E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028651 |
E.1.2 | Term | Myopia |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of SYD-101 for slowing the progression of myopia in children. To evaluate the safety and tolerability of SYD-101 |
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E.2.2 | Secondary objectives of the trial |
To evaluate the persistence of effect of SYD-101. To evaluate if the use of SYD-101 eyedrops may affect the QOL of the participant. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants must meet all of the inclusion criteria to be included in the study: 1. Parent/guardian has the ability to understand the study informed consent form (ICF) and agrees to sign the ICF prior to initiation of any protocol-related procedures; participant has the ability to give assent, as applicable, at the time of parental/guardian consent. 2. Participant is male or female between 3 and 14 years of age (inclusive) at the time of Screening. 3. Participant and parent/guardian are willing and able to comply with study instructions, study visits, and procedures. 4. Participant (or parent/guardian) has demonstrated ability to administer artificial eyedrops at the Screening or Baseline visit. 5. Participant is in good general health, with no clinically significant findings based on medical history and vital signs, as determined by the investigator at the time of Screening. 6. Postmenarchal female participants must have negative urine pregnancy test results. The following inclusion criteria (#7 through #11) are required of both eyes: 7. Refractive error by cycloplegic autorefraction at the baseline visit: a) Myopia of 0.50 D to 6.00 D (inclusive) b) Astigmatism ≤1.50 D c) Anisometropia ≤1.00 D 8. If the baseline myopia (SE) is <0.75 D, participant must have a history of myopia progression of 0.50 D in the previous 6 to 12 months. 9. If baseline myopia (SE) is ≥0.75 D, participant must be wearing refractive correction (single vision eyeglasses or soft, daily-wear, single-vision contact lenses) that meets the following criteria: a) Myopia (SE) corrected to within ±0.50 D of the investigator’s cycloplegic measurement of refractive error. b) Cylinder power must be within ±0.50 D of the investigator’s standard refraction technique, which can be based on a cycloplegic or non-cycloplegic refraction. c) Cylinder axis must be within ±5 degrees of the axis found on the investigator’s standard refraction when cylinder power is ≥1.00 D or within ±15 degrees when the cylinder power is <1.00 D. 10. BCVA of 75 letters (Snellen equivalent 20/32) or better. 11. Normal IOP <21 mmHg. |
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E.4 | Principal exclusion criteria |
Participants who meet any of the exclusion criteria will be excluded from the study: 1. Participant is a female who is pregnant, lactating, or intending to become pregnant within next 4 years. 2. Participant has a known allergy or hypersensitivity to atropine or any of the components of SYD-101. 3. Participant has history or current evidence of a medical condition predisposing the participant to degenerative myopia (eg, Marfan syndrome, Stickler syndrome) or a condition that may affect visual function or development (eg, diabetes mellitus, chromosome anomaly). 4. One or more biological parents with a history of myopia ≥9.00 D 5. Current use of a monoamine oxidase inhibitor 6. History of, or currently receiving treatment for, any systemic infection or autoimmune disease considered serious by the investigator 7. Participation in an investigational drug or device study within 30 days prior to Screening 8. Evidence of any ocular inflammation or infection in either eye, including blepharitis, conjunctivitis, keratitis, and scleritis 9. History or evidence of the following in either eye: a) Retinopathy of prematurity b) Abnormal refractive anatomy (eg, keratoconus, lenticonus, spherophakia) c) Amblyopia, manifest strabismus, or nystagmus 10. Use of any of the following (previously, currently, or plans to do so in the future): a) Orthokeratology (orthoK), rigid gas-permeable, bifocal, progressive-addition, multi-focal, or other lenses to reduce myopia progression. b) Use of atropine, pirenzepine, or other anti-muscarinic agent for myopia 11. History or evidence of any ocular surgery or planned future ocular surgery in either eye 12. History or current evidence of ocular disease in the either eye that, in the opinion of the investigator, may confound assessment of visual acuity and/or refraction 13. Unwillingness or inability to comply with study requirements and restrictions, including but not limited to those specified in Section 5.3 (eg, required conversion from extended wear lenses to daily wear lenses, full-time use of contact lenses or spectacles) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy End Point for EU: • The annual progression rate of myopia through Month 24
Safety Endpoints: • Evaluation of AEs and SAEs • Changes from baseline in vital sign measurements • Mean change from baseline in pupil diameter • Mean change from baseline in binocular accommodative amplitude • Changes from baseline in findings detected by best-corrected visual acuity (BCVA), biomicroscopy, intraocular pressure (IOP), and ophthalmoscopy • Changes from baseline in corneal endothelial cell count (selected sites only; approximately 25% of study participants) • Tolerability to the masked study drug will be solicited via questionnaire • Pregnancy test results (female participants of childbearing potential only) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis of safety and efficacy data will be performed at Month 24, Month 36, and Month 48.
For regulatory submission in the European Union (EU) endpoints will be analyzed as requested by the respective regulatory authorities.
Adverse events will be monitored throughout the study beginning at the time of informed consent. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints: 1. Proportion of participants with myopic progression >0.75 D at or before Month 24 2. Proportion of participants with annual myopia progression rate through Month 24 ≤0.50 D/year 3. Proportion of participants with annual myopia progression rate through Month 24 ≤0.25 D/year 4. Proportion of participants with increase of myopia of >0.50 D at or before Month 24 5. Time to progression of myopia of >0.75 D through Month 24 6. Mean annual progression rate using Month 24 data on Subgroup of participants with refractive history of progression ≥ 0.5D 7. Mean annual progression rate using Month 24 data on Subgroup of participants with refractive history of progression ≥ 0.75D 8. Mean change from baseline in axial length at Month 24
Exploratory Endpoints: • Mean change from baseline in SE at Month 48 (ie, 12 months after randomized withdrawal) • Mean time spent on various activities will be solicited via questionnaire • Proportion of agreement to QOL statements |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last study visit of the last subject.
A participant is considered to have completed the study if s/he has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Activities (SOA).
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 10 |