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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 : Recruiting
First Posted : November 2, 2020
Last Update Posted : September 2, 2021
Sponsor:
Information provided by (Responsible Party):
Kodiak Sciences Inc

Tracking Information
First Submitted Date  ICMJE October 19, 2020
First Posted Date  ICMJE November 2, 2020
Last Update Posted Date September 2, 2021
Actual Study Start Date  ICMJE September 30, 2020
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Trial to Evaluate the Efficacy, Durability, and Safety of KSI-301 Compared to Aflibercept in Participants With Diabetic Macular Edema (DME)
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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  ICMJE Diabetic Macular Edema
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 26, 2020)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2023
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kodiak Sciences Inc 1 (650) 281-0850 ksi301clinical@kodiak.com
Listed Location Countries  ICMJE Latvia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04611152
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Kodiak Sciences Inc
Study Sponsor  ICMJE Kodiak Sciences Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pablo Velazquez-Martin, MD Kodiak Sciences Inc
PRS Account Kodiak Sciences Inc
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP