Combination OZURDEX® & EyLea® vs. OZURDEX® Monotherapy in IncompLete-Responders wIth Diabetic Macular Edema

• Status: Withdrawn
• Trial end date: 2021-05-01
• Target enrollment: 0
• Participant gender: All

Summary

COLLIDE is a multi-center, open-label, 1:1 randomized study looking at the effects of aflibercept (AFL; 2.0mg) plus OZURDEX (DEX; 0.7mg) implant combination therapy versus DEX monotherapy in phakic or pseudophakic eyes with center-involved DME that have demonstrated prior incomplete response to 3-6 anti-VEGF treatment in 3-9 months. The primary outcome will be 24 week central subfield thickness. Secondary outcomes include the change in ETDRS BCVA letters, number of re-injections and re-injection interval, proportion of eyes with 15- and 10- ETDRS letter gained/lost, proportion of eyes with PDR as per Optos color and FA at the study completion (24+/- 2 weeks) and OCT and OCT angiography biomarkers.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pradeepa Yoganathan
• Collaborators: St. Michael's Hospital, Toronto; Unity Health Toronto
• Treatments: BB 1101; Dexamethasone; Dexamethasone acetate

Criteria

Inclusion Criteria:

1. Type 1 or 2 diabetic adult (≥18 years) patients

2. Known glycosylated haemoglobin (HbA1c) levels ≤ 11%

3. Screening Snellen Va / Baseline ETDRS BCVA between 20/20 - 20/320

4. Lens status: Phakic without significant cataract; <1+ nuclear sclerosis and <1+ posterior subcapsular or pseudophakic with intact posterior lens capsule and / or Nd:YAG laser capsulotomy that in the investigator's opinion is not likely to permit dislocation of DEX implant into the anterior chamber

5. Center-involved DME > 250 µm

6. Duration of DME ≤ 2 years

7. Eyes with intraocular pressure (IOP) ≤ 21 with or without treatment with < 2 topical IOP-lowering medications

8. Eyes with history of previous angle closure that have been successfully treated with either laser or surgical intervention are allowed as long as the visual fields and optic nerves have been stable for > 1 year prior to study entry

9. Demonstrated incomplete response to 3-6 prior intravitreal anti-VEGFs (AVASTIN®, LUCENTIS®, or EYLEA®; administered every 4 ± 2 weeks over 12-36 weeks (or 3-9 months)); incomplete response is defined herein as a treatment effect resulting in:

1. < 25% reduction in central subfield thickness (CST) by SD-OCT during two recent visits OR

2. < 10-letter (2 lines) increase in visual acuity compared to the baseline first anti-VEGF injection

10. If both eyes qualify, investigators can enrol the eye that has developed DME most recently.

11. Written informed patient consent

Exclusion Criteria:

1. Prior panretinal or macular laser treatments

2. Any Intravitreal injection prior to run-in phase

3. Previous vitrectomy

4. Any ocular condition that in the opinion of the investigator would not permit improvement of visual acuity with resolution of ME (e.g., epiretinal membrane, foveal atrophy, known macular ischemia, pigment abnormalities, dense subfoveal hard exudates and/or poor foveal architecture suggestive of photoreceptor loss)

5. Patients with retinal diseases, other than diabetes that can affect ME

6. HbA1c levels > 11%

7. Patient has suffered from a stroke in the last 3 months

8. Eyes with a history of advanced glaucoma (optic nerve head change consistent with glaucoma damage and / or glaucomatous visual field loss), uncontrolled ocular hypertension (baseline IOP > 21 mmHg despite use of ≥ 2 topical IOP-lowering medication)

9. Eyes with a history of steroid response (i.e., increase of ≥ 5 mmHg IOP following topical steroid treatment)

10. Patients with ACIOL (Anterior Chamber Intraocular Lens) or rupture of the posterior lens capsule that in the investigator's opinion is likely to permit dislocation of DEX implant into the anterior chamber

11. Female patients who are pregnant or breast feeding: all women of child bearing potential (i.e. women who are not surgically sterile or who have had one or more menstrual cycle in the previous 12 months) must have a negative pregnancy test prior to randomization, and must agree to use appropriate measures to avoid pregnancy during the trial period.

12. Patients who are unable to attend scheduled follow-up visits throughout the 24-week study

13. Use of systemic steroid, systemic anti-VEGF or pro-VEGF treatment within 4 months prior to enrolment or anticipated use during the study (these drugs are prohibited from use during the study)

14. Patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

15. Patients with known hypersensitivity to any components of anti-VEGF or DEX implant

16. Patients using topical anti-inflammatory medication for the duration of the study