Phase 2 Randomized Clinical Trial of Luminate® as Compared to Avastin® in the Treatment of Diabetic Macular Edema

A Phase 2 Multi center, Randomized, Controlled, Double-Masked Clinical Trial Designed To Evaluate The Safety And Exploratory Efficacy Of Luminate® (Alg-1001) As Compared To Avastin® In The Treatment Of Diabetic Macular Edema

To evaluate the safety and efficacy of Luminate® (ALG-1001) as compared to Avastin® in patients with diabetic macular edema

- Stage 1: 120 eligible subjects with DME will be enrolled and randomized to one of 4 treatment groups at an allocation ratio of 1:1:1:1, i.e., one of three doses (1.0 mg, 2.0 mg and 3.0 mg) of Luminate intravitreal injection or Avastin intravitreal injection. Subjects will be followed monthly for 24 weeks (6 months).

Stage 2 (select sites): 75 eligible subjects with DME will be enrolled and randomized to one of 5 treatment groups at an allocation ratio of 1:1:1:1:1; i.e., one of 2 doses of Luminate intravitreal injection or Avastin intravitreal injection (0.5 mg and 1.0 mg). Subjects will be followed monthly for 20 weeks (5 months).

Eligibility Criteria:
Inclusion Criteria:

* Male or female, 18 years of age or older.
* Study eye with clinically significant diabetic macular edema (DME) with central subfield thickness ≥ 350µm on spectral domain OCT
* Best corrected visual acuity (BCVA) of 20/50 to 20/320 ETDRS equivalent (65 letters to 23 letters) in the study eye, with BCVA decrement primarily attributable to DME.
* Treatment naïve, i.e., no previous anti-VEGF treatment in the study eye or no anti-VEGF treatment in the 45 days prior to study enrollment.
* In the investigator's opinion, the subject still has significant intraretinal fluid with room for improvement in both macular edema and BCVA.
* Intra-Ocular Pressure (IOP) is under control (i.e., IOP

  ≤ 25 mm in the study eye) and study eye is not receiving any IOP lowering drops.
* Willing and able to return for all study visits.
* Able to meet the extensive post-op evaluation regimen.
* Understands and signs the informed consent form.

Exclusion Criteria:

* Active proliferative diabetic retinopathy (PDR) in the study eye such as NVE, NVD, vitreous hemorrhage, or neovascular glaucoma.
* Uncontrolled hypertension defined as systolic \>180 mmHg or \> 160 mmHg on 2 consecutive measurements or diastolic \> 100 mmHg on optimal medical regimen
* Screening HgA1c blood test \> 10.0
* Focal laser photocoagulation or intravitreal/periocular steroids of any type in the study eye within the last 90 days prior to study enrollment.
* A history of intravitreal anti-VEGF injection of any type in the study eye within the last 45 days prior to study enrollment.
* History of rhegmatogenous retinal detachment, retinal tear(s), or traction retinal detachments in the study eye.
* Epiretinal membrane and/or vitreomacular traction in the study eye as determined by the central reading center.
* Previous pars plana vitrectomy in the study eye
* Any intraocular surgery in the study eye within the last 90 days prior to study enrollment.
* YAG laser treatment in the study eye in last 30 days prior to study enrollment.
* High myopia in the study eye, with a spherical equivalent of \>8.00D at screening
* Other ocular pathologies that in the investigator's opinion would interfere with the subject's vision in the study eye.
* Chronic or recurrent uveitis.
* Ongoing ocular infection or inflammation in either eye.
* A history of cataract surgery complications/vitreous loss in the study eye.
* Congenital eye malformations in the study eye.
* A history of penetrating ocular trauma in the study eye.
* Mentally handicapped.
* Pregnant female, as determined for women less than 60 years old by a positive urine pregnancy test during the screening window.
* Nursing female.
* Currently participating in any other clinical research study.
* Contraindication to the study medication.