A Phase III, Randomized, Double-blind, Multiple Doses, Placebo-controlled, Parallel-group Adaptive Study to Evaluate the Efficacy and Safety of Atropine for the Treatment of Myopia Progression in Children and Adolescents (MODERATO Study)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 234
- 试验地点
- 16
- 主要终点
- Mean annual rate of progression of myopia
研究概览
简要总结
Myopia, or shortsightedness, is a multifactorial disorder, governed by environmental and genetic factors.
Myopia is the most common ocular disorder worldwide with an increasing prevalence over the past few decades and affecting the quality of life and economic health of individuals worsening socio-economic problems.
Progressive myopia is nearly exclusively a condition of childhood and adolescence, as in most young adults, myopia has stabilized.
Myopia frequently appears in childhood, with a peak incidence occurring between 8 and 10 years of age.
The most used topical pharmacological intervention for managing childhood myopia progression is atropine, a non-selective muscarinic antagonist, which has been widely used in clinical trials in concentrations ranging from 0.01% to 1.0%.
Atropine is at present the agent with the highest efficacy and optimal safety profile to reduce myopia progression in children and adolescents.
MODERATO study, a phase III, prospective, multicentric, randomized, double blind, multiple doses, placebo-controlled parallel-group, adaptive study, aims to evaluate the efficacy and safety of 0.025% and 0.05% atropine eye drops in children and adolescents aged 3 to under 18 years old over a 24-month period, to understand its ability to manage and stop myopia getting worse. It will be conducted in 11 centers in Italy, Spain, Poland, the UK and Albania.
详细描述
The MODERATO study is a phase III, prospective, multicentric, randomized, double-blind, parallel group, adaptive, placebo-controlled trial. The study will be conducted in primary care and hospital settings in 3 European countries (Italy, Spain, Poland), in the UK and in Albania, involving a total of 11 centers.
The study hypothesis is that low dose (0.025% and 0.05%) of atropine eye drops will reduce the myopia progression in children and adolescents (3-18 years of age) compared with placebo eye drops, over 24 months.
A total of 234 participants from 5 countries will be estimated to take part in the study.
Eligible participants with myopia with a spherical equivalent refraction of both eyes at least -0.75 D at baseline will be randomized to treatment (0.025% atropine eye drops, 0.05% atropine eye drops) and placebo groups in 1:1:1 ratio. Each arm will consist of at least 78 individuals.
In this study, the primary objective is to evaluate efficacy of 0.025% and 0.05% atropine eye drops in children and adolescents over 24 months to slow the progression of myopia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The study is designed as a double blinded clinical trial. During the trial, neither the participants nor the delegated staff will be aware of the group allocation. The 0.025% or 0.05% atropine eye drops and placebo eye drops will be prepared in a manner that will appear similar in appearance. The assignment of groups will not be disclosed to the subjects and the Investigators.
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, aged from 3 to less than 18 years.
- •Subjects showing myopia with a spherical equivalent refraction of both eyes at least -0.75 D at baseline.
- •The intraocular pressure in each eye must be equal or less than 21 mmHg.
- •The parents or the legal representative must be informed about the clinical trial and must sign the informed consent form. The exception to consider is related to the individuals aged above 16 years only in the UK, who can provide their own consent according to the local regulations.
- •Women with childbearing potential (WOCBP) (after menarche) who have a negative highly sensitive urine dipstick pregnancy test. Additional pregnancy testing during the study will be conducted at visits 1, 2, 3, 4, 5,
- •WOCBP or males who are using a highly effective birth control method to prevent pregnancies. Eligible highly effective contraceptive methods for WOCBP are combined (which contain estrogen and progestogen) hormonal contraception associated with inhibition of ovulation (oral, intravaginal (inside of the vagina), transdermal (through the skin)); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (small devices that are placed inside uterus to prevent pregnancies); intrauterine hormone-releasing system. Sexual abstinence represents a highly effective contraceptive method, if in line with the subject's normal habits.
排除标准
- •Anisometropia, meaning a significant difference in refractive power between the two eyes exceeding |1.5| D.
- •Refractive astigmatism exceeding |1.5| D.
- •Presence of ocular pathologies such as pathological myopia, corneal scars, or other anterior or posterior eye pathologies.
- •History of amblyopia or strabismus.
- •Presence of a history of a retinal dystrophy or systemic disorder that may predispose to severe myopia (e.g., Marfan syndrome, retinitis pigmentosa, Stickler syndrome, retinopathy of prematurity)
- •Abnormalities in ocular biometry, except for axial length or previous intraocular or ocular laser/non-laser surgery.
- •History of glaucoma or narrow angles in the anterior chamber of the eye.
- •Conditions such as Down syndrome or spastic paralysis.
- •Known intolerance or allergies to atropine eye drops or hypersensitivity to any component of the atropine eye drops.
- •Pregnancy or breastfeeding.
- •History of alcohol or drug abuse.
- •Mental or emotional instability that could interfere with study procedures.
- •Lack of reliability or cooperation from the patient.
- •Any treatment received for myopia within the past three months prior to inclusion in the study.
- •Other reasons, at the discretion of the investigator that may deem the subject's participation in the study inappropriate.
- •Patients who have consented to participate in the clinical trial, but do not meet one or more eligibility criteria required for participation in the trial during the screening procedures, and subsequently are not randomly assigned to the study treatment or entered in the study, are considered screening failures.
研究组 & 干预措施
Group 1
This group (N = 78 subjects) will be treated with 0.05% atropine eye drops
干预措施: 0.05% atropine eye drops (Drug)
Group 2
This group (N = 78 subjects) will be treated with 0.025% atropine eye drops
干预措施: 0.025% atropine eye drops (Drug)
Group 3
This group (N = 78 subjects) will be treated with placebo eye drops
干预措施: placebo eye drops (Drug)
结局指标
主要结局
Mean annual rate of progression of myopia
时间窗: 24 months
The primary outcome measure evaluates the efficacy of atropine in slowing myopia progression in children and adolescents. The mean annual rate of progression of myopia (D/year) based on spherical equivalent (SE) measured by cycloplegic autorefraction over 24 months.
次要结局
- Number and percentage of early escape patients.(6 months)
- Mean change in axial length and glasses prescription.(3, 6, 12, 18 and 24 months)
- Safety assessment of atropine.(3, 6, 12, 18 and 24 months)
- Use of photochromic and/or varifocal lenses.(3, 6, 12, 18, and 24 months)
- Changes in photosensitivity index.(Baseline, 3, 6, 12, 18, and 24 months)
- Best Corrected Visual Acuity.(3, 6, 12, 18, and 24 months)
- Pupil Diameter (PD) in photopic lighting condition.(3, 6, 12, 18, and 24 months)
- Accommodation amplitude.(3, 6, 12, 18, and 24 months)
- Vision-related quality of life (SREEQ-R).(Baseline, 6, 12 and 24 months)
- Vision-related quality of life (VLSQ-8).(Baseline, 6, 12 and 24 months)
- Acceptability of atropine formulation.(3, 6, 12, 18 and 24 months)
- Overall between-group difference from baseline in the proportion of subjects who show < -0.50 D myopia progression (Spherical Equivalent Refraction, SER).(24 months)