Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study

Diabetic Macular Edema Clinical Trial

— READ 3  

Official title:

Ranibizumab for Edema of the Macula in Diabetes: Protocol 3 With High Dose - the READ 3 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01077401
• Other study ID #: NA_00034586
• Status: Recruiting
• Phase: Phase 2
• First received: February 26, 2010
• Last updated: March 29, 2010
• Start date: February 2010
• Est. completion date: March 2013

Study information

• Verified date: February 2010
• Source: Johns Hopkins University
• Contact: Jennifer Denton
• Phone: 410-502-7621
• Email: jdenton2[@]jhmi.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety, tolerability, bioactivity, and dose response of two different dosages (0.5 mg and 2.0 mg) of ranibizumab (RBZ) in patients with diabetic macular edema (DME).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: March 2013
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Signed informed consent and authorization of use and disclosure of protected health information

• Age =18 years

• Diagnosis of diabetes mellitus (type 1 or type 2)

• Serum HbA1c = 5.5% within 12 months of randomization. Retinal thickening secondary to diabetes mellitus (diabetic macular edema) involving the center of the fovea

• Diagnosis must be confirmed by fluorescein angiography and OCT images

• Foveal thickness of = 250 µm,

• Best corrected visual acuity score in the study eye of 20/40 to 20/320 inclusive (Snellen equivalents using the ETDRS protocol at a distance of 4 meters). The non-study eye must be = 20 letters (approximate Snellen equivalent 20/400).

• In the opinion of the investigator, decreased vision in the study eye is due to foveal thickening from DME and not from other obvious causes of decreased vision If a female of childbearing potential, a negative pregnancy test and commitment to the use of at least two forms of effective contraception (birth control) for the duration of the study are necessary.

Exclusion Criteria:

• Panretinal photocoagulation or macular photocoagulation within 3 months of study entry in the study eye

• Use of intraocular or periocular injection of steroids in the study eye (e.g., triamcinolone) within 3 months of study entry

• Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium, ranibizumab, bevacizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry

• Proliferative diabetic retinopathy in the study eye, with the exceptions of

• Inactive, fibrotic proliferative diabetic retinopathy that has regressed following panretinal laser photocoagulation OR

• Tufts of NVE less than one disc area with no vitreous hemorrhage

• Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT

• Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), macular ischemia, or organized hard exudate plaque

• Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia)

• Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the first 6-month study period

• Cataract surgery in the study eye within 3 months of study entry; Yttrium-Aluminum- Garnet (YAG) laser capsulotomy within 1 month of study entry; or any other intraocular surgery within 3 months preceding Day 0.

• History of vitreoretinal surgery in the study eye within 3 months of study entry

• Uncontrolled glaucoma (defined as intraocular pressure =30 mm Hg despite treatment with anti-glaucoma medications)

• Blood pressure exceeding 180/100 (sitting) during the screening period

• Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin (HbA1c) value >13%

• Renal failure requiring dialysis or renal transplant

• Premenopausal women unwilling to commit to adequate contraception

• History of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or render the subject at high risk from treatment complications

• INR = 3.0 (e.g. due to current treatment with warfarin). The use of aspirin or other anticoagulants is not an exclusion

• History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 3 months of study enrollment.

• Have a history of hypersensitivity to ranibizumab or any of its components

• Have the presence of active malignancy, including lymphoproliferative disorders. Subjects with a history of fully resolved basal or squamous cell skin cancer may be enrolled.

Other

• Inability to comply with study or follow-up procedures

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetic Macular Edema
• Edema
• Macular Edema

Intervention

Drug:
• Ranibizumab
Intravitreal injections of ranibizumab 0.5mg dose for six monthly treatments then additional treatments with ranibizumab 0.5mg dose if the subject meets re-treatment criteria.
• ranibizumab
Intravitreal injections of ranibizumab 2.0 mg dose for six monthly treatments then additional treatments with ranibizumab 2.0 mg dose if the subject meets re-treatment criteria.

Locations

Country	Name	City	State
United States	Texas Retina Associates	Arlington	Texas
United States	Johns Hopkins University Wilmer Eye Institute	Baltimore	Maryland
United States	Retina Vitreous Associates	Beverly Hills	California
United States	Retina Group of Florida	Fort Lauderdale	Florida
United States	Retina Institute of Hawaii	Honolulu	Hawaii
United States	Illinois Retina Associates	Joliet	Illinois
United States	Eye Care Specialists	Kingston	Pennsylvania
United States	University of California San Diego	LaJolla	California
United States	Doheny Eye Institute	Los Angeles	California
United States	East Bay Retina Institute	Oakland	California
United States	University of Kansas	Prairie Village	Kansas
United States	Black Hills Eye Institute	Rapid City	South Dakota
United States	Retina Macula Institute	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Juvenile Diabetes Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	The primary outcome measures for safety and tolerability are the following: The incidence and severity of systemic and ocular adverse events that are associated with repeated intravitreal injections of two doses of RBZ in subjects with DME such as cardiovascular events, intraocular reactions (inflammation), vitreous hemorrhage, retinal detachment, endophthalmitis (intraocular infection),increased intraocular pressure, and cataract formation, among others.	3,6, 9 and 12 months	Yes
Secondary	Visual acuity	Mean change in BCVA (ETDRS) at 4 meters in the study eye over time through month 12.	3, 6, 9 and 12 months	No
Secondary	Anatomic Retinal changes	Anatomic retinal changes in the study eye as assessed by color fundus photography,fluorescein angiography, and OCT, from Baseline to Month 6 and Month 12, including: Extent of fluorescein leakage from CSME; Progression to proliferative diabetic retinopathy by ETDRS grade; Change in central retinal thickness, as assessed by OCT; Change in central retinal volume, as assessed by OCT.	3, 6, 9 and 12 months	Yes