Evaluation of Dexamethasone Intravitreal Implant Loading Dose Efficacy in Diabetic Macular Edema: A Pilot and Phase 2 Study
- Trial ID
- 2024-514362-39-00
- Protocol
- 69HCL19_0588
- Sponsor
- Hospices Civils De Lyon
Trial statistics
Objectives
The primary objective of this study is to evaluate the **efficacy** of a new Ozurdex® intravitreal implant treatment regimen over 52 weeks in patients with **diabetic macular oedema**, specifically focusing on improvements in visual acuity. This is clinically relevant as diabetic macular oedema is a leading cause of vision impairment in diabetic patients, and effective treatment can significantly enhance quality of life and reduce the risk of vision loss.
Secondary objectives include:
- Describing the time required to achieve the best **best-corrected visual acuity (BCVA)**.
- Assessing changes in visual acuity over a 24-month period.
- Documenting the total number of injections administered between inclusion and 52 weeks, and over 24 months if treatment continues.
- Evaluating patient discomfort associated with the Ozurdex® intravitreal implant.
- Describing the qualitative evolution of anatomical lesions via **optical coherence tomography (OCT)** over 24 months.
- Monitoring the progression of macular oedema at 52 weeks and 24 months.
- Assessing the evolution of the severity of **diabetic retinopathy** at 52 weeks and 24 months.
- Describing areas of diabetic vascularisation and non-perfusion over 24 months using OCT-A angiography.
- Evaluating the condition of the lens implant and posterior capsule.
- Monitoring the evolution of intraocular pressure over 24 months and the use of hypotonising treatment during the study.
- Assessing the tolerability of intravitreal dexamethasone treatment.
Participants
The clinical trial focuses on evaluating the efficacy of a new **Ozurdex® intravitreal implant** treatment regimen for patients with **diabetic macular oedema**. The study population includes both male and female participants over the age of 40, with a specific emphasis on individuals who are pseudophakic for at least three months and have not previously received intravitreal corticosteroid or anti-VEGF treatment. Participants are required to have a central macular thickness of at least 285 µm or 275 µm, depending on the measurement method, and a visual acuity between 20/32 and 20/230. The trial includes individuals with an HbA1c level below 10% and blood pressure under 160/95 mmHg. Participants must be willing to attend all study visits and complete all related procedures, and they must provide informed consent. The trial includes a vulnerable population, and participants are required to be affiliated with a social security scheme or equivalent. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of a **dexamethasone** intravitreal implant treatment regimen in patients with **diabetic macular oedema**. This study is a Phase 4, randomized, double-blind, controlled trial with an estimated duration of 52 weeks for each participant. The trial aims to assess the improvement in visual acuity over a one-year period, with the primary endpoint being the difference in Best Corrected Visual Acuity (BCVA) from baseline to the highest value observed during the follow-up period. Secondary endpoints include the time to reach the highest BCVA value, the number of injections required, and patient discomfort related to the implant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, central macular thickness, and visual acuity. The inclusion visit will also ensure that participants have not received prior intravitreal corticosteroid or anti-VEGF treatment and meet other health criteria. Monthly follow-up visits will be conducted during the first year to monitor visual acuity, central macular thickness, and any adverse events. The end-of-study visit will occur at 52 weeks, where final assessments will be made, including a comprehensive evaluation of visual acuity and ocular health.
The expected length of participant involvement is approximately 52 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. Participants are required to adhere to the study protocol, including attending all scheduled visits and completing all related procedures. The trial is set to begin recruitment in September 2024, with an estimated completion date in December 2026. The study will utilize the **OZURDEX 700 micrograms intravitreal implant in applicator** as the investigational product, administered via intravitreal use. The trial will follow a structured dosing regimen, with a maximum treatment period of 48 weeks, ensuring adherence to safety and efficacy standards.
Treatment
The clinical trial involves the use of **OZURDEX**, a 700 micrograms **intravitreal implant** in an applicator, as the experimental medication. The active substance in OZURDEX is **dexamethasone**, a chemical compound classified under the ATC code S01BA01. The pharmaceutical form of the medication is an intravitreal implant, which is administered via intravitreal use. The maximum daily dose is 700 micrograms, with a total maximum dose of 3500 micrograms over the treatment period. The treatment period is set for a maximum of 48 weeks. The administration of OZURDEX involves a specific dosing schedule, which includes the use of a broad-spectrum antibiotic eye drop for three days prior to the injection, although this is not systematic. The administration of the eye drop follows the recommendations of the French Society of Ophthalmology (SFO).
In addition to the experimental treatment, the study protocol includes the administration of a broad-spectrum antibiotic eye drop prior to the OZURDEX injection. This non-experimental treatment is intended to prevent potential infections associated with the intravitreal injection procedure. The use of the antibiotic eye drop is not systematic and is guided by the recommendations of the SFO. Compliance with the dosing schedule and administration guidelines is monitored throughout the study to ensure participant safety and the integrity of the trial results.
Efficacy
The efficacy of the treatment protocol with the **dexamethasone** implant in patients with diabetic macular edema will be assessed over a period of 52 weeks. The primary endpoint for evaluating efficacy is the difference between the highest value of Best Corrected Visual Acuity (BCVA) observed during follow-up to 52 weeks and the BCVA observed at inclusion. Corrected visual acuity will be measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at a distance of 4 meters.
Secondary endpoints include the time required to reach the highest BCVA value during the first 52 weeks, the number of injections, and the description of visual acuity (VA) changes at various time points such as S12, S24, S36, S52, M18, and M24. Additional assessments involve the total number of injections performed per patient, patient discomfort measured by a visual analog scale (VAS), and variations in central macular thickness (CMT) and central foveolar thickness. The study will also evaluate the resolution of macular edema, changes in diabetic retinopathy grades, and qualitative and quantitative analysis of diabetic vascularization and non-perfusion zones on OCT-angiography. Intraocular pressure changes and adverse events will be monitored throughout the study.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient over 40 years old
- Patient with significant diabetic macular oedema (DMO): * a central macular thickness (CMT) ≥ 285 μm measured by Spectralis/Topcon SD-OCT (spectral-domain optical coherence tomography), or a CMT ≥ 275 μm measured by Cirrus SD-OCT. * visual acuity between 20/32 and 20/230 (between 23 and 78 letters) measured using the ETDRS scale and complying with the measurement protocol at a distance of 4 metres.
- Patient for which it has been decided to insert an intra-retinal dexamethasone implant
- eye naive to any drug treatment (no previous intravitreal corticosteroid or anti-VEGF treatment)
- patient pseudophakic for at least 3 months
- HBA1c < 10%
- blood pressure <160/95 mmHg
- Patient who have given their free, informed and signed consent
- Patient affiliated to a social security scheme or equivalent
- Patient willing and able to return for all study clinical visits and to complete all related procedures.
Exclusion Criteria
- Study eye aphakic with missing posterior lens capsule
- History of focal laser located in the study eye less than 750 microns from the fovea (1/2 Papillary Diameter)
- Ischaemic maculopathy (more than 2-fold increase in the surface area of the central avascular zone)
- Proliferative diabetic retinopathy (presence of pre-retinal neovessels) in the study eye
- Eye studied with an anterior chamber implant or intraocular implant with iridal or transcleral fixation or rupture of the posterior lens capsule
- Eye studied with an ARTISAN® type lens implant
- Active or suspected periocular or ocular infection on the side being studied, including but not limited to most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and mycoses.
- Cataract surgery on the eye studied < 3 months
- Last session of panretinal laser photocoagulation of the study eye < 1 month
- Last session of focal laser treatment of the posterior pole of the study eye < 1 month
- Vitreo-macular traction syndrome associated with an epiretinal membrane in the study eye
- History of laser treatment in the macular grid of the study eye
- Ocular hypertension or open-angle glaucoma of the studied eye treated with at least one dual therapy.
- Patients with systemic pathology likely to interfere with the evolution of DME and treated with immunosuppressants, systemic corticoids, anti-aldosterone, systemic anti-VEGF, etc.
- Patients undergoing systemic treatment with a toxic effect on the retina or optic nerve: deferoxamine, chloroquine /hydroxychloroquine, tamoxifen and ethambutol; currently or in the 6 months prior to inclusion.
- Known hypersensitivity to the active substance or to one of the excipients or to anesthetic or hypotonizing eye drops.
- History of any pathology, metabolic disease, or any serious suspicion of disease on clinical or laboratory examination, which would contraindicate the use of the dexamethasone intraretinal implant, could affect the interpretation of study results or entail significant risks of complication for the subject.
- Active or suspected infectious conjunctivitis and/or adnexal infection
- Any ocular disease or condition of the study eye which, in the opinion of the investigator, may require intraocular surgery within 12 months
- Contralateral eye with visual acuity < 23 letters
- Pregnant or breast-feeding women
- Women of childbearing age, sexually active, unwilling to commit to the use of adequate and highly effective contraception during the study and up to 6 months after the last administration of study treatment: o Combined hormonal contraception (containing estrogen and progestin) for ovulation inhibition (oral, intravaginal or transdermal); o Hormonal contraception containing only a progestin to inhibit ovulation (oral, injectable or implantable); o Intrauterine device (IUD); o Intrauterine hormone delivery system (IUD); o Ovariectomy with hysterectomy, bilateral tubal occlusion or total hysterectomy for at least 6 weeks prior to inclusion, or vasectomy for at least 6 months prior to inclusion (for partners of an included patient); o Sexual abstinence. A woman will be considered to be of childbearing age from the time of her first menstrual period until the menopausal period, unless she is sterile or has had surgery such as oophorectomy with hysterectomy, bilateral tubal occlusion or total hysterectomy at least 6 weeks prior to inclusion. A post-menopausal state is defined as the absence of spontaneous menses (i.e., without other medical treatment such as hormonal contraception or hormone replacement therapy) for 12 months.
- Patient of legal age (Code de la Santé Publique)
- Patient currently participating in another interventional clinical trial (eye studied and/or eye not studied).
- Follow-up not possible for 24 months, at the investigator's discretion
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 30 Nov 2020 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
OZURDEX 700 micrograms intravitreal implant in applicator | Test | INTRAVITREAL IMPLANT IN APPLICATOR | INTRAVITREAL USE | 700 | 48 | PRD9771151 |