E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema |
Diabetic Macular Edema |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate high dose and low dose Sustained release Fluocinolone Acetonide Insert in the management of patients with Diabetic Macular Edema |
To evaluate high dose and low dose Sustained release Fluocinolone Acetonide Insert in the management of patients with Diabetic Macular Edema |
|
E.2.2 | Secondary objectives of the trial |
1. To chose the optimum dose level for intravitreal fluocinolone acetonide
2. To compare the two dose levels versus the control group at other timepoints
3. To evaluate the safety and efficacy of ASI-001A and ASI-001B in DME and diabetic retinopathy using the relevant measures |
1.To chose the optimum dose level for intravitreal fluocinolone acetonide
2.To compare the two dose levels versus the control group at other timepoints
3.To evaluate the safety and efficacy of ASI-001A and ASI-001B in DME and diabetic retinopathy using the relevant measures |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males and non-pregnant females at least 18 years of age
BCVA of ≥19 and ≤68 letters in the study eye by an ETDRS chart.
BCVA of the non-study eye must be no worse than 20/400
Diagnosis of diabetes mellitus (type 1 or type 2):
o Use of insulin for the treatment of diabetes for at least the 3 months prior to screening
o Use of oral ant hyperglycemia agents for the treatment of diabetes for at least the 3 months prior to screening
DME based on investigator's clinical evaluation and demonstrated on funds photographs, fluorescein angiograms, and optical coherence tomography (OCT)
Mean foveal thickness of at least 250 µm by OCT
Ability and willingness to comply with the treatment and follow up procedures
Ability to understand and sign the Informed Consent Form.
At least one macular laser treatment more than 12 weeks prior to the screening visit |
Males and non-pregnant females at least 18 years of age
BCVA of ≥19 and ≤68 letters in the study eye by an ETDRS chart.
BCVA of the non-study eye must be no worse than 20/400
Diagnosis of diabetes mellitus (type 1 or type 2):
o Use of insulin for the treatment of diabetes for at least the 3 months prior to screening
o Use of oral ant hyperglycemia agents for the treatment of diabetes for at least the 3 months prior to screening
DME based on investigator's clinical evaluation and demonstrated on funds photographs, fluorescein angiograms, and optical coherence tomography (OCT)
Mean foveal thickness of at least 250 µm by OCT
Ability and willingness to comply with the treatment and follow up procedures
Ability to understand and sign the Informed Consent Form.
At least one macular laser treatment more than 12 weeks prior to the screening visit |
|
E.4 | Principal exclusion criteria |
Pregnant, lactating females or females of childbearing potential (unless using reliable contraception, i.e. double barrier, surgical sterilization, oral contraceptives, Norplant, intrauterine device (IUD)
Laser treatment for DME within 12 weeks of screening or judged to be necessary within 6 weeks following enrollment
Any ocular surgery in the study eye within 12 weeks of screening
Yag capsulotomy in the study eye within 15 days of screening
Prior intravitreal, subtenon, or periocular steroid therapy within 3 months prior to enrollment (e.g., triamcinolone) or prior treatment with intravitreal anti-VEGF treatment within 2 months of enrollment (Lucentis, Avastin, Macugen.) Systemic treatment with Avastin is also not allowed within 3 months prior to screening.
Any change in systemic steroidal therapy within 3 months of screening
Glaucoma, ocular hypertension, intraocular pressure (IOP) > 21 mmHg or concurrent therapy at screening with IOP-lowering agents in the study eye
Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy (e.g., presumed ocular histoplasmosis, high myopia (spherical equivalent > 8 diopters), macular degeneration)
Any active viral, fungal or bacterial disease of the cornea or conjunctiva or any history of a potentially recurrent infection which could be activated by treatment with a steroid, (e.g., ocular herpes simplex virus).
Known or suspected hypersensitivity to any of the ingredients of the investigational product or to other corticosteroids
History of vitrectomy in the study eye
History of uncontrolled IOP elevation with steroid use that did not respond to topical therapy
History or presence of any disease or condition (malignancy) that in the investigator's opinion would preclude study treatment or follow-up
Any lens opacity which impairs visualization of the posterior pole or significantly impairs vision, in the opinion of the investigator.
Peripheral retinal detachment in prospective area of insertion
Participation in another clinical trial within 12 weeks before the screening visit or during the study
Resting Systolic blood pressure at the screening visit of greater than 180 or diastolic blood pressure greater than 105. |
Pregnant, lactating females or females of childbearing potential (unless using reliable contraception, i.e. double barrier, surgical sterilization, oral contraceptives, Norplant, intrauterine device (IUD)
Laser treatment for DME within 12 weeks of screening or judged to be necessary within 6 weeks following enrollment
Any ocular surgery in the study eye within 12 weeks of screening
Yag capsulotomy in the study eye within 15 days of screening
Prior intravitreal, subtenon, or periocular steroid therapy within 3 months prior to enrollment (e.g., triamcinolone) or prior treatment with intravitreal anti-VEGF treatment within 2 months of enrollment (Lucentis, Avastin, Macugen.) Systemic treatment with Avastin is also not allowed within 3 months prior to screening.
Any change in systemic steroidal therapy within 3 months of screening
Glaucoma, ocular hypertension, intraocular pressure (IOP) > 21 mmHg or concurrent therapy at screening with IOP-lowering agents in the study eye
Retinal or choroidal neovascularization due to ocular conditions other than diabetic retinopathy (e.g., presumed ocular histoplasmosis, high myopia (spherical equivalent > 8 diopters), macular degeneration)
Any active viral, fungal or bacterial disease of the cornea or conjunctiva or any history of a potentially recurrent infection which could be activated by treatment with a steroid, (e.g., ocular herpes simplex virus).
Known or suspected hypersensitivity to any of the ingredients of the investigational product or to other corticosteroids
History of vitrectomy in the study eye
History of uncontrolled IOP elevation with steroid use that did not respond to topical therapy
History or presence of any disease or condition (malignancy) that in the investigator's opinion would preclude study treatment or follow-up
Any lens opacity which impairs visualization of the posterior pole or significantly impairs vision, in the opinion of the investigator.
Peripheral retinal detachment in prospective area of insertion
Participation in another clinical trial within 12 weeks before the screening visit or during the study
Resting Systolic blood pressure at the screening visit of greater than 180 or diastolic blood pressure greater than 105. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects who have an increase from baseline of ≥15 letters in VA score assessed at Month 24 as the primary endpoint.
There will be two secondary efficacy variables defined at Month 24:
Mean change from baseline in best corrected VA letter score as assessed by ETDRS eye chart.
Proportion of subjects with a ≥2 step worsening in the study eye compared to baseline in the ETDRS Multi-Step Eye Scale of Diabetic Retinopathy. |
Proportion of subjects who have an increase from baseline of ≥15 letters in VA score assessed at Month 24 as the primary endpoint.
There will be two secondary efficacy variables defined at Month 24:
Mean change from baseline in best corrected VA letter score as assessed by ETDRS eye chart.
Proportion of subjects with a ≥2 step worsening in the study eye compared to baseline in the ETDRS Multi-Step Eye Scale of Diabetic Retinopathy. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 50 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 52 |
E.8.9.2 | In all countries concerned by the trial days | 0 |