Diabetic Macular Edema
Conditions
Brief summary
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
Detailed description
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).
Interventions
DRUGLuminate 1.0mg
DRUGLuminate 2.0mg
DRUGLuminate 3.0mg
DRUGAvastin
DRUGLuminate 0.5mg
Sponsors
Trial Runners, LLC
Duke University
Allegro Ophthalmics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in BCVA at Week 24 | Value of 24 Weeks minus baseline value | Primary efficacy outcome is BCVA changes at Week 24 as compared to baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Luminate 1.0mg Group Stage 1- Luminate 1.0 mg intravitreal injection administered at baseline (Day 0), 4 weeks and 8 weeks with prn Luminate injection at week 20 for a total of at least 3 and no more than 4 Luminate injections. Sham injections will be performed at weeks 12 and 16 and may also be performed at week 20 if prn Luminate is not required; sham laser treatment will be administered at baseline and at 16 weeks.
Luminate 1.0mg | 39 |
| Luminate 2.0mg Group Stage 1 -Luminate 2.0 mg intravitreal injection administered at baseline (Day 0), 4 weeks and 8 weeks with prn Luminate injection at week 20 for a total of at least 3 and no more than 4 Luminate injections. Sham injections will be performed at weeks 12 and 16 and may also be performed at week 20 if prn Luminate is not required; sham laser treatment will be administered at baseline and at 16 weeks.
Luminate 2.0mg | 33 |
| Luminate 3.0mg Group Stage 1- Luminate 3.0 mg intravitreal injection administered at baseline (Day 0), 4 weeks and 8 weeks with prn Luminate injection at week20 for a total of at least 3 and no more than 4 Luminate injections. Sham injections will be performed at weeks 12 and 16 and may also be performed at week 20 if prn Luminate is not required; sham laser treatment will be administered at baseline and at 16 weeks.
Luminate 3.0mg | 42 |
| Avastin® Group Stage 1- Avastin 1.25 mg intravitreal injection administered at baseline (Day 0), 4 weeks and 8 weeks with prn Avastin injection at weeks 12, 16, or 20 for a total of at least 3 and up to 6 Avastin injections. Sham injections may be performed at weeks 12, 16, and 20 if prn Avastin is not required.
Avastin | 24 |
| Avastin Then Luminate 1.0 mg IVT + Sham Injection Stage 2 - Week 0 (Baseline): Avastin 1.25 mg IVT Weeks 1, 4 and 8: Luminate 1.0 mg IVT + sham injection Weeks 12 and 16: Sham IVT
Luminate 1.0mg
Avastin | 19 |
| Avastin Then Luminate 0.5 mg IVT + Sham Injection Stage 2- Week 0 (Baseline); Avastin 1.25 mg IVT Weeks 1, 4 and 8: Luminate 0.5 mg IVT + sham injection Weeks 12 and 16: Sham IVT
Avastin
Luminate 0.5mg | 17 |
| Sham Then Luminate 1.0 mg + Avastin 1.25 mg IVT Stage 2 : Week 0 (Baseline): Sham IVT Weeks 1, 4 and 8: Luminate 1.0 mg + Avastin 1.25 mg IVT Weeks 12 and 16: Sham IVT
Luminate 1.0mg
Avastin | 13 |
| Sham Then Luminate 0.5 mg IVT + Avastin 1.25 mg IVT Stage 2 : Week 0: Sham IVT Weeks 1, 4 and 8: Luminate 0.5 mg IVT + Avastin 1.25 mg IVT Weeks 12 and 16: Sham IVT
Avastin
Luminate 0.5mg | 16 |
| Avastin 1.25 mg + Sham IVT Stage 2 : Week 0 (Baseline): Sham IVT Weeks 1, 4 and 8: Avastin 1.25 mg + Sham IVT Weeks 12 and 16: Avastin PRN
Luminate 0.5mg | 15 |
| Total | 218 |
Baseline characteristics
| Characteristic | Luminate 1.0mg Group | Luminate 2.0mg Group | Luminate 3.0mg Group | Avastin® Group | Avastin Then Luminate 1.0 mg IVT + Sham Injection | Avastin Then Luminate 0.5 mg IVT + Sham Injection | Sham Then Luminate 1.0 mg + Avastin 1.25 mg IVT | Sham Then Luminate 0.5 mg IVT + Avastin 1.25 mg IVT | Avastin 1.25 mg + Sham IVT | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 14 Participants | 13 Participants | 9 Participants | 9 Participants | 7 Participants | 3 Participants | 4 Participants | 6 Participants | 83 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 19 Participants | 29 Participants | 15 Participants | 10 Participants | 10 Participants | 10 Participants | 12 Participants | 9 Participants | 135 Participants |
| Age, Continuous | 62.9 years STANDARD_DEVIATION 9.05 | 61 years STANDARD_DEVIATION 9.91 | 63.8 years STANDARD_DEVIATION 9.45 | 60.3 years STANDARD_DEVIATION 8.83 | 67.1 years STANDARD_DEVIATION 10.47 | 65.5 years STANDARD_DEVIATION 9.41 | 60.1 years STANDARD_DEVIATION 10.92 | 60.5 years STANDARD_DEVIATION 8.29 | 62.1 years STANDARD_DEVIATION 9.35 | 62.3 years STANDARD_DEVIATION 9.35 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 21 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized white | 33 Participants | 29 Participants | 38 Participants | 17 Participants | 17 Participants | 15 Participants | 7 Participants | 13 Participants | 12 Participants | 181 Participants |
| Region of Enrollment United States | 39 Participants | 33 Participants | 42 Participants | 24 Participants | 19 Participants | 17 Participants | 13 Participants | 16 Participants | 15 Participants | 218 Participants |
| Sex: Female, Male Female | 23 Participants | 13 Participants | 17 Participants | 6 Participants | 10 Participants | 12 Participants | 7 Participants | 8 Participants | 10 Participants | 106 Participants |
| Sex: Female, Male Male | 16 Participants | 20 Participants | 25 Participants | 18 Participants | 9 Participants | 5 Participants | 6 Participants | 8 Participants | 5 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 39 | 0 / 33 | 1 / 42 | 1 / 24 | 0 / 19 | 0 / 17 | 0 / 13 | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 28 / 39 | 20 / 33 | 25 / 42 | 16 / 24 | 10 / 19 | 5 / 17 | 6 / 13 | 7 / 16 | 3 / 15 |
| serious Total, serious adverse events | 8 / 39 | 3 / 33 | 6 / 42 | 3 / 24 | 2 / 19 | 1 / 17 | 1 / 13 | 2 / 16 | 3 / 15 |
Outcome results
Primary
Change in BCVA at Week 24
Primary efficacy outcome is BCVA changes at Week 24 as compared to baseline
Time frame: Value of 24 Weeks minus baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luminate 1.0mg Group | Change in BCVA at Week 24 | 5.2 Letters on ETDRS eye chart | Standard Error 3 |
| Luminate 2.0mg Group | Change in BCVA at Week 24 | 2.7 Letters on ETDRS eye chart | Standard Error 3 |
| Luminate 3.0mg Group | Change in BCVA at Week 24 | -1.5 Letters on ETDRS eye chart | Standard Error 3 |
| Avastin® Group | Change in BCVA at Week 24 | 7 Letters on ETDRS eye chart | Standard Error 3 |
| Avastin Then Luminate 1.0 mg IVT + Sham Injection | Change in BCVA at Week 24 | 7.1 Letters on ETDRS eye chart | Standard Error 3 |
| Avastin Then Luminate 0.5 mg IVT + Sham Injection | Change in BCVA at Week 24 | 4.6 Letters on ETDRS eye chart | Standard Error 3 |
| Sham Then Luminate 1.0 mg + Avastin 1.25 mg IVT | Change in BCVA at Week 24 | 1.4 Letters on ETDRS eye chart | Standard Error 3 |
| Sham Then Luminate 0.5 mg IVT + Avastin 1.25 mg IVT | Change in BCVA at Week 24 | 3.9 Letters on ETDRS eye chart | Standard Error 3 |
| Avastin 1.25 mg + Sham IVT | Change in BCVA at Week 24 | 6.7 Letters on ETDRS eye chart | Standard Error 3 |