Diabetic Macular Edema
Conditions
Brief summary
This study is designed to compare the post injection inflammation and pain seen after intravitreal injections of ranibizumab 0.3mg and aflibercept 2.0mg in patients with DME. The investigators will be evaluating patients (1-7 days) post injections for: 1\. Intraocular inflammation (defined as anterior chamber and/or vitreous cells 2. Pain (as measured on a standardized pain scale).
Detailed description
This is an open-label, Phase II study of post injection pain and inflammation after intravitreally administered ranibizumab and aflibercept in 100 subjects with Diabetic Macular Edema. Treatment naïve and experienced patients will be enrolled. Treatment experienced patients with history of anti-vegf injections will be eligible as long as they have not received any intravitreal injection in the 3 months prior to the study visit. Patients will be randomized to receive either Lucentis 0.3 mg or Eylea 2.0 mg, and followed for a week. A non-injecting masked physician who is blinded to the treatment drug will evaluate the patient at baseline before the injection and then within 1-2 days and 5-7 days after the injection for anterior chamber and vitreous cells using slit lamp examination and indirect ophthalmoscopy. Pain will also be recorded at these visits using a standardized pain scale. Consented, enrolled subjects will receive open-label intravitreal injection of either 0.3 mg ranibizumab or 2.0 mg aflibercept. A standard intravitreal injection protocol will be followed. Patients will be revaluated at baseline, 1-2 days and 5-7 days post injections. A non-injecting physician will evaluate the patients for anterior chamber and vitreous inflammation; this physician will be blinded about the specific treatment. Anterior chamber inflammation is described as any cell or flare in the anterior chamber. These will be evaluated using Standardization of Uveitis Nomenculature (SUN) working group classifications. Pain score will be evaluated using a Numerical Rating Scale.
Interventions
Ranibizumab 0.3 mg Patient will receive intravitreal injection of Ranibizumab 0.3 mg
Patient will receive intravitreal injection of Aflibercept 2.0 mg
Sponsors
Genentech, Inc.
Arshad Khanani
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects will be eligible if the following criteria are met: * Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 21 years * Exam and OCT confirming Diabetic Macular Edema * Visual Acuity of 20/400 or better * No history of post injection pain or inflammation in the past
Exclusion criteria
* Subjects who meet any of the following criteria will be excluded from this study * History of Endophthalmitis in either eye * Current inflammation in either eye * Uncontrolled or symptomatic Dry Eye Syndrome * Intravitreal injection less than 3 months ago * History of Anterior or Posterior Uveitis * History of post injection pain with prior treatments * Recent thromboembolic event (\<3 months) * Pregnancy (positive pregnancy test) or lactation * Premenopausal women not using adequate contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Intraocular Inflammation | 24 to 48 hours (visit #1) | Number of participants with intraocular inflammation as seen on slide lamp and dilated fundus exam. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale. | 24 to 48 hours visit #1 and 5 to 7 days visit #2 | Pain score rated on a 11 point numerical rating from 0-10 administered to each patient verbally at visit #1 and visit #2. 0 = no pain 10 = severe pain |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranibizumab 0.3 Intravitreal Injection Intravitreal injection of Ranibizumab 0.3 mg once
Ranibizumab 0.3 mg: Ranibizumab 0.3 mg Patient will receive intravitreal injection of Ranibizumab 0.3 mg | 51 |
| Aflibercept 2.0 mg Intravitreal Injection Intravitreal Aflibercept 2.0 mg once
Aflibercept 2.0 mg: Patient will receive intravitreal injection of Aflibercept 2.0 mg | 50 |
| Total | 101 |
Baseline characteristics
| Characteristic | Ranibizumab 0.3 Intravitreal Injection | Aflibercept 2.0 mg Intravitreal Injection | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 22 Participants | 24 Participants | 46 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 26 Participants | 55 Participants |
| Diabetic Macular Edema | 51 Participants | 50 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 12 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 38 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 40 Participants | 44 Participants | 84 Participants |
| Region of Enrollment United States | 51 participants | 50 participants | 101 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 39 Participants |
| Sex: Female, Male Male | 33 Participants | 29 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 6 / 51 | 10 / 50 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 |
Outcome results
Primary
Number of Participants With Intraocular Inflammation
Number of participants with intraocular inflammation as seen on slide lamp and dilated fundus exam.
Time frame: 24 to 48 hours (visit #1)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ranibizumab 0.3 Intravitreal Injection | Number of Participants With Intraocular Inflammation | 6 Participants |
| Aflibercept 2.0 mg Intravitreal Injection | Number of Participants With Intraocular Inflammation | 10 Participants |
Primary
Number of Participants With Intraocular Inflammation
Number of Participants With Intraocular Inflammation as seen on slit lamp and dilated fundus exam
Time frame: 5 to 7 days (visit #2)
Population: Inflammation 5 to 7 days after injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ranibizumab 0.3 Intravitreal Injection | Number of Participants With Intraocular Inflammation | 1 Participants |
| Aflibercept 2.0 mg Intravitreal Injection | Number of Participants With Intraocular Inflammation | 3 Participants |
Secondary
Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale.
Pain score rated on a 11 point numerical rating from 0-10 administered to each patient verbally at visit #1 and visit #2. 0 = no pain 10 = severe pain
Time frame: 24 to 48 hours visit #1 and 5 to 7 days visit #2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ranibizumab 0.3 Intravitreal Injection | Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale. | 24 to 48 hours visit #1 | 28 Participants |
| Ranibizumab 0.3 Intravitreal Injection | Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale. | 5 to 7 days visit #2 | 10 Participants |
| Aflibercept 2.0 mg Intravitreal Injection | Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale. | 24 to 48 hours visit #1 | 28 Participants |
| Aflibercept 2.0 mg Intravitreal Injection | Number of Participants With Post Injection Pain Above 0 on a 11 Point Pain Scale. | 5 to 7 days visit #2 | 5 Participants |