Safety and Efficacy of IBE-814 Intravitreal (IVT) Implant - a Sustained, Low Dose Dexamethasone Therapy

NCT04576689 | Completed Phase 2 DMC

• 1 other identifier: IBE-814-IVT-1
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 21

Brief Summary

This trial is a phase II, multi-center, single-masked (assessors) dose-ranging study designed to evaluate the comparative safety and preliminary efficacy of two dosage regimens of the IBE-814 IVT Dexamethasone Implant in patients with DMO and RVO.

Conditions

Diabetic Macular Oedema; Retinal Vein Occlusion with Macular Oedema

Outcome Measures

Primary Outcomes (7)

• Best Corrected Visual Acuity

  Mean change in LogMAR best corrected visual acuity in the study eye

  Measurements from baseline to 6 months (24 weeks)

• Central Subfield Thickness

  Mean change in central subfield thickness on optical coherence tomography

  Measurements from baseline to 6 months (24 weeks)

• Ocular and Non-Ocular Treatment Emergent Adverse Events

  Number of ocular and non-ocular treatment emergent adverse events, summarized at the patient level by system organ class and preferred term

  Baseline through 18 months

• Study Drug-Related Ocular Adverse Events

  The number of study drug-related ocular adverse events, summarized separately for study and fellow eyes, by system organ class and preferred term

  Baseline through 18 months

• Drug-Related Adverse Events

  Drug-related adverse events including: a) any new rise in intraocular pressure \>27 mmHg in the study eye, at any visit; b) requirement for additional neuroprotective or IOP-lowering therapy, at any visit; c) requirement for surgery to reduce IOP, at any visit; d) any new diagnosis of cataract or significant lens opacification at any visit, significant worsening of cataract in the study eye during the study.

  Baseline through 18 months

• Post-Injection Complications

  Post-injection complications including worsening visual acuity, change in vision, worsening macular oedema, vitreous hemorrhage, retinal tear or detachments, inflammation, IOP alterations

  Baseline through 18 months

• Adverse Events

  Frequency and severity of adverse events throughout the primary outcome assessment period

  Baseline through 18 months

Study Arms (2)

Low dose

EXPERIMENTAL

One (1) IBE-814 IVT Implant (70 μg Dexamethasone) Route of administration: intravitreal injections

Drug: IBE-814 70ug

High dose

EXPERIMENTAL

Two (2) IBE-814 IVT Implant (140 μg Dexamethasone) Route of administration: intravitreal injections

Drug: IBE-814 140ug

Interventions

IBE-814 70ug DRUG

At least 10 and up to 33 participants will receive one (1) IBE-814. Route of administration: intravitreal injection.

Also known as: Low dose

Low dose

IBE-814 140ug DRUG

Up to 27 participants will receive two (2) IBE-814. Route of administration: intravitreal injection.

Also known as: High dose

High dose

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 45 years at the time of informed consent
• Able and willing to provide informed consent
• A diagnosis of CRVO defined as: The study eye has retinal hemorrhage or other biomicroscopic evidence of RVO (e.g. telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in all four quadrants AND Retinal thickening due to RVO involving the center of the macula of the study eye OR
• A diagnosis of BRVO defined as: The study eye has retinal hemorrhage or other biomicroscopic evidence of RVO (e.g. telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in one quadrant or less of retina drained by the affected vein AND Retinal thickening due to RVO involving the center of the macula of the study eye OR
• A diagnosis of HRVO defined as: The study eye has retinal hemorrhage or other biomicroscopic evidence of RVO (e.g. telangiectatic capillary bed) and a dilated venous system (or previously dilated venous system) in two adjacent quadrants of retina drained by the affected vein AND Retinal thickening due to RVO involving the center of the macula of the study eye OR
• A diagnosis of diabetes mellitus (Type 1 or type 2) defined as one or more of the following: a) Current regular use of insulin for the treatment of diabetes, b) Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes, c) Documented diabetes by ADA and/or WHO (World Health Organization) criteria, AND Retinal thickening due to DMO involving the center of the macula of the study eye.
• The study eye meets all of the following criteria:
• Visual acuity letter score in study eye ≤73 and ≥24 (approximate Snellen equivalent 20/40 to 20/320).
• Patient has CST of at least 300 μm (by Cirrus/Spectralis) if measured by Cirrus OCT or 325 μm if measured by Spectralis OCT, with presence of intraretinal and/or subretinal fluid at Screening visit and within 14 days of the baseline treatment visit.
• Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs.
• Study eye has not received any prior intravitreal injections of anti-VEGF or steroids (i.e., treatment naïve).
• Study eye has documented OCT evidence of an intravitreal anti-VEGF or steroid response with respect to macular oedema in the past 9 months. The response is defined as either a reduction of 30% or more of excess macular thickness or a reduction of 50 μm or greater. Excess macular thickness is defined as the amount of CST greater than 250 μm (by Cirrus/Spectralis).
• Must agree to use highly effective, medically accepted double-barrier contraception (both WOCBP and male partners of WOCBP) from Screening and for 12 months after last dose of study drug as specified below in this criterion.
• Highly effective double-barrier contraception is defined as use of a condom AND one of the following:
• Birth control pills (The Pill)

You may not qualify if:

• Known allergy or hypersensitivity to corticosteroids or any component of the study treatments (including povidone iodine prep) including any prior fluorescein allergic reaction graded above mild or that was not adequately resolved with oral or topical medication.
• Active or suspected ocular or periocular infection
• History of steroid-induced IOP elevation to ≥30 mmHg that required IOP-lowering treatment
• Systemic steroid treatment within 4 months prior to enrollment or anticipated use during the study
• Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months
• Systolic blood pressure \> 180mmHg or diastolic blood pressure \> 110 mmHg
• Screening glycated hemoglobin (HbA1c) blood test \>12.0%
• History of chronic renal failure requiring dialysis or kidney transplant
• Participation in an investigational trial within 30 days of enrolment that involved treatment with any drug that has not received regulatory approval for the indication being studied or participation in an investigational trial during this trial that may significantly impact safety and/or efficacy evaluations.
• Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 3 months prior to enrolment
• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.
• A condition that, in the opinion of the Investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control)
• Individual is expecting to move from the area of the study center to an area not covered by another center during the 18 months following randomization
• For the study eye only:
• Posterior capsule of the lens is absent, torn, ulcerated or perforated due to any cause, except if due to YAG capsulotomy.

Sponsors & Collaborators

• Ripple Therapeutics Pty Ltd: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (21)

Retina and Eye Consultants

Hurstville, New South Wales, 2220, Australia

Location

Eye Doctors Mona Vale

Mona Vale, New South Wales, 2103, Australia

Location

Marsden Eye Specialist

Parramatta, New South Wales, 2150, Australia

Location

Strathfield Retina Clinic

Strathfield, New South Wales, 2135, Australia

Location

Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

Location

Sydney Retina Clinic

Sydney, New South Wales, 2000, Australia

Location

Newcastle Eye Hospital

Waratah, New South Wales, 2298, Australia

Location

Queensland Eye Institute

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Adelaide Eye and Retina Centre

Adelaide, South Australia, 5000, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Centre For Eye Research Australia

East Melbourne, Victoria, 3002, Australia

Location

Armadale Eye Clinic

Malvern, Victoria, 3143, Australia

Location

Eye Surgery Associates

Malvern, Victoria, 3143, Australia

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Upton Eye Specialists

Brampton, Canada

Location

Retina Centre Of Ottawa

Ottawa, Canada

Location

Uptown Eye Specialists

Vaughan, Canada

Location

Grantham Hospital

Aberdeen, Hong Kong

Location

Prince of Wales Hospital the Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

Southern Eye Specialists

Christchurch, 8013, New Zealand

Location

Related Publications (1)

• Romano F, Lamanna F, Gabrielle PH, Teo KYC, Battaglia Parodi M, Iacono P, Fraser-Bell S, Cornish EE, Nassisi M, Viola F, Agarwal A, Samanta A, Chhablani J, Staurenghi G, Invernizzi A. Update on Retinal Vein Occlusion. Asia Pac J Ophthalmol (Phila). 2023 Mar-Apr 01;12(2):196-210. doi: 10.1097/APO.0000000000000598. Epub 2023 Feb 14.

  PMID: 36912792 DERIVED

MeSH Terms

Interventions

Contraceptives, Oral

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses

Study Officials

• Jagjit Gilhotra

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 6, 2020
• Study Start: October 30, 2020
• Primary Completion: April 25, 2023
• Study Completion: March 15, 2024
• Last Updated: March 21, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (15); HK (2); CA (3); NZ (1)