| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Neovascular (wet) Age-related Macular Degeneration |
| Neovaszkuláris (nedves), életkorral összefüggő makuladegeneráció |
|
| E.1.1.1 | Medical condition in easily understood language |
| Age-related macular degeneration (AMD) is the leading cause of irreversible blindness and visual impairment in elderly population |
|
| 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 | 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 |
|
| 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 demonstrate the equivalent efficacy of AVT06 to Eylea in subjects with neovascular (wet) age-related macular degeneration (AMD) |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of AVT06 compared with Eylea in subjects with neovascular (wet) AMD.
• To evaluate the safety and tolerability of AVT06 compared with Eylea.
• To assess immunogenicity of AVT06 compared with Eylea.
• To evaluate the systemic PK of AVT06 and Eylea in a subset of subjects. |
|
| 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 |
| Details of the pharmacokinetics (PK) sub-study is included in the study protocol. The primary objective of the sub-study is to evaluate the systemic pharmacokinetics (PK) of AVT06 and Eylea in a subset of subjects. |
|
| E.3 | Principal inclusion criteria |
Age
• Subject must be ≥50 years of age, at the time of signing the informed consent.
Study Eye
• Subjects must be diagnosed with neovascular (wet) AMD in the study eye.
• Subjects must have active, treatment naïve, subfoveal CNV lesions secondary to neovascular (wet) AMD, including juxtafoveal lesions with foveal involvement (demonstrated by leakage on FA and/or intraretinal fluid or subretinal fluid on SD-OCT) in the study eye at screening.
• Subjects with total lesion area ≤9.0 Disc Areas in size (including blood, scars [not involving the center of the fovea], and neovascularization) in the study eye at screening.
• Subjects with active CNV area must occupy at least 50% of total lesion in the study eye.
• Subjects with BCVA of 20/40 to 20/200 (between 73 and 34 letters inclusive), in the study eye as assessed by ETDRS letter score at screening and on Day 1 prior to randomization.
• Presence of intra and/or subretinal fluid as identified in the center subfield by SD-OCT attributable to active CNV in the study eye at screening.
• Subjects with central retinal thickness of ≥300 µm in the study eye as determined by SD OCT at screening.
Sex
Male or female
a) Male subjects:
• A male subject must agree to use contraception as detailed in Appendix 6 of this protocol during the treatment period and for at least 3 months after the last intravitreal injection of study treatment and refrain from donating sperm during this period.
b) Female subjects:
• A female subject is eligible to participate if she is not pregnant (see Appendix 6), not breastfeeding, not intending to become pregnant during the treatment period and for at least 3 months after the last intravitreal injection of study treatment, and at least 1 of the following conditions applies:
i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 6.
OR
ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 during the treatment period and for at least 3 months after the last intravitreal injection of study treatment.
Informed Consent
Capable of giving signed informed consent as described in Appendix 2, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
|
|
| E.4 | Principal exclusion criteria |
Study Eye
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
History of retinal detachment in the study eye.
Presence of RPE tears involving the macula in the study eye.
History of any vitreous hemorrhage within 4 weeks before randomization in the study eye.
Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye.
Uncontrolled ocular hypertension (defined as IOP ≥25 mmHg despite treatment with anti glaucoma medication) at screening and randomization visits in the study eye.
Any history of macular hole in the study eye.
Any concurrent macular abnormality other than wet AMD which could affect central vision or the efficacy of the study treatment in the study eye.
Aphakia or absence of the posterior capsule (unless it occurred as a result of a posterior capsulotomy with neodymium doped yttrium aluminium garnet [YAG] laser following cataract surgery with intraocular lens implantation) in the study eye.
Significant media opacities, including cataract or inadequate pupil dilatation, which might interfere with visual acuity or assessment of safety in the study eye.
History of corneal transplant, corneal dystrophy, or corneal ectasia (such as either keratoconus or keratoglobus) in the study eye.
Subjects with previous ocular (intraocular and peribulbar) corticosteroids injection/implant within 1 year in the study eye prior to randomization.
Topical ocular corticosteroids for 30 or more consecutive days within 90 days prior to randomization in the study eye.
Previous therapeutic radiation in the region of the study eye.
Any prior ocular treatment, including surgery or another investigational product for neovascular AMD (including anti-VEGF therapy), in the study eye, except dietary supplements or vitamins.
Concurrent ocular condition which, in the opinion of the Investigator, could require medical or surgical intervention during the study period and/or confound the interpretation of the study results.
Either Eye
History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular AMD.
Active or suspected ocular or periocular infection, within 2 weeks before randomization.
Active scleritis or episcleritis or presence of scleromalacia.
Fellow Eye
Any ocular treatment, including surgery or another investigational product for neovascular AMD (including anti-VEGF treatment), in the fellow eye, within 6 months before randomization, except dietary supplements or vitamins.
Subjects with BCVA of 20/200 or less (34 letters or less) in the fellow eye as assessed by ETDRS letter score at screening and on Day 1 prior to randomization.
Subjects with any diagnosis and/or signs of neovascular AMD requiring intravitreal anti VEGF in the fellow eye, or in the opinion of the Investigator, are expected to require such treatments before the evaluation of the primary efficacy endpoint (ie, Week 8) and completion of PK sampling (ie, Week 12) for the subjects in the PK sub-study.
Other
Any prior systemic treatment with anti-VEGF therapy.
History of hypersensitivity or anaphylaxis to study treatments (including any excipient), and/or history of hypersensitivity to fluorescein sodium for injection in angiography or to any other compound used for the study procedures.
Prior treatment with any investigational drugs within 30 days or 5 half-lives (whichever is longer) of the previous investigational treatment before initiation of the study treatment or concomitant enrollment in any other clinical study involving an investigational study treatment.
Acute coronary event or stroke within 6 months before randomization.
Uncontrolled diabetes mellitus with glycosylated hemoglobin (HbA1c) >8%.
Cardiovascular disease including uncontrolled hypertension, uncontrolled heart failure, history of coronary event or stoke, or clinically significant electrocardiogram (ECG) abnormality, including subjects with QT interval corrected using Fridericia’s formula [QTcF] >480 ms at screening, confirmed by repeat assessment. Uncontrolled hypertension is defined in Appendix 10.
Any condition that, in the Investigator´s opinion, can interfere with full participation in the study, including administration of the study treatment and attending required visits; can pose a significant risk to the participant, or interfere with interpretation of study data.
Malignancy diagnosed within 5 years except treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
Subjects not suitable for participation, whatever the reason, as judged by the Investigator, including medical or psychiatric conditions, or participants potentially at risk of noncompliance to study procedures.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Change from baseline to Week 8 in BCVA as measured by ETDRS letter score. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From baseline to Week 8 in BCVA as measured by ETDRS letter score. |
|
| E.5.2 | Secondary end point(s) |
• Change from baseline in BCVA as assessed by ETDRS letter score at Week 4, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Gain of ≥5, 10, 15 letter score in BCVA from baseline to Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Loss of ≥5, 10, 15 letter score in BCVA from baseline to Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Change from baseline in CST as assessed by SD OCT at Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Change from baseline in CNV area as assessed by FA and color FP at Week 8, Week 24, and Week 52.
• Incidence of ocular and non-ocular TEAEs, AESIs, and SAEs.
• Evaluation of ophthalmic parameters (IOP, biomicroscopy, and indirect ophthalmoscopy).
• Evaluation of routine safety parameters, including safety laboratory, 12-lead ECG results, vital signs, and physical examination.
• Proportion of subjects testing positive for ADAs, including NAb from baseline to Week 8, Week 16, Week 24, and Week 52.
• Evaluate systemic PK profile of free and bound aflibercept from baseline (Day 1 predose) to Day 1 (1 to 4 hours postdose), Day 2, Day 3, Week 4, Week 8, and Week 12.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Change from baseline in BCVA as assessed by ETDRS letter score at Week 4, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Gain of ≥5, 10, 15 letter score in BCVA from baseline to Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Loss of ≥5, 10, 15 letter score in BCVA from baseline to Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Change from baseline in CST as assessed by SD OCT at Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, and Week 52.
• Change from baseline in CNV area as assessed by FA and color FP at Week 8, Week 24, and Week 52.
• Proportion of subjects testing positive for ADAs, including NAb from baseline to Week 8, Week 16, Week 24, and Week 52.
For full list please see the Protocol. |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| 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 | 9 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 42 |
| 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 |
| Argentina |
| Brazil |
| India |
| Japan |
| Georgia |
| Russian Federation |
| Ukraine |
| Bulgaria |
| Czechia |
| Hungary |
| Latvia |
| Poland |
| Slovakia |
|
| 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
|
|
| 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
| 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 | 9 |
Print
