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Safety and Efficacy of Ranibizumab for Diabetic Macular Edema (REACT)

Primary Purpose

Diabetic Macular Edema

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

About this trial

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

Eligibility Criteria

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

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 > 18 years
    • ETDRS best-corrected visual acuity of 20/25 to 20/320 in the study eye
    • Willing, committed, and able to return for ALL clinic visits and complete all study related procedures
    • At least 6 previous bevacizumab injections for diabetic macular edema in the last 12 months in the study eye.
    • At least 2 bevacizumab injections within 10 weeks and the most recent bevacizumab injection within 6 weeks of baseline study visits in the study eye.
    • Persistent foveal-involving diabetic macular edema based on presence of intraretinal and/or subretinal fluid by SDOCT in the foveal center at study entry in the study eye.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from this study:

  • 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 IUD (intrauterine device), or contraceptive hormone implant or patch.
  • Intravitreal steroid or periocular steroid treatment within 3 months of study entry in the study eye.
  • Focal/grid laser photocoagulation treatment within 3 months of study entry in the study eye.
  • Panretinal photocoagulation treatment within 3 months of study entry in the study eye.
  • Prior vitrectomy in the study eye
  • History of retinal detachment in the study eye
  • Prior trabeculectomy or other filtration surgery in the study eye
  • Active intraocular inflammation in either eye
  • Active ocular or periocular infection in either eye
  • Active scleritis or episcleritis in either eye
  • History of any other retinal vascular disease (e.g., retinal vein occlusion, retinal artery occlusion) in the study eye.
  • Coexistent retinal disease other than diabetic retinopathy (e.g., AMD (age related macular degeneration), inherited retinal disease) in the study eye.
  • Intraocular surgery within 3 months of study entry in the study eye.
  • History of corneal transplant or corneal dystrophy in the study eye.
  • Significant media opacities in study eye which may interfere with visual acuity in the study eye.
  • Participation as a subject in any clinical study within 3 months of study entry.
  • History of allergy to topical iodine
  • 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

Sites / Locations

  • Cole Eye Institute, Cleveland Clinic
  • Cole Eye Institute at Hillcrest Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Group I - Monthly

Group II - Treat-and-Extend

Arm Description

Enrolled subjects will receive multiple open-label intravitreal injections of 0.3 mg ranibizumab administered every 28 days (+/- 7 days from the last treatment) for 12 months in the monthly group.

Enrolled subjects will initially receive 3 loading doses of open-label Ranibizumab 0.3 mg given via intravitreal injection every 28 days (+/- 7 days from the last treatment). After the third loading dose, the follow-up interval is determined by the Principal Investigator based on OCT results as stated in the protocol. The follow-up interval is increased by 2 weeks (+/- 7 days) at each visit up to a maximum interval of 12 weeks (+/- 7 days). There is criteria built into the protocol in case a reduction in the follow-up intervals becomes necessary based upon worsening OCT results.

Outcomes

Primary Outcome Measures

Number of Participants With Non-severe Ocular Adverse Events
As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.
Number of Participants With Severe Ocular Adverse Events
As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs.
Number of Participants With Non-severe Non-ocular Adverse Event
As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.
Number of Participants With Severe Non-ocular Adverse Event
As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.

Secondary Outcome Measures

Mean Change in BCVA
Mean change in best-corrected visual acuity as assessed by the number of letters read correctly on the electronic ETDRS eye chart from baseline to months 6 and 12.
Mean Change in Central Foveal Thickness
Mean absolute change from baseline central foveal thickness at months 6 and 12 as measured by SDOCT (defined as the average thickness within the central 1 mm subfield)
Anatomically Dry Eyes by SDOCT
Number of participants with an anatomically "dry" study eye by SDOCT at months 6 and 12
Gain in Vision Greater Than or Equal to 15 Letters
Number of participants that gained greater than or equal to 15 letters of vision in their study eye at months 6 and 12.
Loss in Vision Greater Than or Equal to 15 Letters
Number of participants that lost greater than or equal to 15 letters of vision in their study eye at months 6 and 12.
Participants With BCVA at 20/40 or Better
Number of participants with 20/40 or better best-corrected visual acuity in their study eye at months 6 and 12.
Number of Participants With Angiographic Leakage
Number of participants with angiographic leakage in their study eye measured from baseline to months 3, 6 and 12 (i.e. presence of leakage).
Number of Participants With Nonperfusion
Number of participants with peripheral nonperfusion in their study eye from baseline to months 3, 6, and 12 (i.e. presence of ischemia).

Full Information

First Posted
October 29, 2013
Last Updated
October 30, 2020
Sponsor
Justis Ehlers
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01982435
Brief Title
Safety and Efficacy of Ranibizumab for Diabetic Macular Edema
Acronym
REACT
Official Title
Safety and Efficacy of Intravitreal Ranibizumab for Diabetic Macular Edema Previously Treated With Intravitreal Bevacizumab: A Randomized Dual Arm Comparative Dosing Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
June 24, 2014 (Actual)
Primary Completion Date
May 26, 2016 (Actual)
Study Completion Date
May 26, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Justis Ehlers
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to assess the ocular and systemic adverse events of ranibizumab (Lucentis)for DME (diabetic macular edema) following previous treatment with intravitreal bevacizumab (Avastin).
Detailed Description
This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab (Lucentis) in subjects with DME (diabetic macular edema) previously treated with intravitreal bevacizumab (Avastin) with a randomized comparative dosing strategy, monthly vs "treat-and-extend." Thirty patients total will be enrolled in the study, 15 in each group. This study will have a 1-year treatment period. The recruitment period will occur over 1 year with total potential study duration of 2 years.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group I - Monthly
Arm Type
Other
Arm Description
Enrolled subjects will receive multiple open-label intravitreal injections of 0.3 mg ranibizumab administered every 28 days (+/- 7 days from the last treatment) for 12 months in the monthly group.
Arm Title
Group II - Treat-and-Extend
Arm Type
Other
Arm Description
Enrolled subjects will initially receive 3 loading doses of open-label Ranibizumab 0.3 mg given via intravitreal injection every 28 days (+/- 7 days from the last treatment). After the third loading dose, the follow-up interval is determined by the Principal Investigator based on OCT results as stated in the protocol. The follow-up interval is increased by 2 weeks (+/- 7 days) at each visit up to a maximum interval of 12 weeks (+/- 7 days). There is criteria built into the protocol in case a reduction in the follow-up intervals becomes necessary based upon worsening OCT results.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Monthly injections of Intravitreal Ranibizumab 0.3 mg for 12 months in patients previously treated with Avastin for Diabetic Macular Edema.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Three Monthly injections of Intravitreal Ranibizumab 0.3 mg in patients previously treated with Avastin for Diabetic Macular Edema. Then follow-up visits may be extended by 2 weeks for a total of 12 months.
Primary Outcome Measure Information:
Title
Number of Participants With Non-severe Ocular Adverse Events
Description
As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.
Time Frame
12 months
Title
Number of Participants With Severe Ocular Adverse Events
Description
As identified by eye examination (including visual acuity testing), identified by physical examination, subject reporting, and changes in vital signs.
Time Frame
12 months
Title
Number of Participants With Non-severe Non-ocular Adverse Event
Description
As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.
Time Frame
12 months
Title
Number of Participants With Severe Non-ocular Adverse Event
Description
As identified by physical examination, subject reporting, and changes in vital signs. These outcome measures are also included in more detail in the adverse event section of the results.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Mean Change in BCVA
Description
Mean change in best-corrected visual acuity as assessed by the number of letters read correctly on the electronic ETDRS eye chart from baseline to months 6 and 12.
Time Frame
Months 6 and 12
Title
Mean Change in Central Foveal Thickness
Description
Mean absolute change from baseline central foveal thickness at months 6 and 12 as measured by SDOCT (defined as the average thickness within the central 1 mm subfield)
Time Frame
Months 6 and 12
Title
Anatomically Dry Eyes by SDOCT
Description
Number of participants with an anatomically "dry" study eye by SDOCT at months 6 and 12
Time Frame
Months 6 and 12
Title
Gain in Vision Greater Than or Equal to 15 Letters
Description
Number of participants that gained greater than or equal to 15 letters of vision in their study eye at months 6 and 12.
Time Frame
Months 6 and 12
Title
Loss in Vision Greater Than or Equal to 15 Letters
Description
Number of participants that lost greater than or equal to 15 letters of vision in their study eye at months 6 and 12.
Time Frame
Months 6 and 12
Title
Participants With BCVA at 20/40 or Better
Description
Number of participants with 20/40 or better best-corrected visual acuity in their study eye at months 6 and 12.
Time Frame
Months 6 and 12
Title
Number of Participants With Angiographic Leakage
Description
Number of participants with angiographic leakage in their study eye measured from baseline to months 3, 6 and 12 (i.e. presence of leakage).
Time Frame
3, 6 and 12 months
Title
Number of Participants With Nonperfusion
Description
Number of participants with peripheral nonperfusion in their study eye from baseline to months 3, 6, and 12 (i.e. presence of ischemia).
Time Frame
3, 6 and 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 > 18 years ETDRS best-corrected visual acuity of 20/25 to 20/320 in the study eye Willing, committed, and able to return for ALL clinic visits and complete all study related procedures At least 6 previous bevacizumab injections for diabetic macular edema in the last 12 months in the study eye. At least 2 bevacizumab injections within 10 weeks and the most recent bevacizumab injection within 6 weeks of baseline study visits in the study eye. Persistent foveal-involving diabetic macular edema based on presence of intraretinal and/or subretinal fluid by SDOCT in the foveal center at study entry in the study eye. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: 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 IUD (intrauterine device), or contraceptive hormone implant or patch. Intravitreal steroid or periocular steroid treatment within 3 months of study entry in the study eye. Focal/grid laser photocoagulation treatment within 3 months of study entry in the study eye. Panretinal photocoagulation treatment within 3 months of study entry in the study eye. Prior vitrectomy in the study eye History of retinal detachment in the study eye Prior trabeculectomy or other filtration surgery in the study eye Active intraocular inflammation in either eye Active ocular or periocular infection in either eye Active scleritis or episcleritis in either eye History of any other retinal vascular disease (e.g., retinal vein occlusion, retinal artery occlusion) in the study eye. Coexistent retinal disease other than diabetic retinopathy (e.g., AMD (age related macular degeneration), inherited retinal disease) in the study eye. Intraocular surgery within 3 months of study entry in the study eye. History of corneal transplant or corneal dystrophy in the study eye. Significant media opacities in study eye which may interfere with visual acuity in the study eye. Participation as a subject in any clinical study within 3 months of study entry. History of allergy to topical iodine 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Justis Ehlers, M.D.
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cole Eye Institute, Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Cole Eye Institute at Hillcrest Hospital
City
Mayfield Heights
State/Province
Ohio
ZIP/Postal Code
44124
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Efficacy of Ranibizumab for Diabetic Macular Edema

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