A Study to Evaluate the Efficacy and Safety of KSI-301 Compared with Sham Treatment in Participants with Moderately Severe to Severe Non-proliferative Diabetic Retinopathy (NPDR)

Phase 1

Conditions: on-proliferative Diabetic Retinopathy (NPDR)
MedDRA version: 20.1Level: PTClassification code 10012689Term: Diabetic retinopathySystem Organ Class: 10015919 - Eye disorders
MedDRA version: 20.0Level: SOCClassification code 10015919Term: Eye disordersSystem Organ Class: 10015919 - Eye disorders
MedDRA version: 20.0Level: HLTClassification code 10012657Term: Diabetic complications ophthalmicSystem Organ Class: 100000004860
MedDRA version: 20.0Level: PTClassification code 10012661Term: Diabetic eye diseaseSystem Organ Class: 10015919 - Eye disorders
MedDRA version: 20.0Level: LLTClassification code 10038925Term: Retinopathy diabeticSystem Organ Class: 10015919 - Eye disorders
MedDRA version: 20.1Level: LLTClassification code 10054109Term: Non-proliferative diabetic retinopathySystem Organ Class: 10015919 - Eye disorders
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2020-001064-29-ES

Lead Sponsor: Kodiak Sciences Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

1. Participants with moderately severe to severe NPDR in the Study Eye (DRSS levels 47 and 53 as determined by the reading center based on color fundus photographs), who have not previously received intravitreal medications for DR or DME, and in whom pan-retinal photocoagulation (PRP) can be safely deferred for at least 6 months per the Investigator.
2. BCVA ETDRS letter score in the Study Eye of =69 letters (approximate Snellen equivalent of 20/40 or better) in the Study Eye at Screening and confirmed at Day 1. Only one eye per subject is eligible to participate in the study. If both eyes are eligible to become the Study Eye, the eye with worse BCVA and/or worse DR severity at Screening will be selected as the Study Eye. If both eyes are eligible and have the same BCVA and/or DR severity or one eye has worse BCVA and the fellow eye has worse DR, the decision of which eye to select as the Study Eye will be made by the Investigator.
3. Male or female =18 years of age.
4. 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
5. Type 1 or 2 diabetes mellitus and HbA1c of =12%.
6. 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 intervention.
a. A woman is considered of childbearing potential if she is post-menarchal, has not reached a post-menopausal 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 post-ovulation methods) and withdrawal are not acceptable methods of contraception.
7. 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 intervention. Men must refrain from donating sperm during this same time period.
8. Ability and willingness to undertake all the scheduled visits and assessments.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Num

Exclusion Criteria

1. Presence of center-involved DME in the study eye, defined for this purpose as CST of =320 microns on SD-OCT (Heidelberg Spectralis or equivalent value on other OCT instruments).
2. Prior PRP in the Study Eye.
3. Current anterior segment neovascularization (ASNV), vitreous hemorrhage, or tractional retinal detachment in the Study Eye.
4. Prior intravitreal anti-VEGF treatment in the Study Eye for DR or DME.
5. Prior intravitreal or periocular steroid in the Study Eye for DR or DME.
6. Prior use of an investigational intravitreal treatment for DR or DME in the Study Eye.
7. History of vitreoretinal surgery in the Study Eye
8. History of retinal detachment or treatment or surgery for retinal detachment in the Study Eye.
9. History of cataract surgery in the Study Eye within 2 months of screening.
10. History of YAG laser capsulotomy in the Study Eye within 2 months of screening.
11. Uncontrolled glaucoma (defined as intraocular pressure =25 mmHg despite treatment with antiglaucoma medication) in the Study Eye.
12. History of glaucoma-filtering surgery (trabeculectomy or tube shunt) in the Study Eye.
13. History of uveitis in either eye.
14. Significant media opacities, including cataract, in the Study Eye that might interfere with visual acuity, assessment of safety, OCT, or FP.
15. Cataract in the Study Eye that in the judgment of the Investigator is expected to require surgical extraction within 12 months of screening.
16. Aphakia in the Study Eye.
17. Active retinal disease other than the condition under investigation in the Study Eye.
18. 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 alter visual acuity during the study (e.g., vitreomacular traction, epiretinal membrane).
19. Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
20. BCVA of hand motion or worse in the non-Study Eye or non-physical presence of a non-Study Eye (i.e., monocular).
21. Women who are pregnant or lactating or intending to become pregnant during the study.
22. Women of child-bearing 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.
23. 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.
24. Kidney failure requiring renal transplant, hemodialysis or peritoneal dialysis or expected to require renal transplant, hemodialysis or peritoneal dialysis 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 intravitreal agents such as aflibercept or ranibizuma

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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