A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME) (GLEAM)

• ClinicalTrials.gov Identifier: NCT04611152
• Recruitment Status: Terminated
• First Posted: November 2, 2020
• Last Update Posted: October 2, 2023
• Sponsor: Kodiak Sciences Inc
• Information provided by (Responsible Party): Kodiak Sciences Inc

Tracking Information

• First Submitted Date: October 19, 2020
• First Posted Date: November 2, 2020
• Last Update Posted Date: October 2, 2023
• Actual Study Start Date: September 30, 2020
• Actual Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 26, 2020)

Changes in BCVA to Assess Non-inferiority of KSI-301 to Aflibercept. [ Time Frame: Day 1 to Year 1 ]

Demonstrate that KSI-301 5 mg is non-inferior to aflibercept 2 mg with respect to mean change in best corrected visual acuity (BCVA).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 30, 2020)

• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in BCVA. [ Time Frame: Day 1 to Year 2 ]
  Change in best corrected visual acuity (BCVA).
• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in CST. [ Time Frame: Day 1 to Year 2 ]
  Change in central subfield thickness (CST).
• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in the diabetic retinopathy severity score (DRSS). [ Time Frame: Day 1 to Year 2 ]
  Change in diabetic retinopathy severity score (DRSS).
• Durability of KSI-301 5 mg compared to aflibercept 2 mg measured by number of intravitreal injections during the study. [ Time Frame: Day 1 to Year 2 ]
  Mean number of intravitreal injections during the course of the study.
• Safety and Tolerability of KSI-301 mg compared to aflibercept 2 mg measured by the number of ocular and systemic adverse events. [ Time Frame: Day 1 to Year 2 ]
  Incidence of ocular and systemic adverse events.

Original Secondary Outcome Measures (submitted: October 26, 2020)

• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in BCVA. [ Time Frame: Day 1 to Year 2 ]
  Improvement in best corrected visual acuity (BCVA).
• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in CST. [ Time Frame: Day 1 to Year 2 ]
  Improvement in , central subfield thickness (CST).
• Efficacy of KSI-301 5 mg compared to aflibercept 2 mg measured by changes in the diabetic retinopathy severity score (DRSS). [ Time Frame: Day 1 to Year 2 ]
  Improvement in diabetic retinopathy severity score (DRSS).
• Durability of KSI-301 5 mg compared to aflibercept 2 mg measured by number of intravitreal injections during the study. [ Time Frame: Day 1 to Year 2 ]
  Mean number of intravitreal injections during the course of the study.
• Safety and Tolerability of KSI-301 mg compared to aflibercept 2 mg measured by the number of ocular and systemic adverse events. [ Time Frame: Day 1 to Year 2 ]
  Incidence of ocular and systemic adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)
• Official Title: A Prospective, Randomized, Double-masked, Active Comparator-controlled, Multi-center, Two-arm, Phase 3 Study to Evaluate the Efficacy and Safety of Intravitreal KSI-301 Compared With Intravitreal Aflibercept in Participants With Visual Impairment Secondary to Treatment-naïve Diabetic Macular Edema (DME)
• Brief Summary: This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Detailed Description

This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with treatment-naïve DME.

The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomized 1:1 into one of two treatment arms: KSI-301 or aflibercept.

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:

For masking purposes, sham injections will be administered at every monthly visit if an active treatment is not administered. To preserve masking, two investigators are required for this study. The masked Investigator will be responsible for the examinations and safety assessments. The unmasked Investigator will perform the injections and post-treatment assessments.

Primary Purpose: Treatment

• Condition: Diabetic Macular Edema

Intervention

• Drug: KSI-301
  Intravitreal Injection
• Drug: Aflibercept
  Intravitreal Injection
  Other Name: Eylea
• Other: Sham Procedure
  The sham is a procedure that mimics an intravitreal injection. It involves pressing the blunt end of an empty syringe (without a needle) against the anesthetized eye. It will be administered to participants in both treatments arms at applicable visits to maintain masking.

Study Arms

• Experimental: KSI-301 (Arm A)
  Intravitreal injection of KSI-301 (5 mg) once every 4 weeks for 3 monthly doses followed by an individualized dosing regimen (every 8 to 24 weeks) via intravitreal injection from Week 16 to Week 100.
  Interventions:

  • Drug: KSI-301
  • Other: Sham Procedure
• Active Comparator: Aflibercept (Arm B)
  Intravitreal injection of aflibercept (2 mg) once every 4 weeks for 5 monthly doses followed by aflibercept (2 mg) once every 8 weeks via intravitreal injection from Week 24 to 100.
  Interventions:

  • Drug: Aflibercept
  • Other: Sham Procedure

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 2, 2022): 460
• Original Estimated Enrollment (submitted: October 26, 2020): 450
• Actual Study Completion Date: August 31, 2023
• Actual Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Signed informed consent prior to participation in the study.
2. Treatment-naïve diabetic macular edema, with vision loss and center involvement (if present) diagnosed within 9 months of screening.
3. BCVA ETDRS letter score between 78 and 25 (-20/25 to 20/320 Snellen equivalent), inclusive, in the Study Eye.
4. CST of ≥ 320 microns on SD-OCT (Heidelberg Spectralis or equivalent on other OCT instruments) as determined by the Reading Center.
5. Decrease in vision determined by the Investigator to be primarily the result of DME.
6. Type 1 or Type 2 diabetes mellitus and a HbA1c of ≤12%.
7. Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

1. Macular edema in the Study Eye considered to be secondary to a cause other than DME.
2. Active iris or angle neovascularization or neovascular glaucoma in the Study Eye.
3. High-risk proliferative diabetic retinopathy characteristics in the Study Eye.
4. History of Pan-retinal Photocoagulation (PRP) laser in the Study Eye within 3 months of screening.
5. Tractional retinal detachment in the Study Eye.
6. Active retinal disease other than the condition under investigation in the Study Eye.
7. Any history or evidence of a concurrent ocular condition present, 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).
8. Active or suspected ocular or periocular infection or inflammation in either eye at Day 1.
9. Any prior use of an approved or investigational treatment for DME in the Study Eye (e.g., anti-VEGF, intraocular or periocular steroids, macular laser photocoagulation).
10. Women who are pregnant or lactating or intending to become pregnant during the study.
11. Uncontrolled blood pressure defined as a systolic value ≥ 180 mmHg or diastolic value ≥100 mmHg while at rest.
12. 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.
13. 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.
14. Other protocol-specified exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Hungary, Italy, Latvia, Puerto Rico, Slovakia, Spain, United States

Administrative Information

• NCT Number: NCT04611152
• Other Study ID Numbers: KS301P104; 2020-001062-11 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kodiak Sciences Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Kodiak Sciences Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pablo Velazquez-Martin, MD; Kodiak Sciences Inc

• PRS Account: Kodiak Sciences Inc
• Verification Date: September 2023