E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular (Wet) Age-related Macular Degeneration (wAMD) |
|
E.1.1.1 | Medical condition in easily understood language |
Neovascular (Wet) Age-related Macular Degeneration (wAMD) |
|
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 |
|
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064930 |
E.1.2 | Term | Age-related macular degeneration |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075568 |
E.1.2 | Term | Wet 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 that KSI-301 5 mg is non-inferior to aflibercept 2 mg, with respect to the change in best
corrected visual acuity (BCVA) from Day 1 to Week 40. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg over the study duration by assessing visual parameters.
To evaluate the efficacy of KSI-301 5 mg compared to aflibercept 2 mg over the study duration by assessing anatomical parameters.
To evaluate the safety and tolerability of KSI-301 5 mg compared to aflibercept 2 mg.
To assess the systemic pharmacokinetics (exposure) and immunogenicity of KSI-301. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
5.1.1 Ocular Inclusion Criteria
1. Active, treatment-naïve choroidal neovascularization (CNV) secondary to AMD, including
subfoveal, juxtafoveal, and extrafoveal lesions, or retinal angiomatous proliferations (RAP)
lesions with a CNV component that affects 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. The lesion area in the Study Eye must be <30 mm2 (12-disc areas) and can include any CNV
lesion subtype.
4. Intra- and/or subretinal fluid and/or subretinal hyperreflective material (SHRM) affecting the
central subfield of the Study Eye on OCT at Screening.
5. BCVA ETDRS score between 83 and 25 letters, 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 wAMD.
In cases where both eyes are eligible, the eye with the worse BCVA at the Screening Visit will
be selected as the Study Eye. If both eyes are eligible and have the same BCVA, the decision of
which eye to select as the Study Eye will be made by the Investigator. Only one eye per participant can participate in the study.
5.1.2 General Inclusion Criteria
7. Capable of giving signed informed consent as described in Appendix 1, which includes
compliance with the protocols and restrictions listed in the informed consent form (ICF) and
in this protocol.
8. Male or female ≥50 years of age.
9. For women of childbearing potential: agreement to remain as abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per
year during the treatment period and for at least 90 days after the last dose of study drug.
Women of childbearing potential must have a negative urine pregnancy test result within 28
days prior to Day 1. If the urine pregnancy test is positive, it must be confirmed with a serum
pregnancy test.
A woman is considered of childbearing potential if she is postmenarcheal, has not
reached a postmenopausal state (≥12 months of amenorrhea with no identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus). The definition of childbearing potential may be adapted for
alignment with local guidelines or requirements.
b. Examples of contraceptive methods with a failure rate of <1% per year include
bilateral tubal ligation, male sterilization, established, proper use of hormonal
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices and
copper intrauterine devices.
c. Contraception methods that do not result in a failure rate of <1% per year such as cap,
diaphragm, or sponge with spermicide, or male or female condom with or without
spermicide, are not acceptable.
d. The reliability of sexual abstinence should be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the participant. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
withdrawal are not acceptable methods of contraception.
10. For men: agreement to remain abstinent or use contraceptive measures and agreement to
refrain from donating sperm, as defined below:
a. With female partners of childbearing potential, men must remain abstinent or use a
condom plus an additional contraceptive method that together result in a failure rate
of <1% per year during the treatment period and for at least 30 days plus 90 days (a
spermatogenesis cycle) after the last dose of study drug. Men must refrain from
donating sperm during this same time period.
11. Ability and willingness to undertake all the scheduled visits and assessments. |
|
E.4 | Principal exclusion criteria |
5.2.1 Ocular Exclusion Criteria
Where applicable exclusion criteria will be confirmed or assessed by the independent, masked
image Reading Center.
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 Screening
or on 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. Retinal pigment epithelium tear or rip in the Study Eye at Screening or on Day 1.
8. Any approved or investigational treatment for neovascular AMD (other than oral vitamin
supplements) in the Study Eye at any time.
9. Prior macular laser (e.g., thermal laser or photodynamic therapy laser) in the Study Eye.
10. Any history or evidence of a concurrent ocular condition present in the Study Eye, that in the
opinion of the Investigator could require either medical or surgical intervention or affect
macular edema or alter visual acuity during the study (e.g., vitreomacular traction, epiretinal
membrane).
11. History of cataract surgery and/or minimally invasive glaucoma surgery (MIGS) in the Study
Eye within 2 months of screening.
12. History of Yttrium-Aluminum Garnet (YAG) laser capsulotomy in the Study Eye within 2
months of screening.
13. Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with
antiglaucoma medication) in the Study Eye.
14. History of glaucoma-filtering surgery (trabeculectomy or tube shunt) in the Study Eye.
15. History of retinal detachment or treatment or surgery for retinal detachment in the Study Eye.
16. History of uveitis in either eye.
17. Significant media opacities, including cataract, in the Study Eye that might interfere with
visual acuity, assessment of safety, OCT or fundus photography.
18. Cataract in the Study Eye that in the judgment of the Investigator is expected to require
surgical extraction within 12 months of screening.
19. Aphakia in the Study Eye.
20. Prior vitrectomy in the Study Eye.
21. Prior intraocular or periocular steroids in the Study Eye.
22. Current vitreous hemorrhage or history of vitreous hemorrhage in the Study Eye within 3
months of Screening.
23. History of corneal transplant in the Study Eye.
5.2.2 General Exclusion Criteria
1. Women who are pregnant or lactating or intending to become pregnant during the study
2. Recent history (within the 6 months prior to screening) of myocardial infarction, stroke,
transient ischemic attack, acute congestive heart failure or any acute coronary event.
3. History of a medical condition that, in the judgment of the Investigator, would preclude
scheduled study visits, completion of the study, or a safe administration of investigational
product.
4. History of hypersensitivity to any component of KSI-301, aflibercept, ophthalmic dye
(fluorescein), dilating drops, or any of the anesthetic or antimicrobial preparations used
during the study, as assessed by the Investigator.
5. Participation in an investigational study within 30 days prior to the screening visit that
involved treatment with any investigational drug (excluding vitamins and minerals) or
device, except for non-therapeutic ophthalmic imaging devices.
24. Active cancer within the 12 months prior to Screening except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin cancer, and prostate cancer with a
Gleason score of <6 and stable prostate-specific antigen for >12 months.
25. Treatment with systemic anti-VEGF therapeutics within 90 days prior to Screening.
26. Uncontrolled blood pressure defined as a systolic value ≥180 mmHg or diastolic value ≥100
mmHg while at rest at Screening or on Day 1.
• If a participant’s initial blood pressure measurement exceeds these values, up to
two additional readings may be taken later the same day or on a different day
during the screening period. If a participant’s blood pressure is controlled by
antihypertensive medications, the participant must be on a stable medication
regimen continuously for 21 days prior to Day 1. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean change in BCVA from baseline (Day 1) to
Week 40, in Early Treatment Diabetic Retinopathy
Study (ETDRS) Letters. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be assessed using ETDRS data collected up to Week 40. |
|
E.5.2 | Secondary end point(s) |
• Mean change in BCVA (ETDRS Letters) from baseline (Day 1) by visit over time.
• Proportion of participants who gain ≥5, ≥10 and ≥15 ETDRS letters from baseline
(Day 1) by visit over time.
• Proportion of participants who lose ≥5, ≥10 and ≥15 ETDRS letters from baseline
(Day 1) by visit over time.
• Proportion of participants with BCVA Snellen equivalent of 20/40 or better from baseline
(Day 1) over time.
• Proportion of participants with BCVA Snellen equivalent of 20/200 or worse from
baseline (Day 1) over time.
• Mean change in OCT CST from baseline (Day 1) to Week 40 and over time.
• Incidence of ocular and systemic AEs up to Week 44.
• Systemic anti-drug antibody status over time (in the ADA-evaluable population).
• Systemic pharmacokinetic profile (i.e., systemic exposure) over time (in the PK-evaluable population).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary endpoints will be assessed at Week 40 (for efficacy) or Week 44 (for safety) |
|
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) | 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 | 26 |
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 |
United States |
Hungary |
Latvia |
Poland |
Slovakia |
Spain |
Czechia |
|
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
|
The end of the study is defined as the last follow-up visit of the last participant enrolled (i.e., the last enrolled participant’s final visit) or a Sponsor decision to terminate the study, whichever comes first.
A participant is considered to have completed the study if he/she has completed all phases of the study, including the Week 44 safety follow-up assessment. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
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 | 2 |