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

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ClinicalTrials.gov Identifier: NCT04611152
Recruitment Status : Terminated (Study did not meet primary endpoint)
First Posted : November 2, 2020
Last Update Posted : October 2, 2023
Sponsor:
Information provided by (Responsible Party):
Kodiak Sciences Inc

Study Description
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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.

Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Drug: KSI-301 Drug: Aflibercept Other: Sham Procedure Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 460 participants
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
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)
Actual Study Start Date : September 30, 2020
Actual Primary Completion Date : May 11, 2023
Actual Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: KSI-301
Intravitreal Injection

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.
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.
 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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).

  4. 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.

  5. 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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04611152


Locations
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Sponsors and Collaborators
Kodiak Sciences Inc
Investigators
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Study Director: Pablo Velazquez-Martin, MD Kodiak Sciences Inc
More Information
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Responsible Party: Kodiak Sciences Inc
ClinicalTrials.gov Identifier: NCT04611152    
Other Study ID Numbers: KS301P104
2020-001062-11 ( EudraCT Number )
First Posted: November 2, 2020    Key Record Dates
Last Update Posted: October 2, 2023
Last Verified: September 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kodiak Sciences Inc:
DME
Kodiak
Vascular endothelial growth factor
Anti-VEGF
VEGF
Antibody biopolymer conjugate
Retinal Degeneration
Retinal Diseases
Eye Diseases
Vision Disorders
 Vision, low
Aflibercept
Eylea
Diabetes mellitus
Diabetes
Diabetic retinopathy
Diabetic macular edema
Macular edema
KSI-301
Additional relevant MeSH terms:
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Macular Edema
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Aflibercept
 Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents