E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory Wet Age-Related Macular Degeneration (wAMD) |
Refrakter, időskori, nedves típusú makula-degeneráció (wAMD) |
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E.1.1.1 | Medical condition in easily understood language |
Refractory Wet Age-Related Macular Degeneration (wAMD) |
Refrakter, időskori, nedves típusú makula-degeneráció (wAMD) |
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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 | LLT |
E.1.2 | Classification code | 10075568 |
E.1.2 | Term | Wet age-related macular degeneration |
E.1.2 | System Organ Class | 100000004853 |
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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 |
The primary objective of the study is to investigate the potential therapeutic effects of a 6-week, twice daily oral dosing regimen of ALK4290 on BCVA, as measured by ETDRS, in subjects with refractory wAMD following treatment with IVT anti-VEGF. |
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E.2.2 | Secondary objectives of the trial |
As a secondary objective, the study will assess the safety of the proposed dosing regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible for inclusion, all subjects must meet the following criteria: • Men and women with refractory active CNV secondary to AMD, diagnosed by a retinal specialist with all the following characteristics and ophthalmic inclusion criteria applied to the study eye: • Persistent exudation of SRF and IRF as documented by SD-OCT and absence of improvement in visual acuity following 3 consecutive (approximately 4 to 6 weeks apart) IVT anti-VEGF injections; subject must have received their last IVT anti-VEGF injection 30 to 90 days prior to the initial screening visit • Central subfield retinal thickness ≥ 250 microns on SD-OCT (exclusive of subretinal pigment epithelial fluid, inclusive of SRF) • Total lesion size not greater than 12 disc areas on FA • If present, subretinal hemorrhage must comprise < 50% of the total lesion area on FA • No subfoveal fibrosis or atrophy on FA • BCVA letter score, as measured by ETDRS in the study eye, between 70 and 24 letters, inclusive, at screening • Patients 50 years of age or older at screening visit 1 • Body mass index (BMI) between18 and ≤ 40 at screening visit 1 • Female subjects must not be pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in the study, she should inform her treating physician immediately • Signed informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions |
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E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion if any of the following criteria apply: • Treatment with IVT anti-VEGF therapy within 30 days preceding screening visit (Visit 1) in the study eye and/or planned concomitant IVT anti-VEGF treatment in the fellow eye during the study period • Previous participation in any studies of investigational drugs within 1 month preceding screening visit (Visit 1) • Any form of macular degeneration that is not age-related (e.g., Best’s disease, Stargardt’s disease, Sorsby’s disease, etc.) • Additional eye disease in the study eye that could compromise BCVA (i.e., uncontrolled glaucoma (intraocular pressure > 24) with visual field loss, clinically significant diabetic maculopathy, history of ischemic optic neuropathy or retinal vascular occlusion, vitreomacular traction, monocular vision, or genetic disorders such as retinitis pigmentosa; high myopia > 8 diopters) • Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with fundus photography/FA or SD-OCT • Intraocular surgery in the study eye within 3 months prior to screening • Aphakia or total absence of the posterior capsule (yttrium aluminum garnet (YAG) laser capsulotomy permitted, a minimum of 1 month prior to enrollment) in the study eye • Known allergy to fluorescein sodium for injection in FA • Current or planned use of medications known to be toxic to the retina, lens, or optic nerve (e.g.desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol) • Medical history or condition: - Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 8% - Myocardial infarction or stroke within 12 months of screening - Active bleeding disorder - Concomitant use of warfarin or anticoagulation therapy - Major surgery within 1 month of screening or planned within the study period - Hepatic impairment - Uncontrolled hypertension - Positive screening for Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV) • Planned concomitant use of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp) inhibitors or inducers during the study • Planned concomitant use of P-gp substrates that are narrow therapeutic index drugs (e.g., digoxin) • Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of first dose of study agent or known diseases which could require the use of systemic steroids within the study period • Use of intravitreal steroids: - Dexamethasone (Ozurdex) or triamcinolone within 6 months prior to screening - Flucinolon (Retisert or Iluvien) within 48 months prior to screening • Patients with a clinically relevant abnormal screening hematology, blood chemistry, or urinalysis, if the abnormality defines a significant disease as defined in other exclusion criteria (e.g., aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 2.0-fold the upper limit of normal at screening; total bilirubin or prothrombin time (INR) > 1.5 times the upper limit of normal at screening). Laboratory testing may be repeated once during the screening phase. • Patients with impaired renal function defined as calculated glomerular filtration rate (GFR) < 30 mL/min • Significant alcohol or drug abuse within past 2 years • Based on electrocardiogram (ECG) reading, patients with a risk of prolonged QT interval effects including: - A marked baseline prolongation of QTc (using Bazett’s formula: ≥ 430 ms in men and ≥ 450 ms in women) with confirmation on a repeat ECG) - A history of additional risk factors for Torsade de Pointes (TdP) (e.g., heart failure, hypokalemia, family, history of Long QT Syndrome, etc.) - The use of concomitant medications known to prolong the QT/QTc interval • Significant disease or other medical conditions (as determined by medical history, examination, and clinical investigations at screening) that may, in the opinion of the investigator, result in the any of the following: - Put the patient at risk because of participation in the study - Influence the results of the study - Cause concern regarding the patient’s ability to participate in the study • Patients with malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years; patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is mean changes in BCVA as measured by the ETDRS testing method.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoint is safety as assessed by incidence, seriousness, and severity of adverse events. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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
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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 | |
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 |