A clinical study of OPT-302 with aflibercept compared to aflibercept plus sham in patients with diabetic macular edema

Phase 1

• Conditions: Persistent central-involved diabetic macular edema; MedDRA version: 20.0Level: SOCClassification code 10015919Term: Eye disordersSystem Organ Class: 10015919 - Eye disorders; MedDRA version: 20.1Level: LLTClassification code 10057934Term: Diabetic macular edemaSystem Organ Class: 10015919 - Eye disorders; Therapeutic area: Diseases [C] - Eye Diseases [C11]

• Registration Number: EUCTR2018-003298-90-LV
• Lead Sponsor: Opthea Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-09
• Last Update Posted: 21 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

STUDY EYE
1)Able and willing to provide written informed consent
2)Age = 18 years of either gender
3)Diabetes mellitus (type 1 or type 2)
4)Edema that involves the center of the macula as confirmed by the reading center
5)Eyes with recurrent / persistent DME despite prior intravitreal anti-VEGF therapy with a suboptimal response and defined as meeting all of the following:
a.Ophthalmoscopic evidence of center-involved DME
b.Retinal thickness = 320 µm in the central 1 mm subfield on Spectralis (Heidelberg) SD-OCT (or = 305 µm on Cirrus) as confirmed by the reading center
c.DME is the cause of OCT thickening despite ongoing treatment with either aflibercept or ranibizumab with = 3 prior IVT injections within 5 months of study Day 1, the most recent injection being = 42 days prior to study Day 1 (prior bevacizumab allowed only if therapy subsequently switched to intravitreal aflibercept or ranibizumab for = 1 most recent injection(s) prior to study Day 1)
6)History of center-involved macular edema requiring treatment, including intravitreal antVEGF-A therapy, for = 24 months (maximum number of intravitreal anti-VEGF-A injection cycles is = 24)
7)BCVA letter score = 73 and = 24 (approximate Snellen equivalent 20/40 to 20/320; Snellen [metric] equivalent 6/12 to 6/96) in the study eye, inclusive
8)If female and of child-bearing potential: Pregnancy test at screening and Day 1 is negative, and agrees to use a highly effective method of contraceptive for the duration of the study and for at least 3 months following the last dose of study medication. The following are considered highly effective methods”: i.e. hormonal contraceptive (oral, intravaginal, or implant, but excluding progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of action); intrauterine device; or documented vasectomy of partner. A participant will not be considered to be of child-bearing potential if she is postmenopausal and has not had menses for at least 12 months prior to screening (by history), or if surgically sterile
9)Only one eye will be enrolled in the study. (If both eyes meet the entry criteria the study eye chosen is the worse eye (based on investigator assessment of SD-OCT and / or VA). If both eyes are equal, the participant and investigator will select the eye for entry).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38

Exclusion Criteria

1)Eyes in which scatter PRP is needed now or within the next 3 months (e.g. eyes with high risk PDR [defined as NVD> 1/3 disc area or NVE > 1/2 disc area and presence of VH regardless of size of neovascularization] not already adequately treated with photocoagulation)
2)Macula edema is due to a cause other than DME in the study eye (e.g. clinical exam by investigator and OCT as confirmed by the reading center suggest that vitreoretinal interface abnormalities such as taut posterior hyaloid or ERM are the primary cause of macular edema)
3)Presence of any abnormality that in the opinion of the investigator would be likely to confound assessment of VA improvement in the study eye in which macular edema resolves, or improves, such as dense subfoveal hard exudates, NVG, or presence of chorioretinal / foveal atrophy involving the center of the macula
4 )Vitreoretinal traction confirmed by OCT, or seen clinically within 1 disc diameter of the center of the macula of the study eye as confirmed by the reading center
5)Any RVO involving the macula in the study eye as confirmed by the reading center
6 )Any intraocular surgery in the study eye within 4 months of study entry or within the next 3 months following dosing on Day 1
7)Previous vitrectomy or SB surgery in the study eye
8)HbA1C level =12% and/or recent signs of uncontrolled diabetes (3 or more episodes of severe hypoglycemia within 3 months of baseline, or hospitalization for hyperglycemia, or 2 or more episodes of ketoacidosis within 1 year of baseline, or an episode of ketoacidosis within 3 months of baseline).
9)Renal failure, dialysis, or history of renal transplant
10)Myocardial infarction, other cardiac event requiring hospitalization, stroke, TIA, or treatment for CHF within 6 months prior study Day 1.
11)Uncontrolled hypertension =180 mmHg systolic or =110 mmHg diastolic. (If blood pressure is brought below 180/110 mmHg by anti-hypertensive treatment, the individual can become eligible. Participants with a history of controlled hypertension on medication may have their blood pressure taken at a second visit to qualify based on the repeat testing).
12)Pregnant or lactating
13)Major surgery (defined as intra-abdominal or surgery requiring general anesthesia) within 28 days prior to dosing on study Day 1 or major surgery planned during the next 6 months.
14)Previous treatment with PDT or external beam radiation in the study eye
15)Subjects who have received panretinal or focal / grid photocoagulation, YAG laser, or peripheral retinal cryoablation (for retinal tears only) in the study eye within the previous 4 months
16)Parallel or prior use of systemic anti-VEGF agents
17)Parallel or prior use of intravitreal bevacizumab in the study eye, unless therapy switched to intravitreal aflibercept or ranibizumab for = 1 most recent injection(s) prior to Day 1
18)Most recent intravitreal injection of aflibercept or ranibizumab less than 28 days or greater than or equal to 42 days prior to Day 1 dosing in the study eye
19)Administration of systemic steroids within 4 months prior to Day 1
20)Parallel or prior use of any intravitreal injections of steroids within 4 months prior to Day 1 in the study eye
21)Parallel or prior use of dexamethasone implant in the study eye
22)Parallel or prior use of fluocinolone implant in the study eye
23)Parallel or prior administration of experimental therapy within 30 days of screening
24)Parallel treatment for active systemic (non-o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified