|Principal Investigator: Rachael Jacoby|
|Keywords: Diabetic eye disease , Treatment trial||Department: Ophthalmology-Services|
|IRB Number: 00115547|
|Specialty: Ophthalmology, Ophthalmology|
|Sub Specialties: Diabetic Retinopathy, Retinal Diseases|
|Recruitment Status: Active, not recruiting|
To determine the safety and effectiveness of the study compound in treating patients with macular edema secondary to diabetic retinopathy
General Inclusion Criteria
Willingness and the ability to provide signed informed consent. Additionally, at U.S. sites, patients must provide Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
Age >18 years
Documented diagnosis of diabetes mellitus (Type 1 or Type 2), as defined by the American Diabetes Association or per WHO criteria and
Current regular use of insulin for the treatment of diabetes
Current regular use of oral anti-hyperglycemic agents for the treatment of diabetes
HbA1c of <10% within 2 months prior to the Day 1 visit date
Ability and willingness to undertake all scheduled visits and assessments
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements. Examples of acceptable contraceptive methods include bilateral tubal ligation, male sterilization; hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices; copper intrauterine devices.
Contraception methods that do not result in a failure rate of <1% per year such as male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide are not acceptable.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. If a patient is usually not sexually active but becomes active, they, with their partner, must comply with the contraceptive requirements of the study.
For patients enrolled in the China extension at China FDA-recognized sites: current residents of mainland China, Hong Kong, or Taiwan
Ocular Inclusion Criteria for Study Eye
Macular thickening secondary to DME involving the center of the fovea with CST > 325 µm, as measured on Spectralis SD-OCT, or >315 µm, as measured on Cirrus SD-OCT or Topcon SD-OCT at screening
BCVA of 73 to 25 letters, inclusive (20/40 to 20/320 approximate Snellen equivalent), using the ETDRS protocol at the initial testing distance of 4 meters (see the BCVA manual for additional details) on Day 1
Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality CFPs (including ETDRS 7 modified fields or 4 wide-angle fields to permit grading of DR and assessment of the retina) and other imaging modalities.
General Exclusion Criteria
Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication or insulin within 3 months prior to Day 1
History of allergy or hypersensitivity to active drug aflibercept and any of its excipients, fluorescein, or any study treatment-related mandatory ingredients (e.g., disinfectants, anesthetics, etc.; see the pharmacy manual for additional details) that is not amenable to treatment
History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the RO6867461 or to aflibercept injections, study treatment procedure, dilating drops, or any of the anesthetic and antimicrobial drops used by a patient during the study
Active cancer within the past 12 months except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of < 6 and a stable prostate-specific antigen for > 12 months
Systemic treatment for suspected or active systemic infection - Ongoing use of prophylactic antibiotic therapy may be acceptable but has to be discussed with the Medical Monitor.
Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis within 6 months prior to Day 1 or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
History of other disease, other non-diabetic metabolic dysfunction, physical examination finding, historical or current clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of the RO6867461 or aflibercept or that might affect interpretation of the results of the study or renders the patient at high risk for treatment complications in the opinion of the investigator
Uncontrolled blood pressure (defined as systolic >180 mmHg and/or diastolic >100 mmHg while a patient is at rest) - If a patient’s initial reading exceeds these values, a second reading may be obtained later the same day or on another day during the screening period. If the patient’s blood pressure is controlled by antihypertensive medication, the patient should be taking the same medication continuously for at least 30 days prior to Day 1.
Stroke (Cerebral vascular accident) or myocardial infarction within 6 months prior to Day 1
Pregnancy or breastfeeding, or intention to become pregnant during the study - Women of childbearing potential must have a negative urine pregnancy test result within 28 days prior to initiation of study treatment. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test.
Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals) within 3 months prior to Day 1
Administration of systemic pro-angiogenic treatments, such as VEGF-based therapies for the peripheral or coronary ischemia (e.g., limb ischemia or myocardial infarction) within 3 months or 5 half-lives prior to Day 1
Inability to comply with study or follow-up procedures
Requirement for continuous use of any medications and treatments indicated in Section 4.4.2, Prohibited Therapy
Ocular Exclusion Criteria for Study Eye
High-risk PDR in the study eye, using any of the following established criteria for high-risk PDR:
Any vitreous or pre-retinal hemorrhage
Neovascularization elsewhere >1/2 disc area within an area equivalent to the mydriatic ETDRS 7 fields on clinical examination or on CFPs
Neovascularization at disc >1/3 disc area on clinical examination
Tractional retinal detachment, pre-retinal fibrosis, vitreomacular traction, or epiretinal membrane involving the fovea or disrupting the macular architecture in the study eye, as evaluated by the central reading center (CRC).
History of retinal detachment or macular hole (Stage 3 or 4)
Aphakia or implantation of anterior chamber intraocular lens
IVT anti-VEGF treatment within 3 months prior to Day 1 (applicable to patients whose study eyes were previously treated with IVT anti-VEGF agents) or any IVT anti-VEGF agents to study eye prior to Day 1 (applicable for patients who are treatment naive)
Treatment with panretinal photocoagulation (PRP) within 3 months prior to Day 1
Macular (focal or grid) laser within 3 months prior to Day 1
Any cataract surgery or treatment for complications of cataract surgery with steroids or YAG (yttrium-aluminum-garnet) laser capsulotomy within 3 months prior to Day 1
Any other intraocular surgery (e.g., corneal transplantation, glaucoma filtration, pars plana vitrectomy, corneal transplant, or radiotherapy)
Any IVT or periocular (subtenon) corticosteroid treatment within 6 months prior to Day 1
Any use of medicated intraocular implants, including Ozurdex®, within 6 months of Day 1
Any use of Iluvien® implants at any time prior to Day 1
Treatment for other retinal diseases that can lead to macular edema
Ocular Exclusion Criteria for Fellow Eye (Non-Study Eye)
Non-functioning nonstudy eye, defined as either:
BCVA of hand motion or worse
No physical presence of non-study eye (i.e., monocular)
Exclusion Criteria for Both Eyes
Prior administration of IVT RO6867461 in either eye
Any history of idiopathic or immune-mediated uveitis in either eye
Active ocular inflammation or suspected or active ocular or periocular infection in either eye on Day 1
Concurrent Ocular Conditions Exclusion Criteria
Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye (e.g., choroidal neovascularization, age-related macular degeneration, retinal vein occlusion, uveitis, angioid streaks, histoplasmosis, active or inactive cytomegalovirus, pathological myopia, retinal detachment, retinal embolus, macular traction, macular hole, and other)
Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye (e.g., foveal atrophy, foveal fibrosis, pigment abnormalities, dense subfoveal hard exudates, or other non-retinal conditions)
$2,775 for completion of 28 clinic visits over two years