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Ranibizumab 0.5mg and 2.0mg to Treat Diabetic Macular Edema in Patients With Poor Response to Bevacizumab (REEF)

Primary Purpose

Diabetic Macular Edema

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ranibizumab
Sponsored by
California Retina Consultants
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring Diabetes, Macula, Edema, Retina

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to provide written informed consent and comply with study assessments for the full duration of the study
  • Age > 18 years
  • Diagnosis of diabetes mellitus (type 1 or 2)Any one of the following will be considered to be sufficient evidence that diabetes is present:Current regular use of insulin for treatment of diabetes or current regular use of oral anti-hyperglycemia agent for the treatment of diabetes
  • Clinical evidence of retinal thickening due to macular edema involving the center of the macula, associated with diabetic retinopathy.
  • Previous history of two consecutive intravitreal bevacizumab injections for the treatment of diabetic macular edema with documented incomplete resolution of central subfield thickening by OCT (consecutive injections administered < 7 weeks apart and within the past 12 months).
  • Central diabetic macular edema present on clinical examination and OCT testing with central 1mm subfield thickness greater than 300 microns as measured on SD-OCT.
  • Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 73 letters (20/40) by the ETDRS visual acuity protocol.
  • Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography

Exclusion Criteria:

  • Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception.
  • Participation in another ocular investigation or trial simultaneously
  • Blood pressure > 180/110 (systolic above 180 OR diastolic above 110)
  • Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse)
  • Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema
  • An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy)
  • Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gas)
  • Evidence of neovascularization of the iris or retina
  • Evidence of central atrophy or fibrosis in the study eye
  • Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study.
  • History of vitreous surgery in the study eye
  • History of cataract surgery within 6 months of enrollment.
  • History of YAG capsulotomy within 2 months of enrollment.
  • Visual acuity <20/400 in the fellow eye
  • Uncontrolled glaucoma (pressure >30) despite treatment with glaucoma medications.
  • History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.

Sites / Locations

  • California Retina Consultants
  • California Retina Consultants
  • California Retina Consultants
  • California Retina Consultants
  • Retina Institute of Hawai'i

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

0.5mg and 2.0mgRanibizumab

Arm Description

Three consecutive intravitreal ranibizumab 0.5mg injections followed by three consecutive intravitreal ranibizumab 2.0mg injections if specific criteria is met.

Outcomes

Primary Outcome Measures

Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline
To determine the mean change in the best-corrected visual acuity on an ETDRS visual acuity chart at a starting distance of 4 meters from baseline to 6 months.

Secondary Outcome Measures

Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline
To determine the mean change in central 1-mm subfield thickness as measured by spectral-domain OCT from baseline to 6 months .
Qualitative Assessment of Diabetic Macular Edema (DME)
To compare the percentage of subjects with compete or partial/no resolution of diabetic macular edema in response to the ranibizumab 0.5 and 2.0 mg doses.

Full Information

First Posted
February 7, 2011
Last Updated
March 23, 2016
Sponsor
California Retina Consultants
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01292798
Brief Title
Ranibizumab 0.5mg and 2.0mg to Treat Diabetic Macular Edema in Patients With Poor Response to Bevacizumab
Acronym
REEF
Official Title
Open Label, Phase I/II, Residual Edema Evaluation With 0.5mg and 2.0mg Ranibizumab Formulations (REEF)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
California Retina Consultants
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open-label, Phase I/II study of intravitreally administered ranibizumab either 0.5-mg and/or 2.0-mg in subjects with clinical, angiographic, and ocular coherence tomography (OCT) evidence of diabetic retinopathy with associated diabetic macular edema following bevacizumab therapy. Thirty patients will be enrolled in this study. Consented, enrolled subjects will receive multiple open-label intravitreal injections of 0.5 mg ranibizumab administered every 30 days (±7 days) for 3 injections during the mandatory treatment phase (Day 0, Month 1, and Month 2). Subjects with complete resolution of diabetic macular edema after 3 intravitreal injections of 0.5 mg ranibizumab will be treated as necessary with 0.5 mg ranibizumab to treat recurrent macular edema for an additional 9 months (12 months from Day 0). The intent is to administer additional ranibizumab treatment if there is evidence of disease activity documented on OCT (e.g., intra-retinal fluid, subretinal fluid and/or cystic changes). Subjects with residual diabetic macular edema following 3 intravitreal injections of 0.5 mg ranibizumab will be receive 3 intravitreal injections of 2.0 mg ranibizumab administered every 30 days (±7 days) for 3 injections at the Month 3, Month 4, and Month 5 study visits. Beginning at the Month 6 study visit, subjects with complete resolution of diabetic macular edema following 3 intravitreal injections of 2.0 mg ranibizumab will treated as necessary with 2.0 mg ranibizumab injections only to treat recurrent macular edema for an additional 6 months (12 months from Day 0). Subjects with residual diabetic macular edema following 3 consecutive intravitreal injections of 2.0 mg ranibizumab will be treated as necessary with 2.0 mg ranibizumab to treat persistent or recurrent macular edema for an additional 6 months (12 months from Day 0). Focal photocoagulation or intravitreal triamcinolone may be administered at the physician's discretion as an adjunct to ranibizumab injections beginning at Month 6 through Month 12 of the study. All subjects will make monthly visits for 12 months for evaluation of safety and efficacy. All subjects will have their first injection of ranibizumab on Day 0 and undergo a safety visit one week (±2 days) after the first injection. At subsequent visits, the subject will have a safety evaluation at the monthly scheduled follow-up visit prior to any intravitreal injection. Subjects will be contacted by the site personnel 1-2 days after each injection to elicit reports of decreased vision or pain or unusual new ocular symptoms in the study eye.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Macular Edema
Keywords
Diabetes, Macula, Edema, Retina

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
0.5mg and 2.0mgRanibizumab
Arm Type
Experimental
Arm Description
Three consecutive intravitreal ranibizumab 0.5mg injections followed by three consecutive intravitreal ranibizumab 2.0mg injections if specific criteria is met.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
0.05ml of 0.5mg or 2.0mg ranibizumab injected intravitreally
Primary Outcome Measure Information:
Title
Overall Mean Change in Visual Acuity Scores at Month 6 Compared to Baseline
Description
To determine the mean change in the best-corrected visual acuity on an ETDRS visual acuity chart at a starting distance of 4 meters from baseline to 6 months.
Time Frame
baseline and 6 months
Secondary Outcome Measure Information:
Title
Mean Change in 1-mm Central Subfield (CST) Thickness as Measured by OCT at Month 6 Compared to Baseline
Description
To determine the mean change in central 1-mm subfield thickness as measured by spectral-domain OCT from baseline to 6 months .
Time Frame
baseline and 6 months
Title
Qualitative Assessment of Diabetic Macular Edema (DME)
Description
To compare the percentage of subjects with compete or partial/no resolution of diabetic macular edema in response to the ranibizumab 0.5 and 2.0 mg doses.
Time Frame
Baeline and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study Age > 18 years Diagnosis of diabetes mellitus (type 1 or 2)Any one of the following will be considered to be sufficient evidence that diabetes is present:Current regular use of insulin for treatment of diabetes or current regular use of oral anti-hyperglycemia agent for the treatment of diabetes Clinical evidence of retinal thickening due to macular edema involving the center of the macula, associated with diabetic retinopathy. Previous history of two consecutive intravitreal bevacizumab injections for the treatment of diabetic macular edema with documented incomplete resolution of central subfield thickening by OCT (consecutive injections administered < 7 weeks apart and within the past 12 months). Central diabetic macular edema present on clinical examination and OCT testing with central 1mm subfield thickness greater than 300 microns as measured on SD-OCT. Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 73 letters (20/40) by the ETDRS visual acuity protocol. Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT testing and retinal photography Exclusion Criteria: Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception. Participation in another ocular investigation or trial simultaneously Blood pressure > 180/110 (systolic above 180 OR diastolic above 110) Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse) Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy) Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gas) Evidence of neovascularization of the iris or retina Evidence of central atrophy or fibrosis in the study eye Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study. History of vitreous surgery in the study eye History of cataract surgery within 6 months of enrollment. History of YAG capsulotomy within 2 months of enrollment. Visual acuity <20/400 in the fellow eye Uncontrolled glaucoma (pressure >30) despite treatment with glaucoma medications. History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dante Pieramici, MD
Organizational Affiliation
California Retina Consultants
Official's Role
Principal Investigator
Facility Information:
Facility Name
California Retina Consultants
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
California Retina Consultants
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
California Retina Consultants
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93103
Country
United States
Facility Name
California Retina Consultants
City
Santa Maria
State/Province
California
ZIP/Postal Code
93454
Country
United States
Facility Name
Retina Institute of Hawai'i
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
69815
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25633882
Citation
Dhoot DS, Pieramici DJ, Nasir M, Castellarin AA, Couvillion S, See RF, Steinle N, Bennett M, Rabena M, Avery RL. Residual edema evaluation with ranibizumab 0.5 mg and 2.0 mg formulations for diabetic macular edema (REEF study). Eye (Lond). 2015 Apr;29(4):534-41. doi: 10.1038/eye.2014.338. Epub 2015 Jan 30.
Results Reference
derived

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Ranibizumab 0.5mg and 2.0mg to Treat Diabetic Macular Edema in Patients With Poor Response to Bevacizumab

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