in myopia progression at 12 and 24 months of medication compared to control (0.02% atropine versus placebo; 0.01% atropine versus placebo)	At the Week 48 and Week 96 visits
Change from baseline in other ocular morphologic measures at 12 months and 24 months	Change from baseline in other ocular morphologic measures (e.g., corneal curvature, vitreous chamber depth, choroidal thickness) at 12 months and 24 months of dosing (0.02% atropine vs. placebo; 0.01% atropine vs. placebo)	At the Week 48 and Week 96 visits

Collaborators and Investigators

• Sponsor: Oupushifang Pharmaceutical Technology Co., Ltd.
• Collaborators: Seefunge Pharmaceutical Technology Co., Ltd.; AUTEK China Inc.
• Investigators: Principal Investigator: Ningli Wang, Postdoctoral, Beijing Tongren Hospital Affiliated to Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 24, 2024
• First Posted (Actual): November 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Myopia; Atropine
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Eye Diseases; Refractive Errors; Myopia; Disease Progression; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Pharmaceutical Solutions; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Mydriatics; Atropine; Ophthalmic Solutions
• Other Study ID Numbers: CTR20240786 (Registry Identifier: National Medical Products Administration, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No