Loadex: Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol with Dexamethasone Implant Loading Dose in Patients with Diabetic Macular Edema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

5 Dec 2019 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514362-39-00

EudraCT number

2019-003092-18

ClinicalTrials.gov

NCT04116398

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To describe the efficacy at 1 year (52 weeks) of a new Ozurdex® intravitreal implant treatment regimen, in terms of visual acuity, in patients with diabetic macular oedema.

Secondary objectives 11

1. Describe time required to obtain the best BCVA
2. Describe the change in visual acuity over 24 months
3. Describe the total number of injections between inclusion and 52 weeks, and for 24 months (if dexamethasone intravitreal implant treatment is continued)
4. To describe the discomfort felt by the patient in relation to the Ozurdex® intravitreal implant.
5. Describe the qualitative evolution of anatomical lesions by OCT over 24 months
6. Describe the evolution of macular oedema at 52 weeks and 24 months
7. To describe the evolution of the severity of diabetic retinopathy at 52 weeks and 24 months
8. Describe the areas of diabetic vascularisation and non-perfusion over 24 months (OCT-A angiography)
9. Describe the condition of the lens implant and posterior capsule
10. Describe the evolution of intraocular pressure over 24 months, and the use of hypotonising treatment during the study
11. To describe the tolerability of intravitreal dexamethasone treatment

Conditions and MedDRA coding

Diabetic macular oedema

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient over 40 years old
2. 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.
3. Patient for which it has been decided to insert an intra-retinal dexamethasone implant
4. eye naive to any drug treatment (no previous intravitreal corticosteroid or anti-VEGF treatment)
5. patient pseudophakic for at least 3 months
6. HBA1c < 10%
7. blood pressure <160/95 mmHg
8. Patient who have given their free, informed and signed consent
9. Patient affiliated to a social security scheme or equivalent
10. Patient willing and able to return for all study clinical visits and to complete all related procedures.

Exclusion criteria 25

1. Study eye aphakic with missing posterior lens capsule
2. History of focal laser located in the study eye less than 750 microns from the fovea (1/2 Papillary Diameter)
3. Ischaemic maculopathy (more than 2-fold increase in the surface area of the central avascular zone)
4. Proliferative diabetic retinopathy (presence of pre-retinal neovessels) in the study eye
5. Eye studied with an anterior chamber implant or intraocular implant with iridal or transcleral fixation or rupture of the posterior lens capsule
6. Eye studied with an ARTISAN® type lens implant
7. 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.
8. Cataract surgery on the eye studied < 3 months
9. Last session of panretinal laser photocoagulation of the study eye < 1 month
10. Last session of focal laser treatment of the posterior pole of the study eye < 1 month
11. Vitreo-macular traction syndrome associated with an epiretinal membrane in the study eye
12. History of laser treatment in the macular grid of the study eye
13. Ocular hypertension or open-angle glaucoma of the studied eye treated with at least one dual therapy.
14. Patients with systemic pathology likely to interfere with the evolution of DME and treated with immunosuppressants, systemic corticoids, anti-aldosterone, systemic anti-VEGF, etc.
15. 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.
16. Known hypersensitivity to the active substance or to one of the excipients or to anesthetic or hypotonizing eye drops.
17. 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.
18. Active or suspected infectious conjunctivitis and/or adnexal infection
19. Any ocular disease or condition of the study eye which, in the opinion of the investigator, may require intraocular surgery within 12 months
20. Contralateral eye with visual acuity < 23 letters
21. Pregnant or breast-feeding women
22. 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.
23. Patient of legal age (Code de la Santé Publique)
24. Patient currently participating in another interventional clinical trial (eye studied and/or eye not studied).
25. Follow-up not possible for 24 months, at the investigator's discretion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference between the highest value of Best Corrected Visual Acuity (BCVA) observed during follow-up to 52 weeks and the BCVA observed at inclusion (best observed improvement). Corrected visual acuity will be measured as the number of letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at an initial distance of 4 meters.

Secondary endpoints 11

1. Describe the time required to reach the highest MAVC value during the first 52 weeks, as well as the number of injections.
2. Description of VA by : oDifference between the highest value of BCVA observed up to M18 and up to M24 and the value at inclusion. Corrected VA measured on the ETDRS scale; o VA value at each visit (monthly for the 1st year) and area under the curve between inclusion and S52 and between inclusion and M24; o At S12,S24,S36,S52,M18 and M24, as well as for the highest CVAM observed in 52 weeks: proportion of patients by CVAM change category (cf protocole)
3. Total number of injections performed per patient at S52 and M24.
4. Patient discomfort related to the intravitreal implant, measured by a visual analog scale (VAS between 0 and 10) at each visit between S0 and S52.
5. At S12,S24,S36,S52,M18 and M24; as well as for the visit at which the best improvement over 52 weeks is observed: Variation in CMT and central foveolar thickness and qualitative analysis of each OCT (from a central section of the fovea: presence of interruptions of the ellipsoid, outer limiting membrane, intraretinal cysts or logettes, presence of disorganized inner retinal layers, subretinal fluid, foveolar depression, epiretinal membrane, vitreo-macular traction and macular exudates).
6. Proportion of patients with resolution of macular oedema (defined as absence of intraretinal fluid 6 months or more after the last injection) at S52 and M24.
7. At S12, S24, S36, S52, M18 and M24, the number and percentage of patients with each grade of diabetic retinopathy according to the Staging DRSS will be calculated: improvement (gain of 2 levels or gain of 3 levels), no change, or worsening (loss of 2 levels or loss of 3 levels); between inclusion and S12, S24, S36, S52, M18 and M24, according to a centralised review on colour fundus photographs including at least the 7 ETDRS fields i.e. 30 degrees.
8. At S12, S24, S36, S52, M18 and M24: qualitative and quantitative analysis of diabetic vascularisation and non-perfusion zones on OCT-angiography (size of capillary non-perfusion zones, size of central avascular zone, presence of macular ischaemia) according to a centralised reading
9. At each visit: condition of lens implant and posterior chamber determined by biomicroscopy with fundus.
10. Change in intraocular pressure between inclusion and S52, and between inclusion and M24, and proportion of patients using hypotonising therapy for 24 months.
11. Adverse events observed throughout the study: o Frequency of ocular prognostic adverse events: see protocol o Incidence of non-ocular life-threatening adverse events: see protocol o Incidence of systemic adverse events: see protocol

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Laurent Kodjikian

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Laurent Kodjikian

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications