A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RISE)

NCT00473330 | Completed Phase 3 Results

• 1 other identifier: FVF4170g
• Study Type: interventional
• Target: 377
• Locations: 0 countries
• Sites: N/A

Brief Summary

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 NCT00473382 (Protocol ID FVF4168g). The open-label extension phase of the study was stopped after receiving FDA approval of the study drug (ranibizumab) for diabetic macular edema.

Conditions

Diabetes Mellitus; Macular Edema

Keywords

Lucentis; DME; Diabetes; Vision loss

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Gained ≥ 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at 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.

  Baseline to Month 24

Secondary Outcomes (12)

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24, 36, and 48

  Baseline to Month 48

• Percentage of Patients With a Visual Acuity (VA) Snellen Equivalent of 20/40 or Better at Months 24, 36, and 48

  Months 24, 36, and 48

• Percentage of Patients Who Lost < 15 Letters in Their Best Corrected Visual Acuity (BCVA) Score From Baseline at Months 24, 36, and 48

  Baseline to Month 48

• Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Months 24 and 36 in Patients With Focal Edema at Baseline

  Baseline to Month 36

• Mean Change From Baseline in Central Foveal Thickness at Months 24, 36, and 48

  Baseline to Month 48

Study Arms (3)

Ranibizumab 0.3 mg

EXPERIMENTAL

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.

Drug: Ranibizumab

Ranibizumab 0.5 mg

EXPERIMENTAL

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.

Drug: Ranibizumab

Sham injection/ranibizumab 0.5 mg

SHAM COMPARATOR

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.

Drug: Sham injection

Interventions

Ranibizumab DRUG

Sterile solution for intravitreal injection.

Also known as: Lucentis

Ranibizumab 0.3 mg; Ranibizumab 0.5 mg

Sham injection DRUG

Sham injection/ranibizumab 0.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (19)

• Bressler N, Haskova Z, Kapre A, Gentile B. Clinically Meaningful Change Estimates for the National Eye Institute Visual Function Questionnaire-25 in Patients With Diabetic Macular Edema. Transl Vis Sci Technol. 2024 Dec 2;13(12):27. doi: 10.1167/tvst.13.12.27.

  PMID: 39680390 DERIVED

• Stockwell AD, Chang MC, Mahajan A, Forrest W, Anegondi N, Pendergrass RK, Selvaraj S, Reeder J, Wei E, Iglesias VA, Creps NM, Macri L, Neeranjan AN, van der Brug MP, Scales SJ, McCarthy MI, Yaspan BL. Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema. PLoS Genet. 2023 Aug 16;19(8):e1010609. doi: 10.1371/journal.pgen.1010609. eCollection 2023 Aug.

  PMID: 37585454 DERIVED

• Talcott KE, Valentim CCS, Hill L, Stoilov I, Singh RP. Baseline Diabetic Retinopathy Severity and Time to Diabetic Macular Edema Resolution with Ranibizumab Treatment: A Meta-Analysis. Ophthalmol Retina. 2023 Jul;7(7):605-611. doi: 10.1016/j.oret.2023.02.003. Epub 2023 Feb 10.

  PMID: 36774994 DERIVED

• Goldberg RA, Hill L, Davis T, Stoilov I. Effect of less aggressive treatment on diabetic retinopathy severity scale scores: analyses of the RIDE and RISE open-label extension. BMJ Open Ophthalmol. 2022 Jul;7(1):e001007. doi: 10.1136/bmjophth-2022-001007.

  PMID: 36161830 DERIVED

• Singer M, Liu M, Schlottmann PG, Khanani AM, Hemphill M, Hill L, Tuomi L, Haskova Z. Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials. Clin Ophthalmol. 2020 Jun 17;14:1629-1639. doi: 10.2147/OPTH.S247061. eCollection 2020.

  PMID: 32606578 DERIVED

• 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.

  PMID: 31668888 DERIVED

• 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.

  PMID: 31047503 DERIVED

• 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.

  PMID: 31047350 DERIVED

• 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.

  PMID: 30419298 DERIVED

• 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.

  PMID: 29752001 DERIVED

• 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.

  PMID: 27234930 DERIVED

• 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.

  PMID: 26992841 DERIVED

• Bressler NM, Varma R, Mitchell P, Suner 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.

  PMID: 26584450 DERIVED

• 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.

  PMID: 26452713 DERIVED

• 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.

  PMID: 26050541 DERIVED

• Bressler NM, Varma R, Suner 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 RIDE and RISE. Ophthalmology. 2014 Dec;121(12):2461-72. doi: 10.1016/j.ophtha.2014.07.008. Epub 2014 Aug 20.

  PMID: 25148789 DERIVED

• 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.

  PMID: 24768239 DERIVED

• 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.

  PMID: 23706949 DERIVED

• 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.

  PMID: 22965590 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Macular Edema; Vision Disorders

Interventions

Ranibizumab; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Genentech, Inc.

genentech@druginfo.com

800 821-8590

Study Officials

• Jason Ehrlich, M.D., Ph.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2007
• First Posted: May 15, 2007
• Study Start: June 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2012
• Last Updated: April 17, 2017
• Results First Posted: January 17, 2013

Record last verified: 2017-03