Neovascular (Wet) Age-related Macular Degeneration (wAMD) MedDRA version: 20.0 Level: SOC Classification code 10015919 Term: Eye disorders System Organ Class: 10015919 - Eye disorders MedDRA version: 20.0 Level: PT Classification code 10071129 Term: Neovascular age-related macular degeneration System Organ Class: 10015919 - Eye disorders MedDRA version: 20.1 Level: PT Classification code 10064930 Term: Age-related macular degeneration System Organ Class: 10015919 - Eye disorders MedDRA versi
Conditions
Sponsors
Kodiak Sciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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. 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)
Exclusion criteria
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 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. 24. Women who are pregnant or lactating or intending to become pregnant during the study 25. 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. 26. 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. 27. 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. 28. 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-therapeuti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;Primary end point(s): Mean change in BCVA from baseline (Day 1) to Week 40, in Early Treatment Diabetic Retinopathy Study (ETDRS) Letters.;Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed using ETDRS data collected up to Week 40. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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).;Timepoint(s) of evaluation of this end point: Key secondary endpoints will be assessed at Week 40 (for efficacy) or Week 44 (for safety) | — |
Countries
Czechia, Hungary, Latvia, Poland, Slovakia, Spain, United States
Contacts
Public ContactKSI-CL-105 Trial Information
Kodiak Sciences Inc.
Outcome results
None listed