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Diabetic Macular OedemaPhase 2NCT04576689

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

A Phase 2 study testing IBE-814 70ug and IBE-814 140ug in people with Diabetic Macular Oedema and Retinal Vein Occlusion with Macular Oedema, run by Ripple Therapeutics Pty Ltd at 21 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 years and older
What is being tested?
IBE-814 70ug and IBE-814 140ug
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
21 sitesin 4 countries
Study dates
30 Oct 2020to 15 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • OR
  • 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)
  • Depot or injectable birth control
  • IUD (Intrauterine Device)
  • Birth Control Patch
  • NuvaRing
  • Implantable contraception (e.g., Implanon)
  • Documented evidence of surgical sterilization at least 6 months prior to Screening, i.e., tubal ligation or hysterectomy for women or vasectomy for men
  • Rhythm methods are not considered as highly effective methods of birth control. Male subjects must refrain from sperm donation from start of study and for 12 months after the last dose of study drug. Subjects who are in same-sex relationships are not required to use contraception. Contraception does not apply to postmenopausal females (i.e. FSH ≥30 mIU/mL and ≥12 months since last menstruation).

Who cannot join

  • 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
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  • 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.
  • Aphakia or anterior chamber IOL
  • For patients with RVO in the study eye, presence of diabetic retinopathy in either eye
  • Macular oedema is considered to be due to a cause other than DMO or RVO
  • Macula is non-perfused on Screening fluorescein angiography.
  • An ocular condition is present (e.g., foveal atrophy, pigment abnormalities, dense sub-foveal hard exudates, visually significant cataract, non-retinal condition, etc.), such that visual acuity loss would not improve from resolution of macular oedema.
  • An ocular condition is present (other than DMO or RVO) that, in the opinion of the Investigator, might affect macular oedema or alter visual acuity during the study period (e.g., uveitis or other inflammatory eye disease, neovascular glaucoma, etc.), or it is expected that the patient will require a procedure within 24-weeks post-enrolment that may affect macular oedema or alter visual acuity (e.g., retinal photocoagulation treatment). After 24 weeks of enrolment, procedures may be performed after notifying the Sponsor and Medical Monitor.
  • Presence of an epiretinal membrane or vitreo-retinal interface changes in the study eye which, in the opinion of the Investigator, is the primary cause of macular oedema, or is severe enough to prevent improvement in visual acuity despite reduction in macular oedema
  • Substantial posterior capsule opacity that, in the opinion of the Investigator, is likely to be decreasing visual acuity by three lines or more (i.e., opacity would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  • IOP greater than 21 mmHg while treated with more than one topical medical therapy.
  • A documented diagnosis of glaucoma or IOP>21 mmHg and presence of glaucomatous optic nerve head observed by fundus examination.
  • History of intraocular corticosteroid injection or implant within 6 months prior to study treatment.
  • History of greater than one (1) OZURDEX® dexamethasone implant for phakic patients only. There is no limit for pseudophakic patients.
  • History of IVT anti-VEGF injections within 6 weeks prior to study treatment.
  • Any history of treatment with Retisert, Iluvien or Yutiq insert for phakic patients, or any treatment with Retisert, Iluvien or Yutiq in the previous 36 months for pseudophakic patients.
  • History of macular laser photocoagulation within 4 months prior to study treatment.
  • Any history of vitrectomy.
  • History of cataract surgery within 3 months of enrolment or predicted within 6 months post-enrolment.
  • History of YAG laser posterior capsulotomy within 3 months of enrolment or predicted within 6 months post-enrolment, or a prior YAG capsulotomy that does not sufficiently cover the borders of the IOL optic.
  • Anterior capsule requires treatment for concurrent phimosis.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

Australia15 sites

  • Adelaide Eye and Retina Centre

    Adelaide, South Australia, 5000

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Centre For Eye Research Australia

    East Melbourne, Victoria, 3002

  • Retina and Eye Consultants

    Hurstville, New South Wales, 2220

  • Armadale Eye Clinic

    Malvern, Victoria, 3143

  • Eye Surgery Associates

    Malvern, Victoria, 3143

  • Eye Doctors Mona Vale

    Mona Vale, New South Wales, 2103

  • Lions Eye Institute

    Nedlands, Western Australia, 6009

  • Marsden Eye Specialist

    Parramatta, New South Wales, 2150

  • Queensland Eye Institute

    South Brisbane, Queensland, 4101

  • Strathfield Retina Clinic

    Strathfield, New South Wales, 2135

  • Sydney Eye Hospital

    Sydney, New South Wales, 2000

  • Sydney Retina Clinic

    Sydney, New South Wales, 2000

  • Newcastle Eye Hospital

    Waratah, New South Wales, 2298

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada3 sites

  • Upton Eye Specialists

    Brampton

  • Retina Centre Of Ottawa

    Ottawa

  • Uptown Eye Specialists

    Vaughan

Other trials in Canada

Hong Kong2 sites

  • Grantham Hospital

    Aberdeen

  • Prince of Wales Hospital the Chinese University of Hong Kong

    Hong Kong

Other trials in Hong Kong

New Zealand1 site

  • Southern Eye Specialists

    Christchurch, 8013

Other trials in New Zealand

About this study

Official title: RIPPLE-1: Evaluation of Safety and Efficacy of the IBE-814 Intravitreal Implant in Patients with Diabetic Macular Oedema and Macular Oedema Due to Retinal Vein Occlusion

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.

Read the detailed description

The study will enroll up to 60 patients (up to 60 eyes) with DMO or RVO across two treatment groups (Low Dose and High Dose). Patients will be identified and recruited through the clinic population of ophthalmology centers in Australia, New Zealand, Hong Kong, and Canada specializing in the diagnosis and treatment of retinal diseases. All patients will be followed for a planned evaluation period of 18 months.

Being tested
IBE-814 70ug, IBE-814 140ug

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IBE-814 70ugDrug

    Also called Low dose

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

  • IBE-814 140ugDrug

    Also called High dose

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

Study groups in NCT04576689
Study groupRoleWhat they receive
Low doseExperimentalOne (1) IBE-814 IVT Implant (70 μg Dexamethasone) Route of administration: intravitreal injections
Receives: Drug: IBE-814 70ug
High doseExperimentalTwo (2) IBE-814 IVT Implant (140 μg Dexamethasone) Route of administration: intravitreal injections
Receives: Drug: IBE-814 140ug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best Corrected Visual Acuity

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

    Measured: Measurements from baseline to 6 months (24 weeks)

  2. Central Subfield Thickness

    Mean change in central subfield thickness on optical coherence tomography

    Measured: Measurements from baseline to 6 months (24 weeks)

  3. 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

    Measured: Baseline through 18 months

  4. 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

    Measured: Baseline through 18 months

  5. 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.

    Measured: Baseline through 18 months

  6. 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

    Measured: Baseline through 18 months

  7. Adverse Events

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

    Measured: Baseline through 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2020
  2. Study start30 Oct 2020
  3. Primary completion25 Apr 2023
  4. Study completion15 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04576689
Sponsor's protocol ID
IBE-814-IVT-1
Status last verified
Jun 2024
First submitted
30 Sep 2020
Last updated
21 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 36912792

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IBE-814 70ug and IBE-814 140ug in people with Diabetic Macular Oedema and Retinal Vein Occlusion with Macular Oedema, run by Ripple Therapeutics Pty Ltd at 21 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Australia, Canada, Hong Kong, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Corrected Visual Acuity (time frame: Measurements from baseline to 6 months (24 weeks)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04576689, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2025.

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