12/22/2021
`
`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
`
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`
`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular
`Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RIDE) (RIDE)
`
`The safety and scientific validity of this study is the responsibility of the study sponsor
`and investigators. Listing a study does not mean it has been evaluated by the U.S.
`Federal Government. Read our disclaimer for details.
`
`
`ClinicalTrials.gov Identifier: NCT00473382
`
`Recruitment Status  : Completed
`First Posted  : May 15, 2007
`Results First Posted  : January 17, 2013
`Last Update Posted  : April 17, 2017
`
`Sponsor:
`Genentech, Inc.
`
`Information provided by (Responsible Party):
`
`https://clinicaltrials.gov/ct2/show/NCT00473382
`
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
`Genentech, Inc.
`
`Study Details
`
`Tabular View
`
`Study Results
`
`Disclaimer
`
`How to Read a Study Record
`
`Study Description
`
`Brief Summary:
`
`Go to
`
`This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled study of the
`efficacy and safety of ranibizumab injection in patients with clinically significant macular edema with center
`involvement (CSME-CI) secondary to diabetes mellitus (Type 1 or 2). This study is identical in design to study
`NCT00473330 (Protocol ID FVF4170g).
`
`The open-label extension phase of the study was stopped after receiving FDA approval of the study drug
`(ranibizumab) for diabetic macular edema.
`
`Condition or disease 
`
`Intervention/treatment 
`
`Diabetes Mellitus
`
`Macular Edema
`
`Drug: Ranibizumab
`
`Drug: Sham injection
`
`Phase 
`
`Phase 3
`
`Detailed Description:
`This study is composed of 3 phases: (1) A 24-month controlled treatment period (monthly treatment with
`ranibizumab 0.3 mg, ranibizumab 0.5 mg, or sham injection) followed by (2) a 12-month treatment period in
`which patients randomized to the sham group who had not discontinued from treatment (still masked) could
`choose to receive monthly ranibizumab 0.5 mg while the 2 ranibizumab treatment groups continued on the
`same treatment they received in the first 2 years. Patients who had not discontinued treatment by Month 36
`were eligible to continue treatment with ranibizumab 0.5 mg as needed (pro re nata, PRN) in (3) an extension
`phase of the study for up to 2 more years, resulting in up to 5 years possible total treatment time for some
`patients.
`
`As per the protocol, Genentech terminated the study approximately 30 days after approval of ranibizumab for
`diabetic macular edema in the United States.
`
`Study Design
`
`Study Type  :
`Interventional (Clinical Trial)
`Actual Enrollment  :
`382 participants
`
`Go to
`
`https://clinicaltrials.gov/ct2/show/NCT00473382
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
`
`Allocation:
`Randomized
`Intervention Model:
`Parallel Assignment
`Masking:
`Double (Participant, Investigator)
`Primary Purpose:
`Treatment
`Official Title:
`A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and
`Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center
`Involvement Secondary to Diabetes Mellitus
`Study Start Date  :
`June 2007
`Actual Primary Completion Date  :
`January 2011
`Actual Study Completion Date  :
`September 2012
`
`Resource links provided by the National Library of Medicine
`
`MedlinePlus related topics: Edema
`
`Drug Information available for: Ranibizumab
`
`U.S. FDA Resources
`
`Arms and Interventions
`
`Go to
`
`Arm 
`
`Intervention/treatment 
`
`https://clinicaltrials.gov/ct2/show/NCT00473382
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
`
`Intervention/treatment 
`
`Drug: Ranibizumab
`Sterile solution for intravitreal injection.
`Other Name: Lucentis
`
`Drug: Ranibizumab
`Sterile solution for intravitreal injection.
`Other Name: Lucentis
`
`Drug: Sham injection
`
`Arm 
`
`Experimental: Ranibizumab 0.3 mg
`Patients received ranibizumab 0.3 mg monthly
`administered intravitreally for 36 months. Patients
`who had not discontinued treatment by Month 36
`could enter the open-label extension phase to
`receive ranibizumab 0.5 mg as needed (pro re
`nata [PRN]) for up to 24 additional months.
`
`Experimental: Ranibizumab 0.5 mg
`Patients received ranibizumab 0.5 mg monthly
`administered intravitreally for 36 months. Patients
`who had not discontinued treatment by Month 36
`could enter the open-label extension phase to
`receive ranibizumab 0.5 mg as needed (pro re
`nata [PRN]) for up to 24 additional months.
`
`Sham Comparator: Sham injection/ranibizumab 0.5
`mg
`Patients received a sham intravitreal injection
`monthly for 24 months. Patients who had not
`discontinued treatment by Month 24 could choose
`to receive ranibizumab 0.5 mg monthly
`administered intravitreally for the subsequent 12
`months. Patients who had not discontinued
`treatment by Month 36 could enter the open-label
`extension phase to receive ranibizumab 0.5 mg
`as needed (pro re nata [PRN]) for up to 24
`additional months.
`
`Outcome Measures
`
`Go to
`
`Primary Outcome Measures  :
`1. Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score
`From Baseline at Month 24 [ Time Frame: Baseline to Month 24 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
`
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
`
`Secondary Outcome Measures  :
`1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24, 36, and
`48 [ Time Frame: Baseline to Month 48 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A
`positive change score indicates improvement.
`
`2. Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24,
`36, and 48 [ Time Frame: Months 24, 36, and 48 ]
`
`VA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`chart starting at a test distance of 4 meters. An increase in the number of lines read correctly by the
`patient in the ETDRS chart indicates an improvement of vision. The Snellen equivalent of 20/40 or
`better is 69 or more letters correctly read in the EDTRS chart.
`
`3. Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score
`From Baseline at Months 24, 36, and 48 [ Time Frame: Baseline to Month 48 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
`
`4. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in
`Patients With Focal Edema at Baseline [ Time Frame: Baseline to Month 36 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A
`positive change score indicates improvement.
`
`5. Mean Change From Baseline in Central Foveal Thickness at Months 24, 36, and 48
`[ Time Frame: Baseline to Month 48 ]
`
`Central foveal thickness was assessed in optical coherence tomographic images by the central
`reading center. A decrease in foveal thickness suggests a reduction in macular edema. A negative
`change score indicates improvement.
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
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`6. Percentage of Patients With a ≥ 3-step Worsening From Baseline in the Early Treatment Diabetic
`Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale Score for Eyes at Months 24 and
`36 [ Time Frame: Baseline to Month 36 ]
`
`The severity of diabetic retinopathy was graded on a 10-point scale by the central reading center by
`comparing patient fundus photographic images with a set of standard images. 1=diabetic retinopathy
`(DR) severity level 10, 12 (DR absent), 2=DR severity level 14A-14C, 14Z, 15, 20 (DR questionable,
`microaneurysms only), 3=DR severity level 35A-35F (mild non-proliferative [NP]DR), 4=DR severity
`level 43A, 43B (moderate NPDR), 5=DR severity level 47A-47D (moderately severe NPDR), 6=DR
`severity level 53A-53E (severe NPDR), 7=DR severity level 60, 61A, 61B (mild proliferative [P]DR),
`8=DR severity level 65A-65C (moderate PDR), 9=DR severity level 71A-71D (high-risk PDR),
`10=DR severity level 90 (cannot grade). A lower score indicates less severe diabetic retinopathy.
`
`7. Percentage of Patients With Resolution of Leakage at Month 24 [ Time Frame: Baseline to Month
`24 ]
`
`Resolution of leakage was defined as total area of fluorescein leakage in the central, inner, and
`outer subfields of the 0 Disc Area. Leakage was assessed in fluorescein angiographic images by the
`central reading center.
`
`8. Mean Number of Macular Laser Treatments From Baseline Through Months 24 and 36
`[ Time Frame: Baseline to Month 36 ]
`
`The need for macular laser treatment was evaluated by the masked (evaluating) physician. Macular
`laser was administered per protocol-specified objective and subjective criteria starting at Month 3.
`
`9. Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA)
`Score From Baseline at Months 36 and 48 [ Time Frame: Baseline to Month 48 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
`
`10. Mean Change From Month 36 in Best Corrected Visual Acuity (BCVA) Score in the Study Eye at
`Month 48 [ Time Frame: Month 36 to Month 48 ]
`
`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision. A
`positive change score indicates improvement.
`
`11. Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score in
`the Study Eye From Month 36 at Month 48 [ Time Frame: Month 36 to Month 48 ]
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
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`BCVA was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity
`(VA) chart starting at a test distance of 4 meters. The BCVA score is the number of letters read
`correctly by the patient. An increase in the BCVA score indicates an improvement of vision.
`
`12. Mean Change From Month 36 in Central Foveal Thickness in the Study Eye at Month 48
`[ Time Frame: Month 36 to Month 48 ]
`
`Central foveal thickness was assessed in optical coherence tomographic images by the central
`reading center. A decrease in foveal thickness suggests a reduction in macular edema. A negative
`change score indicates improvement.
`
`Eligibility Criteria
`
`Go to
`
`Information from the National Library of Medicine
`
`Choosing to participate in a study is an important personal decision. Talk with your doctor and family
`members or friends about deciding to join a study. To learn more about this study, you or your doctor may
`contact the study research staff using the contacts provided below. For general information, Learn About
`Clinical Studies.
`
`Ages Eligible for Study:
`18 Years and older (Adult, Older Adult)
`Sexes Eligible for Study:
`All
`Accepts Healthy Volunteers:
`No
`
`Criteria
`Inclusion Criteria:
`
`Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and
`Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
`Age ≥ 18 years.
`Diabetes mellitus (Type 1 or 2) .
`
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`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Di…
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`Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea with central
`macular thickness ≥ 275 µm in the center subfield as assessed on optical coherence tomography (OCT).
`Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320 approximate Snellen
`equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing
`distance of 4 meters.
`Decrease in vision determined to be primarily the result of DME and not to other causes.
`For sexually active women of childbearing potential, use of an appropriate form of contraception (or
`abstinence) for the duration of the study.
`Ability (in the opinion of the investigator) and willingness to return for all scheduled visits and assessments.
`
`Exclusion Criteria:
`
`History of vitreoretinal surgery in the study eye.
`Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of
`screening.
`Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone acetonide [TA]) within 3
`months of screening.
`Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate,
`bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first day of treatment) visit.
`Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR.
`Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the
`macula in the study eye.
`
`Concurrent Ocular Conditions
`
`Vitreomacular traction or epiretinal membrane in the study eye.
`Ocular inflammation (including trace or above) in the study eye.
`History of idiopathic or autoimmune uveitis in either eye.
`Structural damage to the center of the macula in the study eye that is likely to preclude improvement in VA
`following the resolution of macular edema, including atrophy of the retinal pigment epithelium (RPE),
`subretinal fibrosis, 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 (CNV) of any cause
`(eg, age-related macular degeneration (AMD), ocular histoplasmosis, or pathologic myopia).
`Concurrent disease in the study eye that would compromise visual acuity or require medical or surgical
`intervention during the study period.
`Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser capsulotomy
`within the past 2 months, or any other intraocular surgery within the 90 days preceding Day 0.
`Aphakia or absence of the posterior capsule in the study eye.
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`Uncontrolled glaucoma or previous filtration surgery in the study eye.
`Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
`Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current
`treatment for serious systemic infection.
`Uncontrolled blood pressure.
`History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
`Uncontrolled diabetes mellitus.
`Renal failure requiring dialysis or renal transplant.
`Participation in an investigational trial within 30 days prior to screening that involved treatment with any
`drug (excluding vitamins and minerals) or device.
`History of other disease, 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 renders the subject at high risk from treatment
`complications.
`Pregnancy or lactation.
`History of allergy to fluorescein.
`History of allergy to ranibizumab injection or related molecule.
`
`Contacts and Locations
`
`Go to
`
`Information from the National Library of Medicine
`
`To learn more about this study, you or your doctor may contact the study research staff using the contact
`information provided by the sponsor.
`
`Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00473382
`
`Sponsors and Collaborators
`Genentech, Inc.
`
`Investigators
`Study Director:
`
`Jason Ehrlich, M.D., Ph.D. Genentech, Inc.
`
`More Information
`
`Go to
`
`Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
`https://clinicaltrials.gov/ct2/show/NCT00473382
`
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`Gonzalez VH, Wang PW, Ruiz CQ. Panretinal Photocoagulation for Diabetic Retinopathy in the RIDE and
`RISE Trials: Not "1 and Done". Ophthalmology. 2021 Oct;128(10):1448-1457. doi:
`10.1016/j.ophtha.2019.08.010. Epub 2019 Aug 21.
`
`Wykoff CC, Eichenbaum DA, Roth DB, Hill L, Fung AE, Haskova Z. Ranibizumab Induces Regression of
`Diabetic Retinopathy in Most Patients at High Risk of Progression to Proliferative Diabetic Retinopathy.
`Ophthalmol Retina. 2018 Oct;2(10):997-1009. doi: 10.1016/j.oret.2018.06.005. Epub 2018 Aug 1.
`
`Sun JK, Wang PW, Taylor S, Haskova Z. Durability of Diabetic Retinopathy Improvement with As-Needed
`Ranibizumab: Open-Label Extension of RIDE and RISE Studies. Ophthalmology. 2019 May;126(5):712-720.
`doi: 10.1016/j.ophtha.2018.10.041. Epub 2018 Nov 9.
`
`Reddy RK, Pieramici DJ, Gune S, Ghanekar A, Lu N, Quezada-Ruiz C, Baumal CR. Efficacy of Ranibizumab
`in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE. Ophthalmology. 2018
`Oct;125(10):1568-1574. doi: 10.1016/j.ophtha.2018.04.002. Epub 2018 May 8.
`
`Moshfeghi AA, Shapiro H, Lemmon LA, Gune S. Impact of Cataract Surgery during Treatment with
`Ranibizumab in Patients with Diabetic Macular Edema. Ophthalmol Retina. 2018 Feb;2(2):86-90. doi:
`10.1016/j.oret.2017.05.003. Epub 2017 Jul 27.
`
`Singh RP, Habbu K, Ehlers JP, Lansang MC, Hill L, Stoilov I. The Impact of Systemic Factors on Clinical
`Response to Ranibizumab for Diabetic Macular Edema. Ophthalmology. 2016 Jul;123(7):1581-7. doi:
`10.1016/j.ophtha.2016.03.038. Epub 2016 May 24.
`
`Pieramici DJ, Wang PW, Ding B, Gune S. Visual and Anatomic Outcomes in Patients with Diabetic Macular
`Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE. Ophthalmology. 2016
`Jun;123(6):1345-50. doi: 10.1016/j.ophtha.2016.02.007. Epub 2016 Mar 15.
`
`Bressler NM, Varma R, Mitchell P, Suñer IJ, Dolan C, Ward J, Ferreira A, Ehrlich JS, Turpcu A. Effect of
`Ranibizumab on the Decision to Drive and Vision Function Relevant to Driving in Patients With Diabetic
`Macular Edema: Report From RESTORE, RIDE, and RISE Trials. JAMA Ophthalmol. 2016 Feb;134(2):160-6.
`doi: 10.1001/jamaophthalmol.2015.4636.
`
`Boyer DS, Nguyen QD, Brown DM, Basu K, Ehrlich JS; RIDE and RISE Research Group. Outcomes with As-
`Needed Ranibizumab after Initial Monthly Therapy: Long-Term Outcomes of the Phase III RIDE and RISE
`Trials. Ophthalmology. 2015 Dec;122(12):2504-13.e1. doi: 10.1016/j.ophtha.2015.08.006. Epub 2015 Oct 9.
`
`Bansal AS, Khurana RN, Wieland MR, Wang PW, Van Everen SA, Tuomi L. Influence of Glycosylated
`Hemoglobin on the Efficacy of Ranibizumab for Diabetic Macular Edema: A Post Hoc Analysis of the
`RIDE/RISE Trials. Ophthalmology. 2015 Aug;122(8):1573-9. doi: 10.1016/j.ophtha.2015.04.029. Epub 2015
`Jun 4.
`
`Bressler NM, Varma R, Suñer IJ, Dolan CM, Ward J, Ehrlich JS, Colman S, Turpcu A; RIDE and RISE
`Research Groups. Vision-related function after ranibizumab treatment for diabetic macular edema: results from
`
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`RIDE and RISE. Ophthalmology. 2014 Dec;121(12):2461-72. doi: 10.1016/j.ophtha.2014.07.008. Epub 2014
`Aug 20.
`
`Campochiaro PA, Wykoff CC, Shapiro H, Rubio RG, Ehrlich JS. Neutralization of vascular endothelial growth
`factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology. 2014
`Sep;121(9):1783-9. doi: 10.1016/j.ophtha.2014.03.021. Epub 2014 Apr 24.
`
`Brown DM, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, Schlottmann PG, Rundle AC, Zhang J,
`Rubio RG, Adamis AP, Ehrlich JS, Hopkins JJ; RIDE and RISE Research Group. Long-term outcomes of
`ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and
`RIDE. Ophthalmology. 2013 Oct;120(10):2013-22. doi: 10.1016/j.ophtha.2013.02.034. Epub 2013 May 22.
`
`Ip MS, Domalpally A, Hopkins JJ, Wong P, Ehrlich JS. Long-term effects of ranibizumab on diabetic
`retinopathy severity and progression. Arch Ophthalmol. 2012 Sep;130(9):1145-52. doi:
`10.1001/archophthalmol.2012.1043.
`
`Responsible Party:
`Genentech, Inc.
`ClinicalTrials.gov Identifier:
`NCT00473382 History of Changes
`Other Study ID Numbers:
`FVF4168g
`First Posted:
`May 15, 2007 Key Record Dates
`Results First Posted:
`January 17, 2013
`Last Update Posted:
`April 17, 2017
`Last Verified:
`March 2017
`
`Keywords provided by Genentech, Inc.:
`Lucentis
`DME
`Diabetes
`Vision loss
`
`Additional relevant MeSH terms:
`
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`Macular Edema
`Diabetes Mellitus
`Edema
`Glucose Metabolism Disorders
`Metabolic Diseases
`Endocrine System Diseases
`Macular Degeneration
`Retinal Degeneration
`Retinal Diseases
`Eye Diseases
`Ranibizumab
`Angiogenesis Inhibitors
`Angiogenesis Modulating Agents
`Growth Substances
`Physiological Effects of Drugs
`Growth Inhibitors
`Antineoplastic Agents
`
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