E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subfoveal Choroidal Neovascularization Associated with Age-Related Macular Degeneration |
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MedDRA Classification |
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 safety and efficacy of two doses (40 mg and 20mg) of Squalamine Lactate for Injection administered as intravenous infusions weekly for 4 weeks followed by maintenance doses every 4 weeks through week 104, compared with the safety and efficacy in the control group |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Must be considered reliable, willing and able to give informed consent. 2.Must be ≥50 years of age, male or female. 3.Must have subfoveal choroidal neovascularization (CNV) lesions associated with age-related macular degeneration (AMD) confirmed on fluorescein angiography in the study eye as predominantly classic, minimally classic or active occult. 4.Active occult lesion must have presumed evidence of disease progression, defined as: deterioration of best-corrected visual acuity (BCVA) by ≥1 line Snellen (≥5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol) within the past 3 months due to progression of CNV (not due to new onset CNV ), and one or more of the following — a.presence of subretinal/intraretinal blood; b.presence of subretinal/intraretinal fluid causing an increase in retinal thickness ≥250 microns confirmed by optical coherence tomography (OCT); c.growth of the lesion on fluorescein angiogram by ≥10% within the past 3 months. 5.The following additional criteria must also be met regardless of lesion type — a.lesion diameter ≤12 disc areas including all lesion components: CNV, blood, blocked fluorescence from lipid, fibrosis, pigment, or hypofluorescence from serous pigment epithelial detachment (PED); b.CNV under the geometric center of the foveal avascular zone; c.area of fibrosis <25% of the area of the lesion; d.area of subretinal blood <50% of the area of the lesion; 6.BCVA score must be between 64 to 24 letters on the ETDRS protocol 7. Subject must be an acceptable candidate for fundus photography and angiography — a.the eye must be able to be photographed resulting in images of sufficient quality such that the macular area can be assessed; b.pupil size must be ≥5 mm after dilatation for the study eye 8.Must have adequate organ function defined as a.marrow: white blood cells (WBC) ≥3000/mm3 (granulocytes ≥1500/mm3), platelets ≥100,000/mm3; hemoglobin (Hgb) ≥ 9 g/dL; b. hepatic: bilirubin ≤1.5 mg/dL, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤2x the upper limit of normal (ULN), and no hepatitis; c. renal: creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥60 mL/min; d. heart: adequately controlled ventricular ectopy, chronic atrial fibrillation with controlled ventricular response, or clinically stable rate controlled atrial fibrillation. 9. Women must be post-menopausal ≥1 year or surgically sterilized (negative serum pregnancy test required within 14 days prior to randomization); 10. Men must agree to use barrier contraception or abstinence throughout the study or be surgically sterilized. 11. BCVA or visualization of the macula must not be significantly impeded by cataracts or other media opacities.
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E.4 | Principal exclusion criteria |
1Previous laser photocoagulation therapy for “wet” AMD in the study eye (previous non-foveal photocoagulation and no more than one prior photodynamic therapy [PDT] with verteporfin are allowed). 2.PDT with verteporfin in the study eye within 3 months prior to entering the study. 3.Ocular surgery within the past 3 months for the study eye. 4.Refractive eye surgery within the past 3 months for the study eye 5.Glaucoma with visual field loss in the study eye (glaucoma and treatment in the fellow eye is acceptable). 6.Intraocular pressure ≥ 25 mmHg (off or on medication) in the study eye. 7.History of uveitis in the study eye. 8.Ongoing infection of any sort in either eye at Baseline. 9.Retinal or optic nerve disease that could independently affect visual acuity, including high axial myopia (>-8.00 diopters) or any diabetic retinopathy in the study eye. 10.Anterior segment and vitreous abnormalities that would preclude adequate observation of the fundus for photographs, fluorescein angiography and OCT in the study eye. 11.Use of investigational therapy within 30 days prior to Baseline. 12.Previous treatment with Squalamine Lactate for Injection. 13.Documented uncontrolled diabetes mellitus (best fasting plasma glucose >200 mg/dL in non-insulin dependent diabetes mellitus or >130 mg/dL in insulin-dependent diabetes mellitus). 14.Clinically uncontrolled malignancy (stable disease for 5 years is allowed). 15.Acute atrial fibrillation; recent myocardial infarction (<6 months); unstable angina; poorly controlled congestive heart failure; greater than first degree atrioventricular block; and clinically significant atrial or ventricular arrhythmias. 16.A systemic or mental health condition that the investigator considers to be a reason for exclusion. 17.Allergy to fluorescein dye, ICG dye, or iodine. 18.Use of systemic or topical medications known to be toxic to the retina, lens, or optic nerve, eg, deferoxamine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, and ethambutol (see Study Reference Manual for complete list). 19.Use of intravitreal or periocular injectable agents, including steroids, in the study eye. 20.Use of high dose systemic steroids (>10mg prednisone or equivalent /day) within the past 6 months. 21.Use of topical steroids in the study eye within the past 1 month. 22.Use of any antiangiogenic compound locally or systemically (eg, thalidomide, bevacizumab (Avastin®) - see Study Reference Manual for complete list).
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E.5 End points |
E.5.1 | Primary end point(s) |
Loss in BCVA of ≥ 15 letters (ETDRS) at 52 weeks in the study eye compared to baseline.
Secondary endpoints are as follows: 1. Loss in BCVA of ≥15 letters (ETDRS) at 104 weeks in the study eye compared to baseline. 2. Gain in BCVA of ≥15 letters (ETDRS) at 52 and 104 weeks in the study eye compared to baseline. 3. Loss in BCVA of ≥15 letters (ETDRS) at 52 and 104 weeks in the fellow eye compared to baseline in the subgroup of subjects whose fellow eye is affected with “wet” AMD (ie, subfoveal CNV lesions due to AMD confirmed on fluorescein angiography as predominantly classic, minimally classic or active occult). 4. Gain in BCVA of ≥15 letters (ETDRS) at 52 and 104 weeks in the fellow eye compared to baseline in the subgroup of subjects whose fellow eye is affected with wet AMD. 5. Loss in binocular visual acuity of ≥15 letters at 52 and 104 weeks compared to baseline, using a modified ETDRS protocol. 6. Gain in binocular visual acuity of ≥15 letters at 52 and 104 weeks compared to baseline, using a modified ETDRS protocol. 7. Change in visual functioning and health-related quality of life at 52 and 104 weeks compared to baseline, as measured by the National Eye Institute Visual Functioning Questionnaire-25 (VFQ-25). 8. Change in retinal thickness (Bruch’s membrane to inner limiting membrane [ILM]) in the study eye at 52 and 104 weeks compared to baseline, as measured by OCT, in a subset of subjects. 9. Change in area of CNV in the study eye at 52 and 104 weeks compared to baseline, as measured by fluorescein angiography. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Active product is diluted in 5% Dextrose Injection, USP; control is Dextrose Injection, USP |
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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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |