Diabetic Macular Edema
Conditions
Keywords
Diabetic Macular Edema (DME)
Brief summary
* To assess the safety of repeated iCo-007 intravitreal injections in treatment of subjects with diabetic macular edema as monotherapy and in combination with ranibizumab or laser photocoagulation * To assess the change in visual acuity and retinal thickness on optical coherence tomography (OCT) from baseline to month 8 and month 12
Interventions
DRUGiCo-007 350 mcg
iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4
DRUGiCo-007 700 mcg
iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4
DRUGiCo-007 350 mcg and Laser
iCo-007 (350 μg) as an intravitreal injection at baseline followed 7 days later by laser photocoagulation. At M4, intravitreal injection of iCo-007 (350 μg) will be given as mandatory treatment. If the eye also meets retreatment criteria, it will also receive the second laser photocoagulation
DRUGRanibizumab and iCo-007 350 mcg
Ranibizumab (0.5 mg) intravitreal injection at baseline followed by iCo-007 (350 μg) intravitreal injection 2 weeks later; re-treatment with ranibizumab (0.5 mg) mandatory at M4 followed by iCo-007 (350 μg) 2 weeks later
Sponsors
Juvenile Diabetes Research Foundation
iCo Therapeutics Inc.
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Have diabetes mellitus type I or II (insulin or non-insulin dependent) with HbA1c ≥5.5% and HbA1c ≤13%; have non-proliferative diabetic retinopathy, or inactive proliferative diabetic retinopathy, or proliferative diabetic retinopathy with a reasonable expectation that panretinal photocoagulation will not be required during the study follow-up period * Have diabetic macular edema with central subfield thickness of ≥250 microns (confirmed by Stratus Time-Domain(TD) OCT * Have best corrected visual acuity (ETDRS) that is Snellen equivalent of * 20/32 and ≥20/320, inclusive * Be willing and able to sign an approved written informed consent. If a patient has a central nervous system disorder (i.e. dementia) that will not allow him/her to understand the consent independently, the patient will not be allowed to join the study * Be able to attend all scheduled study visits * Women who are not lactating or pregnant and are willing to use adequate contraception during the study period, if appropriate
Exclusion criteria
* Have macular or perimacular edema secondary to an etiology other than diabetes * Have concurrent retinal diseases other than diabetic retinopathy * Have additional ocular diseases compromising visual acuity and/or interfering with study assessments; patients who have glaucoma but deemed stable (intraocular pressure ≤ 25 mmHg at screening) on medications or status post surgery, may participate in the study * Participant has a history of prior pars plana vitrectomy * Subjects with significant cataract or or posterior capsular opacification that may need intervention within one year or vitreous opacity that hinder study assessment (i.e.fundus examination) which requires intervention within a year * Subjects who have DME with severe capillary non-perfusion (avascular zone diameter \>1,000 microns) * Have an allergy to fluorescein dye * Have terminal renal disease (on active kidney dialysis), cerebral vascular accident(including TIA), myocardial infarction or congestive heart disease within 6 months of study enrollment, liver damage (2x upper limit of normal range for aspartate aminotransferase (AST), Alanine aminotransferase (ALT) or total bilirubin). Patients who may have received renal transplant in the past and now have stable renal function, may participate in the study * Subjects with systolic blood pressure higher than 180 mm Hg or diastolic above 100 mm Hg, with or without anti-hypertensive treatment * Have a history of panretinal photocoagulation (PRP) in the study eye within 3 months of study entry or are likely to have PRP in the study eye during study participation * Had macular photocoagulation or ocular surgery within 3 months of study entry in the study eye * Received intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry or anti-angiogenic drugs (pegaptanib sodium, ranibizumab, bevacizumab, VEGF-TRAP, protein kinase C inhibitor, etc.) within 2 months of study entry; history of usage of topical or systemic steroids within 3 months of study entry is not an exclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in VA From Baseline to Month 8 | Baseline to month 8 | The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Retinal Thickness Measured | Baseline to month 12 | measured by OCT |
| Duration of iCo-007 Treatment Effect | Baseline to month 12 | treatment effect as measured by VA and OCY thickness |
| Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections | Baseline to month 12 | cmax |
| Change in VA From Baseline to Month 12 | Baseline to month 12 | The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 12 |
| Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | Baseline to month 8 | Group 1 |
| Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | Baseline to month 8 | Safety of repeated iCo-007 intravitreal injections in treatment of subjects with Diabetic Macular Edema (DME) as monotherapy and in combination with ranibizumab or laser photocoagulation. Serious consideration will be given if 2 or more patients in a particular treatment arm experience the same drug-related serious adverse event; |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 iCo-007 350 mcg: iCo-007 (350 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (350 μg) at month 4 | 47 |
| Group 2 iCo-007 700 mcg: iCo-007 (700 μg) as an intravitreal injection at baseline followed by another iCo-007 dose (700 μg) at month 4 | 46 |
| Group 3 iCo-007 350 mcg Plus Laser: iCo-007 (350 μg) as an intravitreal injection at baseline followed 7 days later by laser photocoagulation. At M4, intravitreal injection of iCo-007 (350 μg) will be given as mandatory treatment. If the eye also meets retreatment criteria, it will also receive the second laser photocoagulation | 47 |
| Group 4 Ranibizumab Plus iCo-007 350 mcg: Ranibizumab (0.5 mg) intravitreal injection at baseline followed by iCo-007 (350 μg) intravitreal injection 2 weeks later; re-treatment with ranibizumab (0.5 mg) mandatory at M4 followed by iCo-007 (350 μg) 2 weeks later | 45 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 4 | 0 | 3 |
| Overall Study | Physician Decision | 2 | 5 | 0 | 0 |
| Overall Study | Rescue Therapy | 8 | 5 | 5 | 8 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 8.91 | 62.8 years STANDARD_DEVIATION 9.7 | 61.4 years STANDARD_DEVIATION 9.72 | 61.2 years STANDARD_DEVIATION 7.29 | 62.2 years STANDARD_DEVIATION 8.95 |
| Baseline Best Corrected Visual Acuity (BCVA) | 57.9 Letters STANDARD_DEVIATION 12.3 | 58.7 Letters STANDARD_DEVIATION 12.49 | 59.8 Letters STANDARD_DEVIATION 13.78 | 61.5 Letters STANDARD_DEVIATION 14.03 | 59.3 Letters STANDARD_DEVIATION 13.15 |
| Sex: Female, Male Female | 27 Participants | 19 Participants | 20 Participants | 17 Participants | 83 Participants |
| Sex: Female, Male Male | 20 Participants | 27 Participants | 27 Participants | 28 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 | 1 / 47 | 0 / 45 |
| other Total, other adverse events | 32 / 47 | 35 / 46 | 36 / 47 | 35 / 45 |
| serious Total, serious adverse events | 5 / 47 | 9 / 46 | 5 / 47 | 15 / 45 |
Outcome results
Primary
Change in VA From Baseline to Month 8
The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 8
Time frame: Baseline to month 8
Population: The results are from the participants which completed the primary end point and for which the data is available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change in VA From Baseline to Month 8 | -12.07 Letters | Standard Deviation 18.2 |
| Group 2 | Change in VA From Baseline to Month 8 | -24.46 Letters | Standard Deviation 24.02 |
| Group 3 | Change in VA From Baseline to Month 8 | -15.22 Letters | Standard Deviation 24.62 |
| Group 4 | Change in VA From Baseline to Month 8 | -18.28 Letters | Standard Deviation 30.45 |
Secondary
Change in Retinal Thickness Measured
measured by OCT
Time frame: Baseline to month 12
Population: The study was terminated prior to month 12. No data was collected and 0 participants were analyzed at month 12
Secondary
Change in Retinal Thickness Measured by OCT From Baseline to Month 8
Group 1
Time frame: Baseline to month 8
Population: Some participants opted out of the month 8 OCT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1 | Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | -70.68 microns | Standard Deviation 176.31 |
| Group 2 | Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | -160.22 microns | Standard Deviation 177.36 |
| Group 3 | Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | -54.17 microns | Standard Deviation 125.35 |
| Group 4 | Change in Retinal Thickness Measured by OCT From Baseline to Month 8 | -92.10 microns | Standard Deviation 185.49 |
Secondary
Change in VA From Baseline to Month 12
The primary efficacy variable is the change in visual acuity (mean change in number of letters) from baseline to month 12
Time frame: Baseline to month 12
Population: The study was terminated prior to month 12. No data was collected and 0 participants were analyzed at month 12
Secondary
Duration of iCo-007 Treatment Effect
treatment effect as measured by VA and OCY thickness
Time frame: Baseline to month 12
Population: The study was terminated prior to month 12. No data was collected and 0 participants were analyzed at month 12
Secondary
Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability
Safety of repeated iCo-007 intravitreal injections in treatment of subjects with Diabetic Macular Edema (DME) as monotherapy and in combination with ranibizumab or laser photocoagulation. Serious consideration will be given if 2 or more patients in a particular treatment arm experience the same drug-related serious adverse event;
Time frame: Baseline to month 8
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 | Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | 0 Participants |
| Group 2 | Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | 0 Participants |
| Group 3 | Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | 0 Participants |
| Group 4 | Number of Participants in a Given Study Arm Experiencing the Same Drug-related Serious Adverse Event as a Measure of Safety and Tolerability | 0 Participants |
Secondary
Peak Plasma Concentration (Cmax)of iCo-007 After Multiple Injections
cmax
Time frame: Baseline to month 12
Population: The study was terminated prior to month 12. No data was collected and 0 participants were analyzed at month 12