Combination OZURDEX® & LUCENTIS® vs. OZURDEX® Monotherapy in Incomplete-Responders With Diabetic Macular Edema

NCT02684084 | Terminated Phase 4

• 1 other identifier: IIT-CAN-EYE-0399
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

This is a 24-week, prospective, multi-center, open-label, randomized, investigator-initiated pilot study to explore the effects of RBZ (0.5 mg) plus DEX implant (0.7 mg) PRN combination therapy (n = 30) vs. DEX implant PRN monotherapy (n = 30) in pseudophakic eyes with center-involved DME that have demonstrated prior incomplete response to 3-6 anti-VEGF treatments.

Conditions

Diabetic Macular Edema

Keywords

Diabetic Macular Edema; Ozurdex; Lucentis

Outcome Measures

Primary Outcomes (1)

• Comparison of mean change from baseline ETDRS BCVA letters

  Carried out using Area Under the Curve (AUC) analysis

  From randomization (0) to 24+/- 1 weeks

Secondary Outcomes (5)

• Mean change in Central Subfield Thickness (CST)

  From randomization (0) to 24+/- 1 weeks

• Number of re-injections

  From randomization (0) to 24+/- 1 weeks

• Re-injection interval

  From randomization (0) to 24+/- 1 weeks

• Proportion of eyes with 15- and 10-ETDRS letters gained/lost

  From randomization (0) to 24+/- 1 weeks

• Proportion of study eyes with Proliferative Diabetic Retinopathy (PDR) at study completion

  From randomization (0) to 24+/- 1 weeks

Study Arms (2)

Combination group (RBZ+DEX)

ACTIVE COMPARATOR

30 eyes will receive an intravitreal Lucentis (0.5 mg) injection followed by Ozurdex implant (0.7 mg) injection within 0 to 8 days.

Drug: Ozurdex; Drug: Lucentis

Monotherapy group (DEX only)

ACTIVE COMPARATOR

30 eyes will receive Ozurdex implant (0.7 mg) injection only

Drug: Ozurdex

Interventions

Ozurdex DRUG

OZURDEX® (DEX implant; Allergan Inc. Irvine, CA, USA) is a sustained-release biodegradable implant approved for treatment of Macular Edema secondary to central retinal vein occlusion as well as noninfectious uveitis affecting the posterior segment

Also known as: DEX implant, dexamethasone

Combination group (RBZ+DEX); Monotherapy group (DEX only)

Lucentis DRUG

LUCENTIS® (0.5 mg ranibizumab or RBZ, an anti-neovascular VEGF-A inhibitor, Novartis Pharmaceuticals Canada Inc.) was the first approved medical treatment for DME

Also known as: Ranibizumab

Combination group (RBZ+DEX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 1 or 2 diabetic patients
• Pseudophakic (or phakic without cataract;\<1+ nuclear sclerosis) lens status 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
• Center-involved DME \> 250 µm
• Baseline BCVA between 20/40 - 20/320
• Duration of DME ≤ 9 months
• Glycosylated haemoglobin (HbA1c) levels ≤ 11%
• Eyes with intraocular pressure (IOP) ≤ 21 and / or treatment with \< 2 topical IOP-lowering medications (eyes with history of previous angle -closure or similar conditions 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 and the patient has been and can be safely dilated)
• 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:
• \< 20% reduction in central subfield thickness (CST) by SD-OCT compared to the baseline first RBZ injection, or
• \< 5-letter increase in visual acuity compared to the baseline first RBZ injection and/or
• the opinion of the treating ophthalmologist additional anti-VEGF monotherapy is not deemed likely to provide further therapeutic benefit
• If both eyes qualify investigators may enrol bilaterally, with one eye receiving the RBZ plus DEX implant combination regimen and the other receiving the DEX implant monotherapy regimen
• Written informed patient consent

You may not qualify if:

• 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.
• Patients with known hypersensitivity to any components of RBZ or DEX implant
• Patient has suffered from a stroke or trans-ischemic attack (TIA) in the last 6 months
• Patients using topical anti-inflammatory medication for the duration of the study
• Patients with ACIOL (Anterior Chamber Intraocular Lens) and rupture of the posterior lens capsule
• Prior panretinal or macular laser treatments
• Previous vitrectomy
• Any ocular condition that in the opinion of the investigator would not permit improvement of visual acuity with resolution of ME (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates and/or poor foveal architecture suggestive of photoreceptor loss)
• Patients with retinal diseases, other than diabetes that can affect ME
• HbA1c levels \> 11%
• 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)
• Eyes with a history of steroid response (i.e., increase of ≥ 5 mmHg IOP following topical steroid treatment)
• Eyes with demonstrated response to 3-6 prior monotherapy intravitreal anti-VEGF (i.e., AVASTIN®, LUCENTIS® or EYLEA® administered every 4 ± 2 weeks over 12-36 weeks (or 3-9 months)); response is defined herein as a treatment effect resulting in:
• ≥ 20% reduction in CST by SD-OCT from baseline first anti-VEGF injection,
• ≥ 5-letter increase in visual acuity since the baseline first anti-VEGF injection and/or,

Sponsors & Collaborators

• North Toronto Eye Care Laser and Eye Specialists: lead
• Allergan: collaborator

Study Sites (2)

Toronto Retina Institue

Toronto, Ontario, M3C 0G9, Canada

Location

North Toronto Eye Care Laser and Eye Specialists

Toronto, Ontario, M3N 2V6, Canada

Location

Related Publications (24)

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MeSH Terms

Interventions

Calcium Dobesilate; Dexamethasone; Ranibizumab

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pradeepa Yoganathan, MD, MSc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 26, 2015
• First Posted: February 17, 2016
• Study Start: November 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 20, 2018

Record last verified: 2018-08

Locations

CA (2)