Diabetic Macular Edema, Hard Lipid Exudates
Conditions
Brief summary
This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield.
Detailed description
This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield. Consented, enrolled subjects will receive multiple open-label intravitreal injections on 0.3mg ranibizumab administered every 30 days for 12 months per the treatment algorithm. The patients will be randomized to 1 of 2 treatment groups. Group 1: Treatment algorithm based on the Diabetic Retinopathy Clinical Research (DRCR) protocol I 4:2:7 strategy based on the presence of macular edema. Group 2: Continue treatment until not only the macular edema is resolved but also until the lipid exudate is resolved. Sample size: 30 eyes Follow-up Schedule: Every 4 weeks throughout the study.
Interventions
DRUGranibizumab 0.3mg
intravitreally administered
Sponsors
Genentech, Inc.
Doheny Image Reading Center
The Retina Partners
South Coast Retina Center; Carson, McBeath, Boswell, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Subjects will be eligible if the following criteria are met: Inclusion Criteria * Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age ≥ 18 years * Type 1 or Type 2 Diabetes mellitus * Best corrected ETDRS visual acuity (20/32-20/320) or letter score 78 to 24 * Diabetic macular edema on clinical examination involving the center of the macula assessed to be the main cause of visual loss * Retinal thickness measured on spectral domain optical coherence tomography (OCT). Zeiss Cirrus: ≥290μm in women and ≥305 μm in men in the central subfield. Heidelberg Spectralis: ≥305μm in women and ≥320 μm in men in the central subfield * Lipid exudates involving the central subfield on spectral domain OCT.
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from this study: * Treatment for diabetic macular edema within the prior 4 months. * Panretinal photocoagulation within the prior 4 months or anticipated need for panretinal photocoagulation within the next 6 months * major ocular surgery within the prior 4 months * myocardial infarction, other cardiac event requiring hospitalization, cerebrovascular accident, transient ischemic attack, or treatment for acute congestive heart failure occurred within 4 months before randomization * Pregnancy (positive pregnancy test) or lactation * Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch. * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated * Participation in another simultaneous medical investigation or trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | 6-12 months | Compare Group 1 and Group 2 for best correct visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 12 months |
| Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography | 12 months |
| Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 12 months |
| Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 12 months |
| Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 12 months |
| Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability | 12 months |
| Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability | 12 months |
| Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema.
ranibizumab 0.3mg: intravitreally administered | 12 |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved.
ranibizumab 0.3mg: intravitreally administered | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Total | Diabetic Macular Edema Treatment Group (Group 1) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 9 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 15 Participants | 8 Participants |
| Age, Continuous | 67 years STANDARD_DEVIATION 8.83 | 65.75 years STANDARD_DEVIATION 8.65 | 64.5 years STANDARD_DEVIATION 8.46 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 12 participants | 24 participants | 12 participants |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 9 / 12 | 9 / 12 |
| serious Total, serious adverse events | 3 / 12 | 2 / 12 |
Outcome results
Primary
Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months
Compare Group 1 and Group 2 for best correct visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters.
Time frame: 6-12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | 6 Months | 78 letters read correctly | Standard Deviation 9.98 |
| Diabetic Macular Edema Treatment Group (Group 1) | Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | 12 Months | 77.92 letters read correctly | Standard Deviation 9.61 |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | 12 Months | 74.83 letters read correctly | Standard Deviation 8.32 |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | 6 Months | 73.92 letters read correctly | Standard Deviation 8.4 |
Secondary
Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability
Time frame: 12 months
Population: eyes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability | 0 Participants |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability | 4 Participants |
Secondary
Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability
Time frame: 12 months
Population: eyes
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability | 9 Participants |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability | 9 Participants |
Secondary
Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography | 7 eyes |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography | 7 eyes |
Secondary
Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 0 eyes |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 0 eyes |
Secondary
Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 60 percentage of eyes |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 58 percentage of eyes |
Secondary
Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 90 percentage of eyes |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography | 92 percentage of eyes |
Secondary
Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 70 percentage of eyes |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography | 83 percentage of eyes |
Secondary
Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diabetic Macular Edema Treatment Group (Group 1) | Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography | 0 participants |
| Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography | 0 participants |