E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular (Wet) Age-related Macular Degeneration |
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E.1.1.1 | Medical condition in easily understood language |
Neovascular (Wet) Age-related Macular Degeneration |
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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 | 20.1 |
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.1.2 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA) from Day 1 to Year 1. Year 1 is defined as the mean of the Week 48 and 52 measurements. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg from Day 1 to Week 96 by assessing visual and anatomical parameters.
•To evaluate the proportion of subjects maintained on a Q12W, Q16W, or Q20W dosing regimen of KSI-301 over the duration of the first 52 weeks.
•To evaluate the safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg.
•To assess the systemic pharmacokinetics and immunogenicity of KSI-301. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD, including subfoveal, juxtafoveal and extrafoveal lesions or retinal angiomatous proliferation (RAP) lesions with a CNV component that affect the central subfield as evidenced by FA or OCT in the Study Eye at Screening.
2.The CNV area in the Study Eye must be at least 50% of total lesion size at Screening.
3.A lesion area <30 mm2 (12 disc areas) of any CNV lesion subtype in the Study Eye.
4.Intra and/or subretinal fluid and/or SHRM (subretinal hyperreflective material) affecting the central subfield of the Study Eye on OCT at Screening.
5.BCVA ETDRS score between 80 and 25 letters (20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye at Screening and reconfirmed at Day 1.
6.Decrease in vision in the Study Eye determined by the Investigator to be primarily the result of wet AMD.
7.Capable of understanding the informed consent, provides signed and
dated informed consent, and agrees to comply with protocol
requirements.
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E.4 | Principal exclusion criteria |
1.BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular).
2.Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
3.CNV secondary to other causes in the Study Eye, including pathologic myopia, angioid streaks, prior trauma, ocular histoplasmosis, or others.
4.Any history of macular pathology unrelated to AMD but affecting vision or contributing to subretinal or intraretinal fluid, such as central serous chorioretinopathy.
5.Fibrosis or atrophy of >50% of the lesion size and/or involving the foveal center of the Study Eye at Screening
6.Subretinal blood affecting the foveal center of the Study Eye and/or more than 50% of the lesion size at Screening.
7.Any approved or investigational treatment for neovascular AMD (other than oral vitamin supplements) in the Study Eye at any time.
8.Prior macular laser (e.g., thermal laser or photodynamic therapy laser) in the Study Eye. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study will be the mean change in BCVA from Day 1 to Year 1, comparing subjects receiving KSI-301 to aflibercept at a non-inferiority margin of 4 letters. Year 1 is defined as the mean BCVA at Weeks 48 and 52. |
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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) |
At Year 1:
•Proportion of subjects on a Q12W, Q16W or Q20W dosing regimen of KSI-301 at 52 weeks
•Proportion of subjects who gain ≥ 5, ≥10 and ≥15 letters from baseline over time
•Proportion of subjects who lose ≥ 5, ≥10 and ≥15 letters from baseline over time
•Mean change from baseline in BCVA from baseline to Week 12, Week 16, and over time
•Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time
•Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time
•Mean change in OCT CST from baseline to Week 12, Week 16, and over time
•Mean change in OCT intraretinal fluid volume from baseline to Week 12, Week 16, and over time
•Mean change in OCT subretinal fluid volume from baseline to Week 12, Week 16, and over time
•Proportion of subjects without intraretinal fluid on OCT from baseline to Week 12, Week 16 and over time
•Proportion of subjects without subretinal fluid on OCT from baseline to Week 12, Week 16 and over time
•Proportion of subjects without pigment epithelial detachments on OCT from baseline over time
•Mean change in CNV total lesion area on FA from baseline at Year 1
•Mean chance in area of leakage on FA from baseline at Year 1
•Number of study drug injections received in the KSI-301 and aflibercept groups through
Year 1
•For the KSI-301 group, the predictability of being on Q12W, Q16W, or Q20W dosing at the end of Year 1 on the basis of the first set of Disease Activity Assessments (at Weeks 20 and 24).
At Year 2:
•Proportion of subjects who gain ≥ 5, ≥10 and ≥15 letters from baseline over time
•Proportion of subjects who lose ≥ 5, ≥10 and ≥15 letters from baseline over time
•Mean change from baseline in BCVA from baseline over time
•Proportion of subjects with BCVA Snellen equivalent of 20/40 or better from baseline over time
•Proportion of subjects with BCVA Snellen equivalent of 20/200 or worse from baseline over time
•Mean change in OCT CST from baseline over time
•Mean change in OCT intraretinal fluid volume from baseline to Week 12, Week 16, and over time
•Mean change in OCT subretinal fluid volume from baseline to Week 12, Week 16, and over time
•Proportion of subjects without intraretinal fluid on OCT from baseline over time
•Proportion of subjects without subretinal fluid on OCT from baseline over time
•Proportion of subjects without pigment epithelial detachments on OCT from baseline over time
•Mean change in CNV total lesion area on FA from baseline at Year 2
•Mean chance in area of leakage on FA from baseline at Year 2
For BCVA and OCT, Year 1 is defined as the average measurement at Weeks 48 and 52 and Year 2 is defined as the average measurement at Weeks 92 and 96.
A full list of secondary endpoints, including the delineation of key versus additional secondary endpoints, will be outlined in the SAP.
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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 | 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 | 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 | 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) | 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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
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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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The end of the study according to the protocol is defined as the last
follow-up visit of the last subject enrolled or a Sponsor decision to
terminate the study, whichever comes first.
Study data may be collected beyond the end of the study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |