2/12/24, 9:06 AM
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`A Study of RanibizumabInjection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Dia...
`
`The Wayback Machine- https://web.archive.org/web/20100609131649/http://clinicaltrials.gov:80/ct2/show/NCT00473330
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`A Study of RanibizumabInjection in Subjects With Clinically Significant Macular
`Edema With Center Involvement Secondary to Diabetes Mellitus (RISE)
`
`This study is ongoing, but not recruiting participants.
`
`First Received: May 13, 2007 Last Updated: November2, 2009 History of Changes
`
`
`
`» Purpose
`
`This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled study of the efficacy and safety of
`ranibizumabinjection in patients with CSME-CI secondary to diabetes mellitus (Type 1 or 2).
`
` Diabetes Mellitus
`
`Drug: ranibizumab
`Drug: sham
`
`Phase III
`
`Macular Edema
`
`Interventional
`Study Type:
`Study Design: Allocation: Randomized
`Control: Placebo Control
`Intervention Model: Parallel Assignment
`Masking: Double Blind (Subject, Investigator)
`Primary Purpose: Treatment
`
`Official Title:
`
`A Phase III, Double-Masked, Multicenter, Randomized, Sham Injection-Controlled Study of the Efficacy and
`Safety of RanibizumabInjection in Subjects With Clinically Significant Macular Edema With Center Involvement
`Secondary to Diabetes Mellitus
`
`Resourcelinks provided by NLM:
`
`
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`
`
`GeneticsHomeReferencerelated topics: Xlinkedjuvenileretinoschisis
`
`MedlinePlus related topics: Diabetes Edema
`
`Drug Information available for: Ranibizumab
`
`U.S. EDA Resources
`
`Further study details as provided by Genentech:
`
`Primary Outcome Measures:
`
`« The primary efficacy outcome measureis the proportion of subjects who gain at least 15 letters in BCVA
`compared with baseline [ Time Frame: 24 months] [ Designated as safety issue: No ]
`
`Secondary Outcome Measures:
`
`« Mean changefrom baseline in BCVA score overtime [ Time Frame: 24 months]
`[ Designatedassafety issue: No ]
`¢ Mean change from baseline in central foveal thickness (CFT) over time, as assessed on OCTbythe central
`reading center [ Time Frame: 24 months] [ Designated as safety issue: No ]
`
`https://web.archive.org/web/20100609131649/https:/www.clinicaltrials.gov/ct2/show/NCT00473330
`IPR2023-00884
`Samsung et al. v. Regeneron
`Regeneron Pharmaceuticals, Inc. Exhibit2134
`Page 1
`
`1/4
`
`

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`2/12/24, 9:06 AM
`
`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Dia…
`Proportion of subjects with resolution of leakage at 24 months, as assessed by the central reading center
`using fluorescein angiography (FA) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
`Mean number of macular laser treatments during 24 months [ Time Frame: 24 months ]
`[ Designated as safety issue: No ]
`Mean change from baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25)
`near activities subscale score at 24 months [ Time Frame: 24 months ] [ Designated as safety issue: No ]
`Mean change from baseline in the NEI VFQ-25 distance activities subscale score at 24 months
`[ Time Frame: 24 months ] [ Designated as safety issue: No ]
`Proportion of subjects with a three-step change from baseline in the Early Treatment Diabetic Retinopathy
`Study (ETDRS) scale at 24 months, as assessed by the central reading center using fundus photography
`[ Time Frame: 24 months ] [ Designated as safety issue: No ]
`Mean change from baseline in contrast sensitivity at 24 months, measured by the number of letters read
`correctly on the Pelli-Robson chart [ Time Frame: 24 months ] [ Designated as safety issue: No ]
`Proportion of subjects who gain at least 15 letters in BCVA score compared with baseline at 36 months
`[ Time Frame: 36 months ] [ Designated as safety issue: No ]
`Mean change from baseline in BCVA score over time up to 36 months [ Time Frame: 36 months ]
`[ Designated as safety issue: No ]
`Mean change from baseline in central foveal thickness (CFT) over time up to 36 months, as assessed on
`OCT by the central reading center [ Time Frame: 36 months ] [ Designated as safety issue: No ]
`Mean number of macular laser treatments during 36 months [ Time Frame: 36 months ]
`[ Designated as safety issue: No ]
`Proportion of subjects with a three-step or greater progression from baseline in the ETDRS diabetic
`retinopathy severity level at 36 months, as assessed by the central reading center using FP [ Time Frame: 36
`months ] [ Designated as safety issue: No ]
`Mean change from baseline in contrast sensitivity at 36 months, as measured by the number of letters read
`correctly on the Pelli-Robson chart [ Time Frame: 36 months ] [ Designated as safety issue: No ]
`
`366
`Estimated Enrollment:
`July 2007
`Study Start Date:
`Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
`
`Arms
`1: Experimental
`
`2: Experimental
`
`Assigned Interventions
`Drug: ranibizumab
`Intravitreal injection repeating dose
`
`Drug: ranibizumab
`Intravitreal injection repeating dose
`
`3: Sham Comparator
`
`Drug: sham
`Intravitreal sham injection repeating dose
`
` Eligibility
`
`18 Years and older
`Ages Eligible for Study:
`Both
`Genders Eligible for Study:
`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)
`Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea
`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
`https://web.archive.org/web/20100609131649/https:/www.clinicaltrials.gov/ct2/show/NCT00473330
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`2/4
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`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2134 Page 2
`
`

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`2/12/24, 9:06 AM
`
`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Dia…
`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 (e.g., 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 visit
`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 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 CNV of any cause (e.g., AMD, ocular histoplasmosis, or
`pathologic myopia)
`Concurrent disease in the study eye that would compromise VA 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
`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
`
`Please refer to this study by its ClinicalTrials.gov identifier: NCT00473330
`
`Sponsors and Collaborators
`Genentech
`
`Investigators
`Study Director:
`
`Jason Ehrlich, M.D., Ph.D. Genentech
`
` More Information
`
`No publications provided
`
`Genentech, Inc. ( Clinical Trials Posting Group )
`Responsible Party:
`ClinicalTrials.gov Identifier: NCT00473330 History of Changes
`Other Study ID Numbers:
`FVF4170g
`Study First Received:
`May 13, 2007
`Last Updated:
`November 2, 2009
`Health Authority:
`United States: Food and Drug Administration
`
`Keywords provided by Genentech:
`
`https://web.archive.org/web/20100609131649/https:/www.clinicaltrials.gov/ct2/show/NCT00473330
`
`3/4
`
`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2134 Page 3
`
`

`

`A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Dia…
`
`2/12/24, 9:06 AM
`Lucentis
`DME
`Diabetes
`Vision Loss
`
`Additional relevant MeSH terms:
`Metabolic Diseases
`Immunologic Factors
`Eye Diseases
`Physiological Effects of Drugs
`Diabetes Mellitus
`Edema
`Endocrine System Diseases
`Macular Degeneration
`
`ClinicalTrials.gov processed this record on June 07, 2010
`
`Retinal Degeneration
`Pharmacologic Actions
`Antibodies, Monoclonal
`Macular Edema
`Signs and Symptoms
`Glucose Metabolism Disorders
`Retinal Diseases
`
`Contact Help Desk
`Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine,
`U.S. National Institutes of Health, U.S. Department of Health & Human Services,
`USA.gov, Copyright, Privacy, Accessibility, Freedom of Information Act
`
`
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`
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`https://web.archive.org/web/20100609131649/https:/www.clinicaltrials.gov/ct2/show/NCT00473330
`
`4/4
`
`Samsung et al. v. Regeneron IPR2023-00884
`Regeneron Pharmaceuticals, Inc. Exhibit 2134 Page 4
`
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