Title

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

    Phase 2
  • Study Type

    Interventional
  • Status

    Recruiting
  • Study Participants

    50
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.
The study will enroll up to 50 patients (up to 50 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 and New Zealand, specializing in the diagnosis and treatment of retinal diseases. All patients will be followed for a planned evaluation period of 18 months.
Study Started
Oct 30
2020
Primary Completion
Apr 30
2022
Anticipated
Study Completion
Jun 30
2023
Anticipated
Last Update
Aug 02
2021

Drug IBE-814

Up to 25 participants will receive IBE-814. Route of administration: intravitreal injection.

  • Other names: Low dose

Drug IBE-814

Up to 25 participants will receive IBE-814. Route of administration: intravitreal injection.

  • Other names: High dose

Low dose Experimental

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

High dose Experimental

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

Criteria

Inclusion Criteria:

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:

Current regular use of insulin for the treatment of diabetes.
Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes.
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 375 μm (by Cirrus/Spectralis) with presence of intraretinal and/or subretinal fluid at Screening visit and within 8 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).

Exclusion Criteria:

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 enrollment that involved treatment with any drug that has not received regulatory approval for the indication being studied
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.
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 edema or alter visual acuity during the study period (e.g., uveitis or other inflammatory eye disease, neovascular glaucoma, etc.)
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.
No Results Posted