Investigative Ophthalmology & Visual Science Cover Image for Volume 65, Issue 7
June 2024
Volume 65, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2024
Efficacy and safety of a low dose dexamethasone implant for diabetic macular edema and retinal vein occlusion: Results of the First-In-Human Phase 2 RIPPLE-1 trial
Author Affiliations & Notes
  • Hemal Mehta
    Strathfield Retina Clinic, New South Wales, Australia
    The University of Sydney Save Sight Institute, Sydney, New South Wales, Australia
  • Kelli Wootton
    Ripple Therapeutics, Ontario, Canada
  • Madeline Simpson
    Ripple Therapeutics, Ontario, Canada
  • Gillian Mackey
    Ripple Therapeutics, Ontario, Canada
  • Wendy Naimark
    Ripple Therapeutics, Ontario, Canada
  • Footnotes
    Commercial Relationships   Hemal Mehta AbbVie, Apellis Pharmaceuticals, Bayer, Iveric Bio, Roche, Code C (Consultant/Contractor), Ripple Therapeutics, Code F (Financial Support); Kelli Wootton Ripple Therapeutics, Code E (Employment), Ripple Therapeutics, Code P (Patent); Madeline Simpson Ripple Therapeutics, Code E (Employment), Ripple Therapeutics, Code P (Patent); Gillian Mackey Ripple Therapeutics, Code E (Employment), Ripple Therapeutics, Code P (Patent); Wendy Naimark Ripple Therapeutics, Code E (Employment), Ripple Therapeutics, Code O (Owner), Ripple Therapeutics, Code P (Patent)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2024, Vol.65, 6253. doi:
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      Hemal Mehta, Kelli Wootton, Madeline Simpson, Gillian Mackey, Wendy Naimark; Efficacy and safety of a low dose dexamethasone implant for diabetic macular edema and retinal vein occlusion: Results of the First-In-Human Phase 2 RIPPLE-1 trial. Invest. Ophthalmol. Vis. Sci. 2024;65(7):6253.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The IBE-814 Intravitreal (IVT) Implant is a fully degradable, injectable, 30-gauge implant that delivers a sustained, low dose of dexamethasone without the use of a polymer carrier for at least 6 months. The RIPPLE-1 trial was designed to evaluate the safety, efficacy, and durability of the implant in subjects with diabetic macular edema (DME) or retinal vein occlusion (RVO) and to select the optimal drug dose for future studies.

Methods : The RIPPLE-1 trial was a Phase 2, randomized, single-masked, multi-center, dose-ranging study of the IBE-814 IVT Implant. Treatment naïve and previously treated DME and RVO subjects were randomized to receive one (Low Dose, LD) or two (High Dose, HD) 70 μg implants at baseline. The key study endpoints were mean change in central subfield thickness (CST) and best-corrected visual acuity (BCVA) at 6 months, as well as safety endpoints throughout the study. Subjects were eligible for retreatment with the IBE-814 IVT Implant between 5 and 12 months, based on anatomical and functional criteria.

Results : Sixty subjects in four cohorts were treated with the IBE-814 IVT Implant: RVO Low Dose (n=10), DME Low Dose (n=23), RVO High Dose (n=15), and DME High Dose (n=12). At the 6-month key efficacy endpoint, all cohorts demonstrated reduced CST, with mean (SE) thickness reductions from Baseline of -188 (60) μm (RVO LD), -68 (20) μm (DME LD), -148 (45) μm (RVO HD), and -94 (23) μm (DME HD). All cohorts showed improved or stable mean BCVA. At 6 months, the mean (SE) changes in BCVA from Baseline were +6.4 (3.9) letters (RVO LD), -1.9 (2.0) letters (DME LD), +5.5 (1.9) letters (RVO HD), and +8.7 (1.0) letters (DME HD). After one treatment with IBE-814, at least 60% of subjects in each cohort reached the 6-month visit without receiving additional treatment. The most common treatment-related adverse events were known steroid side-effects: elevated intraocular pressure and cataracts.

Conclusions : The IBE-814 IVT Implant demonstrated sustained reductions in CST, with improved or stable BCVA, for at least 6 months in DME and RVO and has been well-tolerated to date. The results of the study will be presented along with efficacy and safety trends that will inform dose selection for future trials.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Mean change in CST from Baseline to Month 6 (RVO cohorts)

Mean change in CST from Baseline to Month 6 (RVO cohorts)

 

Mean change in CST from Baseline to Month 6 (DME cohorts)

Mean change in CST from Baseline to Month 6 (DME cohorts)

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