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

Safety and Efficacy of Intravitreal Ranibizumab for Diabetic Macular Edema Previously Treated With Intravitreal Bevacizumab: A Randomized Dual Arm Comparative Dosing Trial

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).

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Ranibizumab; Drug: Ranibizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cole Eye Institute, Cleveland Clinic
    • Mayfield Heights, Ohio, United States, 44124
      • Cole Eye Institute at Hillcrest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Group I - Monthly; 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.	Drug: Ranibizumab; Monthly injections of Intravitreal Ranibizumab 0.3 mg for 12 months in patients previously treated with Avastin for Diabetic Macular Edema.; Other Names: Lucentis; Drug: Ranibizumab; 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.; Other Names: Lucentis
OTHER: Group II - Treat-and-Extend; 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.	Drug: Ranibizumab; Monthly injections of Intravitreal Ranibizumab 0.3 mg for 12 months in patients previously treated with Avastin for Diabetic Macular Edema.; Other Names: Lucentis; Drug: Ranibizumab; 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.; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months
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.	12 months
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.	12 months
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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)	Months 6 and 12
Anatomically Dry Eyes by SDOCT	Number of participants with an anatomically "dry" study eye by SDOCT at months 6 and 12	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.	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.	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.	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).	3, 6 and 12 months
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).	3, 6 and 12 months

Collaborators and Investigators

• Sponsor: Justis Ehlers
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Justis Ehlers, M.D., The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 24, 2014
• Primary Completion (ACTUAL): May 26, 2016
• Study Completion (ACTUAL): May 26, 2016

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: November 4, 2013
• First Posted (ESTIMATE): November 13, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Macular Edema
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: REACT Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO