| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Wet form of Neovascular Age-Related Macular Degeneration (AMD) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic eye disorder caused by abnormal proliferation of blood vessels through retina. Leading cause of blindness in elderly people. |
|
| 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 | LLT |
| E.1.2 | Classification code | 10075568 |
| E.1.2 | Term | Wet age-related macular degeneration |
| E.1.2 | System Organ Class | 100000004853 |
|
| 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 |
| The primary objective is to evaluate effect on visual acuity of SYL1801 sodium at three doses (5 mg/mL, 25 mg/mL and 50 mg/mL) when administered as 1 drop once a day for 42 days in subjects with neovascular AMD. |
|
| E.2.2 | Secondary objectives of the trial |
| Effect, tolerabity and safety of SYL1801 opthalmic solution on wet AMD and AE occurrence |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects need to meet ALL the following criteria:
1. Patient is a male or a female aged ≥ 50 years at screening visit.
2. Have given their written consent to participate in the study, after having received all information relating to the design, aims and possible risks resulting therefrom.
3. Presence of active subfoveal CNV (any subtype) or juxtafoveal CNV with leakage affecting the fovea secondary to AMD evidenced by FA at screening visit confirmed by the central reader.
4. Total area of CNV (including both classic and occult components) encompassed within the lesion and ≥ 50% of the lesion area measured by FA at screening visit as evaluated by the central reader.
5. Central Subfield Thickness >300μm measured by SD-OCT at screening visit as evaluated by the central reader.
6. Presence of intraretinal or subretinal fluid evidenced by SD-OCT suggestive of active CNV secondary to neovascular AMD at screening as evaluated by the central reader.
7. BCVA, using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, between 70 and 25 letters (20/40 to 20/320 Snellen equivalent in the study eye) at screening and baseline visit.
* Only one eye per patient will be used for effect assessment, as selected by the Investigator and confirmed by the central reader. If both eyes are eligible, the worst eye will be selected, as long as the counter eye does not require immediate treatment. If both eyes are equally affected, the right eye will be selected, as long as the counter eye does not require immediate treatment.
|
|
| E.4 | Principal exclusion criteria |
Subjects who meet ANY of the following criteria
Non-inclusion criteria related to general health:
1. Pregnant or breastfeeding females or females with a positive
pregnancy test at the screening visit.
2. Women of childbearing potential not willing to use a highly effective
contraceptive method as defined by protocol.
3. Current, previous chronic or recurrent condition which, according to
the Investigator, might impact the interpretation of the study results or
put the patient at risk.
4. Any concomitant treatment or prior ocular procedure or surgery, or
alteration of the dose of systemic medications at the time of entry into
the study that could interfere in the assessment of the trial in the
Investigator´s opinion. (List of not permitted medications and
procedures in Table 3). Any previous treatment for AMD including anti-
VEGF intravitreal injections is prohibited.
5. Clinically significant abnormalities indicating unstable or
deteriorating condition of the patient (as determined by the
Investigator) in laboratory tests at screening.
6. History of hypersensitivity to any component of the formulation or to
ophthalmic diagnostic agents.
7. Concurrent disease in the study eye, other than AMD (e.g., corneal
diseases and dystrophies, conjunctival diseases, eye lid abnormalities, or
any other diseases of the cornea and macula, or optic nerve
abnormality) that could confound interpretation of the results.
8. Prior or current history of diabetic retinopathy, diabetic macular
edema, or posterior uveitis, or retinal vein occlusion.
9. Patients who have previously been treated with systemic anti-VEGF
drugs or pro-VEGF treatments.
10. Use of contact lenses during the study.
11. Currently participating or having participated in another clinical
trial within the 2 months, or 5 study drug half-lives, whichever is longer,
prior to inclusion, excluding vitamins or food supplements studies.
Non-inclusion criteria related to lesion characteristics:
12. Subretinal haemorrhage in the study eye as confirmed by the
central reader, that either involved the center of the fovea, if the size of
the haemorrhage is ≥ 1 DA (disc area) in size ; or haemorrhage ≥ 50%
of the total lesion area.
13. Subfoveal fibrosis or atrophy in the study eye confirmed by the
central reader.
14. CNV in either eye due to other causes, such as ocular
histoplasmosis, trauma or pathologic myopia confirmed by the central
reader. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary objective is to evaluate effect on visual acuity of SYL1801
sodium at three doses (5 mg/mL, 25 mg/mL and 50 mg/mL) when
administered as 1 drop once a day for 42 days in subjects with
neovascular AMD.
The primary end point is the change from Baseline (Day 1, 1st
administration of IMP) to Visit 3 (after 42 days of treatment) in BCVA score based on ETDRS visual acuity chart. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary objective:
The secondary objective is to evaluate effect on visual acuity and disease
progression together with safety of SYL1801 sodium at three doses (5
mg/mL, 25 mg/mL and 50 mg/mL) when administered as 1 drop once a
day for 42 days in subjects with neovascular AMD.
Secondary endpoints:
‒ Proportion of patients within each cohort who maintained visual
acuity, defined as a loss of fewer than 15 letters in BCVA score based on
ETDRS chart from Baseline.
‒ Proportion of patients gaining at least 5, 8, 10, and 15 letters in BCVA
score based on ETDRS chart from baseline at Visit 3 (Day 43)
‒ Proportion of subjects within each cohort who received rescue
medication at Visits 1 through 3.
‒ Change from Baseline within each cohort on the size of CNV (Flow
Area) observed with OCT angiography (OCTA) at Visit 3 (Day 43) as
determined by the central reader.
‒ Change from Screening within each cohort on the size of CNV (total
classic CNV area) and amount of leakage from CNV (leakage area)
observed with fluorescein angiography (FA) at Visit 3 (Day 43) as
determined by the central reader.
‒ Changes from Baseline (Day 1) within each cohort in the following
Optical Coherence Tomography (SD-OCT)-observed biomarkers at Visit 3
(Day 43) as determined by the central reader:
o Presence and height/width of the largest cyst in central 1mm of
Intraretinal fluid (IRF)
o Presence and highest height/width of Subretinal fluid (SRF)
o Presence of drusenoid, vascular, or serous Pigment epithelial
detachments (PED)
o Central subfield thickness (CST)
o Disruption of external limiting membrane (ELM)
o Disruption of the ellipsoid zone (EZ)
Safety endpoints:
‒ Changes from Baseline (Day 1) in IOP, slit-lamp biomicroscopy and
dilated ophthalmoscopy at Visit 3 (Day 43).
‒ Changes from Screening in safety laboratory test and vital signs
assessment at Visit 3 (Day 43)
‒ Assessment of Adverse events (AEs) occurrence.
Exploratory endpoints:
‒ Percentage of subjects within each group with individual increases
greater than 0 letters in BCVA score based on ETDRS chart at Visit 3
(Day 43).
‒ Number of days between Baseline (Day 1) and administration of
rescue medication.
Early Efficacy:
‒ Change from Baseline within each cohort in BCVA score based on
ETDRS chart at Visit 1 and Visit 2 (after 14 and 29 days of treatment,
respectively).
‒ Change from Baseline within each cohort in the size of CNV (Flow
Area) observed with OCT angiography (OCTA) at Visit 1 and Visit 2 (after
14, and 29 days of treatment respectively) as determined by the central
reader.
‒ Changes from Baseline within each cohort in the following Optical
Coherence Tomography (SD-OCT)-observed biomarkers at Visit 1 and by the central reader:
o Presence and height/width of the largest cyst in central 1mm of
Intraretinal fluid (IRF)
o Presence and highest height/width of Subretinal fluid (SRF)
o Presence of drusenoid, vascular, or serous Pigment epithelial
detachments (PED)
o Central subfield thickness (CST)
o Disruption of external limiting membrane (ELM)
o Disruption of the ellipsoid zone (EZ)
Persistence:
‒ Change from End of Treatment within each cohort in BCVA score
based on ETDRS chart at Visit 4 / End of Study (after 14 days of
treatment discontinuation).
‒ Change from End of Treatment within each cohort in the size of CNV
(Flow Area) observed with OCT angiography (OCTA) at Visit 4 / End of
Study (after 14 days of treatment discontinuation) as determined by the
central reader.
‒ Changes from End of Treatment within each cohort in the following
Optical Coherence Tomography (SD-OCT)-observed biomarkers at Visit 4
/ End of Study (after 14 days of treatment discontinuation) as
determined by the central reader:
o Presence and height/width of the largest cyst in central 1mm of
Intraretinal fluid (IRF)
o Presence and highest height/width of Subretinal fluid (SRF)
o Presence of drusenoid, vascular, or serous Pigment epithelial
detachments (PED)
o Central subfield thickness (CST)
o Disruption of external limiting membrane (ELM)
o Disruption of the ellipsoid zone (EZ) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| 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 | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | Yes |
| 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 | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| 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 months | 10 |
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