E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular age-related macular degeneration (wet AMD) |
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E.1.1.1 | Medical condition in easily understood language |
Chronic eye disease that causes blurred vision or a blind spot in one´s visual field caused by abnormal blood vessels leaking fluid or blood into the part of the retina responsible for central vision |
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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 | SOC |
E.1.2 | Classification code | 10015919 |
E.1.2 | Term | Eye disorders |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 | 10071129 |
E.1.2 | Term | Neovascular age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067791 |
E.1.2 | Term | Wet macular degeneration |
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 |
Determine the efficacy of two different doses of intravitreal OPT-302 when administered in combination with ranibizumab in participants with wet AMD |
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E.2.2 | Secondary objectives of the trial |
* Determine the proportion of participants gaining 15 or more ETDRS BCVA letters from Baseline to Week 24; * Determine the area under the ETDRS BCVA over time curve; * Determine the change in central subfield thickness (CST) on spectral domain optical coherence tomography (SD-OCT) from Baseline to Week 24; * Determine the change in sub-retinal fluid on SD-OCT from Baseline to Week 24; * Determine the presence or absence of intra-retinal fluid on SD-OCT from Baseline to Week 24; * Determine the proportion of participants losing 15 or more letters (on ETDRS BCVA chart) from Baseline to the Week 24 Visit; * Determine the safety of OPT-302 in combination with ranibizumab; * Determine the pharmacokinetic parameters of OPT-302; * Determine the incidence of anti-OPT-302 antibody (ADA) formation. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
* Title: Pharmacokinetic Sub-Study * Version: 2.0 * Date: 2017-11-21 * Objective: To gather further pharmacokinetic data for OPT-302 to build on the population PK (PopPK) model developed using the PK data from study OPT-302-1001 |
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E.3 | Principal inclusion criteria |
STUDY EYE 1. Active subfoveal choroidal neovascular (CNV) lesion or juxtafoveal CNV lesion (1-199 μm from the fovea) with subfoveal involvement (demonstrated by leakage on fluorescein angiography (FA) and/or intra-retinal or sub-retinal fluid on spectral-domain optical coherence tomography [SD-OCT]) secondary to age-related macular degeneration (AMD). Active CNV as measured on FA must constitute at least 50% of the lesion area, with a total lesion size of ≤ 30.5 mm2. The lesion may contain classic and/or occult CNV, but any occult CNV present must measure < 10 mm2 on the FA. The characteristics of each lesion must be confirmed by the Independent Reading Centre. 2. A best corrected (ETDRS) visual acuity (BCVA) score between 60 and 25 (inclusive) letters (Snellen equivalent of 20/63 (feet) or 6/21 (metres) and 20/320 (feet) or 6/96 (metres) respectively).
GENERAL 1. Willing and able to provide written informed consent. 2. Male or female participants at least 50 years of age. 3. Able to understand and willing to comply with study protocol procedures and restrictions. 4. If female and of child-bearing potential: Pregnancy test at Screening is negative, and agrees to use a highly effective method of contraceptive for the duration of the study and for at least 3 months following the last dose of study medication. |
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E.4 | Principal exclusion criteria |
STUDY EYE 1. Any previous treatment for wet AMD, including anti-VEGF-A therapy, photodynamic therapy, thermal laser, external beam radiation, steroids or other AMD therapy in the Study Eye. Oral supplements of vitamins and minerals are permitted. 2. Clinically significant ocular disorders (other than wet AMD), which may, in the Investigator’s opinion, interfere with assessment of visual acuity, assessment of safety, OCT, fluorescein angiography or fundus photography; 3. Haemorrhage measuring more than 50% of total lesion area; 4. Fibrosis involving either the fovea centre or measuring more than 25% of the total lesion area and/or juxtafoveal or sub-foveal geographic atrophy. 5. Choroidal neovascularisation due to causes other than AMD, including presumed ocular histoplasmosis syndrome, angioid streaks, multifocal choroiditis, choroidal rupture, and pathological myopia. Participants with retinal angiomatous proliferation (RAP) or idiopathic polypoidal choroidal vasculopathy (IPCV) are not excluded. 6. Cloudy ocular media, or inadequate pupillary dilatation, so as to prevent collection of fundus photographs and/or fluorescein angiograms of sufficient quality to be analysed by the Independent Reading Centre. 7. Presence of intraocular inflammation (≥ trace cell or flare), significant epiretinal membrane or vitreomacular traction, macular hole or vitreous haemorrhage. 8. Aphakia or absence of the posterior capsule. Absence of an intact posterior capsule is permitted if it occurred as a result of a YAG laser posterior capsulotomy in association with prior posterior chamber intraocular lens implant. 9. History of idiopathic or autoimmune-associated uveitis. 10. Any current ocular or periocular infection (participants may be re-screened once the infection has resolved or responded fully to treatment). 11. Intraocular pressure of greater than 25 mmHg (including participants with glaucoma or ocular hypertension who are stabilised on therapy). 12. Myopia, or known former myopia, with a spherical equivalent of greater than 8 dioptres. 13. Intraocular surgery within 6 months prior to screening, except for cataract surgery that is excluded within 3 months of Screening. 14. History of any of the following conditions or procedures: Rhegmatogenous retinal detachment, filtering surgery (e.g. trabeculectomy), glaucoma drainage device, or corneal transplant. 15. Prior pars plana vitrectomy. 16. Presence of an intravitreal device. 17. Retinopathy from diabetes, sickle cell disease or other cause.
NON-STUDY EYE 1. History of idiopathic, autoimmune-associated, or infectious uveitis.
GENERAL 1. Poorly controlled diabetes mellitus (defined as HbA1c > 7.0%). 2. Administration of systemic steroids within 3 months of screening. 3. Symptoms of heart failure leading to marked limitation on physical activity, or inability to perform any physical activity without discomfort. 4. Unstable angina, myocardial infarction or coronary artery revascularisation within 6 months of screening. 5. Ventricular tachyarrhythmia requiring ongoing treatment. 6. Vascular stenting within 6 months of screening. 7. Cerebrovascular event, including transient ischaemic attack (TIA), within 6 months of screening. 8. Diastolic blood pressure > 100 mmHg at screening. Subjects with a history of controlled hypertension on medication may have their blood pressure measured at a second visit, and will qualify if diastolic blood pressure ≤ 100 mmHg on repeat testing. 9. Renal failure requiring dialysis or transplant. 10. ALT or AST ≥ 2 x upper limit of normal (ULN), or total bilirubin ≥ 1.5 x ULN (unless due to genetically confirmed Gilbert’s disease). 11. Any major surgical procedure (defined as any surgery requiring general anaesthesia) within one month of trial entry, or planned during the study period. 12. Active systemic infection (participants may be re-screened once the infection has resolved or responded fully to treatment). 13. Malignancy within 5 years of screening, with the exception of carcinoma in situ, non-melanoma skin cancers and prostate cancer not requiring treatment or on stable (> 6 months) treatment with hormone therapy. 14. Known serious allergies to the fluorescein dye used in angiography (mild allergy amenable to treatment is allowable), or hypersensitivity to any of the listed excipients in the OPT-302 formulation or components of the ranibizumab formulation. 15. Pregnant, within 3 months after the end of pregnancy, planning to become pregnant, or lactating. 16. Previous administration of anti-VEGF-A therapies via any route and for any indication, except by intravitreal injection in the non-Study Eye 17. Administration of an investigational drug or ocular device within 30 days of screening, or 5 half-lives, whichever is the longer, or any prior treatment with OPT-302. 18. Any social or medical condition that, in the Investigator’s opinion, would preclude enrolment into the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from Baseline in Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) letters to Week 24 (Visit 8) |
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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 proportion of participants gaining 15 or more ETDRS BCVA letters from Baseline to the Week 24 Visit; * Area under the ETDRS BCVA-over-time curve; * Change in CST on SD-OCT from Baseline to Week 24; * Change in sub-retinal fluid on SD-OCT from Baseline to Week 24; * Presence or absence of intra-retinal fluid determined by the presence or absence of intra-retinal cysts on SD-OCT from Baseline to Week 24; * Proportion of participants losing 15 or more letters (on ETDRS BCVA chart) from Baseline to the Week 24 Visit; * Incidence of ocular and non-ocular adverse events (AEs); * OPT-302 pharmacokinetic parameters; * Participant incidence of ADA formation. |
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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 | Yes |
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 |
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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 | 58 |
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 |
Czech Republic |
France |
Hungary |
Israel |
Italy |
Latvia |
Poland |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |