The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: 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. |
Drug: ranibizumab 0.3mg
intravitreally administered
Other Names:
|
Active Comparator: 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. |
Drug: ranibizumab 0.3mg
intravitreally administered
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography [12 months]
- 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 Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid 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]
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | South Coast Retina Center; Carson, McBeath, Boswell, Inc | Huntington Beach | California | United States | 92647 |
2 | South Coast Retina Center; Carson, McBeath, and Boswell, Inc | Long Beach | California | United States | 90505 |
3 | Retina Partners | Santa Monica | California | United States | 90404 |
4 | South Coast Retina Center; Carson, McBeath, Boswell, Inc | Torrance | California | United States | 90505 |
Sponsors and Collaborators
- South Coast Retina Center; Carson, McBeath, Boswell, Inc.
- Genentech, Inc.
- Doheny Image Reading Center
- Retina Partners
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- ML259577
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Period Title: Overall Study | ||
STARTED | 13 | 12 |
COMPLETED | 12 | 12 |
NOT COMPLETED | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | Total |
---|---|---|---|
Arm/Group Description | 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 | 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 | Total of all reporting groups |
Overall Participants | 12 | 12 | 24 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
8
66.7%
|
7
58.3%
|
15
62.5%
|
>=65 years |
4
33.3%
|
5
41.7%
|
9
37.5%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
64.5
(8.46)
|
67
(8.83)
|
65.75
(8.65)
|
Sex: Female, Male (Count of Participants) | |||
Female |
6
50%
|
8
66.7%
|
14
58.3%
|
Male |
6
50%
|
4
33.3%
|
10
41.7%
|
Race and Ethnicity Not Collected (Count of Participants) | |||
Count of Participants [Participants] |
0
0%
|
||
Region of Enrollment (participants) [Number] | |||
United States |
12
100%
|
12
100%
|
24
100%
|
Outcome Measures
Title | Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure Eyes | 12 | 12 |
6 Months |
78
(9.98)
|
73.92
(8.40)
|
12 Months |
77.92
(9.61)
|
74.83
(8.32)
|
Title | Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure eyes | 12 | 12 |
Number [percentage of eyes] |
70
|
83
|
Title | Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure eyes | 12 | 12 |
Number [percentage of eyes] |
60
|
58
|
Title | Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure eyes | 12 | 12 |
Number [eyes] |
7
|
7
|
Title | Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure eyes | 12 | 12 |
Number [percentage of eyes] |
90
|
92
|
Title | Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Number [participants] |
0
0%
|
0
0%
|
Title | Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Measure eyes | 12 | 12 |
Number [eyes] |
0
|
0
|
Title | Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
eyes |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Count of Participants [Participants] |
0
0%
|
4
33.3%
|
Title | Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability |
---|---|
Description | |
Time Frame | 12 months |
Outcome Measure Data
Analysis Population Description |
---|
eyes |
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 12 | 12 |
Count of Participants [Participants] |
9
75%
|
9
75%
|
Adverse Events
Time Frame | 1 year | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | ||
Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/12 (0%) | 0/12 (0%) | ||
Serious Adverse Events |
||||
Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/12 (25%) | 2/12 (16.7%) | ||
Cardiac disorders | ||||
Low Hemoglobin | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Congestive Heart Failure | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Heart Attack | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Gastrointestinal disorders | ||||
Cysticercosis | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Infections and infestations | ||||
Kidney Infection | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Appendix Surgery | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 |
Vascular disorders | ||||
Stroke | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Diabetic Macular Edema Treatment Group (Group 1) | Diabetic Macular Edema and Lipid Treatment Group (Group 2) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/12 (75%) | 9/12 (75%) | ||
Blood and lymphatic system disorders | ||||
Elevated Blood Pressure | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 |
Elevated Triglycerides | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Ear and labyrinth disorders | ||||
Ear Infection | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Ear Infection | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Eye disorders | ||||
Branch Retinal Artery Occlusion | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Central Retinal Vein Occlusion | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Ocular Hypertension | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Allergic conjunctivitis | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Subconjunctival Hemhorrage | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Visual Acuity Loss | 1/12 (8.3%) | 1 | 1/12 (8.3%) | 1 |
Floater | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Gastrointestinal disorders | ||||
Nausea/Vomiting | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 |
Immune system disorders | ||||
Shingles | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Infections and infestations | ||||
Influenza | 0/12 (0%) | 0 | 3/12 (25%) | 3 |
Sinusitis | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Metastatic Tumor | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Product Issues | ||||
Drug Administration Error | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Renal and urinary disorders | ||||
Decreased Liver Function | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 |
Social circumstances | ||||
Broken Wrist | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Right Hip Injury | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Vascular disorders | ||||
Headache | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Julie Gasperini |
---|---|
Organization | South Coast Retina Center |
Phone | 5629847024 |
jgasperini@gmail.com |
- ML259577