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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04576689




Registration number
NCT04576689
Ethics application status
Date submitted
30/09/2020
Date registered
6/10/2020

Titles & IDs
Public title
Safety and Efficacy of IBE-814 Intravitreal (IVT) Implant - A Sustained, Low Dose Dexamethasone Therapy
Scientific 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
Secondary ID [1] 0 0
IBE-814-IVT-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Macular Oedema 0 0
Retinal Vein Occlusion With Macular Oedema 0 0
Condition category
Condition code
Eye 0 0 0 0
Diseases / disorders of the eye
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IBE-814 70ug
Treatment: Drugs - IBE-814 140ug

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

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


Treatment: Drugs: IBE-814 70ug
Up to 25 participants will receive IBE-814. Route of administration: intravitreal injection.

Treatment: Drugs: IBE-814 140ug
Up to 25 participants will receive IBE-814. Route of administration: intravitreal injection.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Best Corrected Visual Acuity
Timepoint [1] 0 0
Measurements from baseline to 6 months (24 weeks)
Primary outcome [2] 0 0
Central Subfield Thickness
Timepoint [2] 0 0
Measurements from baseline to 6 months (24 weeks)
Primary outcome [3] 0 0
Ocular and Non-Ocular Treatment Emergent Adverse Events
Timepoint [3] 0 0
Baseline through 18 months
Primary outcome [4] 0 0
Study Drug-Related Ocular Adverse Events
Timepoint [4] 0 0
Baseline through 18 months
Primary outcome [5] 0 0
Drug-Related Adverse Events
Timepoint [5] 0 0
Baseline through 18 months
Primary outcome [6] 0 0
Post-Injection Complications
Timepoint [6] 0 0
Baseline through 18 months
Primary outcome [7] 0 0
Adverse Events
Timepoint [7] 0 0
Baseline through 18 months

Eligibility
Key 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:

1. Current regular use of insulin for the treatment of diabetes.
2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes.
3. 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:

1. Visual acuity letter score in study eye =73 and =24 (approximate Snellen equivalent 20/40 to 20/320).
2. 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.
3. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs.
4. 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:

1. Birth control pills (The Pill)
2. Depot or injectable birth control
3. IUD (Intrauterine Device)
4. Birth Control Patch
5. NuvaRing
6. Implantable contraception (e.g., Implanon)
7. 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).
Minimum age
45 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/03/2024
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Retina and Eye Consultants - Hurstville
Recruitment hospital [2] 0 0
Eye Doctors Mona Vale - Mona Vale
Recruitment hospital [3] 0 0
Marsden Eye Specialist - Parramatta
Recruitment hospital [4] 0 0
Strathfield Retina Clinic - Strathfield
Recruitment hospital [5] 0 0
Sydney Eye Hospital - Sydney
Recruitment hospital [6] 0 0
Sydney Retina Clinic - Sydney
Recruitment hospital [7] 0 0
Newcastle Eye Hospital - Waratah
Recruitment hospital [8] 0 0
Queensland Eye Institute - South Brisbane
Recruitment hospital [9] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [10] 0 0
Adelaide Eye and Retina Centre - Adelaide
Recruitment hospital [11] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [12] 0 0
Centre For Eye Research Australia - East Melbourne
Recruitment hospital [13] 0 0
Armadale Eye Clinic - Malvern
Recruitment hospital [14] 0 0
Eye Surgery Associates - Malvern
Recruitment hospital [15] 0 0
Lions Eye Institute - Nedlands
Recruitment postcode(s) [1] 0 0
2220 - Hurstville
Recruitment postcode(s) [2] 0 0
2103 - Mona Vale
Recruitment postcode(s) [3] 0 0
2150 - Parramatta
Recruitment postcode(s) [4] 0 0
2135 - Strathfield
Recruitment postcode(s) [5] 0 0
2000 - Sydney
Recruitment postcode(s) [6] 0 0
2298 - Waratah
Recruitment postcode(s) [7] 0 0
4101 - South Brisbane
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
3002 - East Melbourne
Recruitment postcode(s) [11] 0 0
3143 - Malvern
Recruitment postcode(s) [12] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Brampton
Country [2] 0 0
Canada
State/province [2] 0 0
Ottawa
Country [3] 0 0
Canada
State/province [3] 0 0
Vaughan
Country [4] 0 0
Hong Kong
State/province [4] 0 0
Aberdeen
Country [5] 0 0
Hong Kong
State/province [5] 0 0
Hong Kong
Country [6] 0 0
New Zealand
State/province [6] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ripple Therapeutics Pty Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jagjit Gilhotra
Address 0 0
Royal Adelaide Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04576689