E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular Age-related Macular Degeneration |
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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 | 27.0 |
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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of ABP 938 compared to aflibercept. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and immunogenicity of ABP 938 compared to aflibercept |
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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 |
Pharmacokinetic Substudy Approximately 32 subjects will be consented and enrolled into a PK substudy. These subjects will have a PK sample collected predose (within 60 minutes before day 1 dose) and postdose (approximately 24 hours after day 1 dose), with an allowable window 6 hours to +24 hours (ie, 18 hours to 48 hours after day 1 dose) and postdose at week 8 (approximately 24 hours after week 8 dose), with an allowable time window of 6 hours to +24 hours (ie, 18 hours to 48 hours postdose). |
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E.3 | Principal inclusion criteria |
1. Subjects or their legally authorized representative must sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form (ICF) before any study-specific procedures 2. Men or women ≥ 50 years old 3. Subjects must be diagnosed with neovascular (wet) AMD in the study eye (confirmed by central imaging vendor before randomization) 4. Active, treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD including juxtafoveal lesions that affect the fovea as confirmed with SD-OCT, FA and/or FP in the study eye (confirmed by central imaging vendor before randomization) 5. BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing 6. Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye (confirmed by central imaging vendor before randomization) 7. Central retinal thickness (CRT) of ≥ 300 µm in the study eye as measured by the machine, calculated average thickness in the ETDRS central 1 mm subfield (CST) by SD-OCT at screening (confirmed by central imaging vendor before randomization)
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E.4 | Principal exclusion criteria |
1. Total lesion size > 12 disc areas (30.5 mm2, including blood, scars, and neovascularization) in the study eye (confirmed by central imaging vendor before randomization) 2. Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye (confirmed by central imaging vendor before randomization) 3. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye (confirmed by central imaging vendor before randomization) 4. Presence of retinal pigment epithelium tears or rips involving the macula in the study eye (confirmed by central imaging vendor before randomization) 5. History of any vitreous hemorrhage within 4 weeks before randomization in the study eye 6. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye (confirmed by central imaging vendor before randomization with the exception of the refractive error and axial length which is to be assessed by the investigator) 7. Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye 8. History of retinal detachment in the study eye 9. Any history of macular hole of stage 2 and above in the study eye 10. Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane (confirmed by central imaging vendor before randomization) 11. Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection 12. Prior trabeculectomy or other filtration surgery in the study eye 13. Uncontrolled glaucoma (defined as intraocular pressure [IOP] ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye 14. Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye 15. Previous therapeutic radiation in the region of the study eye 16. History of corneal transplant or corneal dystrophy in the study eye 17. Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye 18. Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety 19. History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD (confirmed by central imaging vendor before randomization) 20. Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization 21. Active scleritis or episcleritis or presence of scleromalacia 22. Active extraocular infection or history of extraocular infections as follows: a. any active infection for which systemic anti-infectives were used within 4 weeks before randomization b. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject 23. Acute coronary event or stroke within 3 months before randomization 24. Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease 25. Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 26. Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins 27. Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins 28. Prior systemic anti-VEGF treatment as follows: a. Investigational or approved anti-VEGF therapy systemically within 3 months before randomization b. Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in best corrected visual acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at week 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) |
- Proportion of subjects who maintained vision at week 52, where a subject was classified as maintaining vision if he/she lost fewer than 15 letters in ETDRS letter score compared to baseline - Change from baseline in BCVA as measured by ETDRS letter score over the study duration - Proportion of subjects who gained at least 10 letters of vision at week 8 and proportion of subjects who gained at least 15 letters of vision at week 52 as compared to baseline - Change from baseline in choroidal neovascularization (CNV) area as measured by fluorescein angiography (FA) and central subfield thickness (CST) and spectral domain optical coherence tomography (SD OCT) over the study duration - Treatment-emergent adverse events, adverse events of interest (EOIs), and serious adverse events - Incidence of antidrug antibodies (ADA) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
throughout the duration of the study |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 59 |
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 |
Hong Kong |
Canada |
Israel |
Japan |
Korea, Republic of |
Mexico |
Serbia |
United States |
Czechia |
Estonia |
Germany |
Hungary |
Italy |
Latvia |
Poland |
Slovakia |
Spain |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 18 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 18 |