Long-Term Efficacy and Safety of Intravitreal Aflibercept Injections for the Treatment of Diabetic Retinopathy for Subjects Who Completed the 2-Year PANORAMA Trial

NCT04708145 | Completed Phase 4 FDA Drug

• 1 other identifier: VOYAGE
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 14

Brief Summary

The VOYAGE trial will assess diabetic retinopathy severity scale (DRSS) levels, through 112 weeks, while being managed with aflibercept as needed, among subjects who completed the 2-year PANORAMA trial (VGFTe-OD-1411) and were treated in a clinical setting prior to joining the VOYAGE study.

Conditions

Diabetic Retinopathy

Outcome Measures

Primary Outcomes (1)

• DRSS Level Achievement in the VOYAGE study

  Proportion of subjects achieving a DRSS level of 43 or less in the VOYAGE study.

  112 weeks

Secondary Outcomes (12)

• DRSS Level Achievement in the PANORAMA study

  112 weeks

• DRSS Level Improvement

  112 weeks

• Injection Frequency

  112 weeks

• Subjects without Treatment

  112 weeks

• PDR Events

  112 weeks

Study Arms (2)

Group 1

EXPERIMENTAL

Study eyes without PRP from the PANORAMA trial. Subjects will be evaluated every 16 weeks and treated if DRSS level is 47 or worse as determined by the treating investigator. Subjects may be evaluated every 8 weeks if a 2-step DRSS level worsening compared to the last protocol-scheduled 16-week visit occurs, the DRSS level is 53 or worse, or if a subject has active PDR. Visits can continue every 8 weeks until there is no active PDR, and the DRSS improves to the level observed at the visit before the subject began being seen at 8-week intervals. Thereafter, visits will continue at 16 week intervals.

Drug: Aflibercept Injection

Group 2

EXPERIMENTAL

Study eyes with PRP from the PANORAMA trial. Subjects will be evaluated every 16 weeks and treated if the neovascular disease process is active and stable (not new or worse) as determined by the treating investigator. If the neovascular disease is inactive, no treatment will be given. If new or worsening neovascularization develops, subjects may be seen and treated every 8 weeks until the neovascular disease is stable or inactive, at which time the interval between visits will increase to 16 weeks.

Drug: Aflibercept Injection

Interventions

Aflibercept Injection DRUG

Intravitreal 2mg aflibercept injection

Also known as: Eylea

Group 1; Group 2

Eligibility Criteria

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

You may qualify if:

• Enrolled and completed PANORAMA (VGFTe-OD-1411) clinical trial
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent

You may not qualify if:

• Any prior systemic anti-vascular endothelial growth factor (VEGF) treatment or IVT anti-VEGF treatment in the study eye within 21 days of baseline
• Any intra- or periocular corticosteroid treatment in the study eye within 3 months of baseline
• Any intraocular sustained-release treatment, implantable device, or gene therapy in the study eye
• Pregnant or breastfeeding women
• Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening/baseline; intrauterine device (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly).
• Contraception is not required for men with documented vasectomy. \*\*Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Sponsors & Collaborators

• Greater Houston Retina Research: lead
• Regeneron Pharmaceuticals: collaborator
• Clinical Trials Resource Group, LLC: collaborator

Study Sites (14)

Retina Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Central Florida Retina Center

Orlando, Florida, 32806, United States

Location

Center for Retina and Macular Disease

Winter Haven, Florida, 33880, United States

Location

Marietta Eye Clinic

Marietta, Georgia, 30060, United States

Location

John Kenyon American Eye Institute

New Albany, Indiana, 47150, United States

Location

Cumberland Valley Retina Consultants, P.C.

Hagerstown, Maryland, 21740, United States

Location

Dean McGee Eye Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Palmetto Retina Center, LLC - Florence

Florence, South Carolina, 29501, United States

Location

Palmetto Retina Center

West Columbia, South Carolina, 29169, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Valley Retina Institute

Harlingen, Texas, 78550, United States

Location

Strategic Clinical Research Group, LLC

Willow Park, Texas, 76087, United States

Location

Emanuelli Research and Development Center, LLC

Arecibo, 00613, Puerto Rico

Location

Related Publications (23)

• Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.

  PMID: 15078674 BACKGROUND

• Leasher JL, Bourne RR, Flaxman SR, Jonas JB, Keeffe J, Naidoo K, Pesudovs K, Price H, White RA, Wong TY, Resnikoff S, Taylor HR; Vision Loss Expert Group of the Global Burden of Disease Study. Global Estimates on the Number of People Blind or Visually Impaired by Diabetic Retinopathy: A Meta-analysis From 1990 to 2010. Diabetes Care. 2016 Sep;39(9):1643-9. doi: 10.2337/dc15-2171.

  PMID: 27555623 BACKGROUND

• Bourne RR, Stevens GA, White RA, Smith JL, Flaxman SR, Price H, Jonas JB, Keeffe J, Leasher J, Naidoo K, Pesudovs K, Resnikoff S, Taylor HR; Vision Loss Expert Group. Causes of vision loss worldwide, 1990-2010: a systematic analysis. Lancet Glob Health. 2013 Dec;1(6):e339-49. doi: 10.1016/S2214-109X(13)70113-X. Epub 2013 Nov 11.

  PMID: 25104599 BACKGROUND

• Fong DS, Girach A, Boney A. Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: a literature review. Retina. 2007 Sep;27(7):816-24. doi: 10.1097/IAE.0b013e318042d32c.

  PMID: 17891003 BACKGROUND

• Ferris F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc. 1996;94:505-37.

  PMID: 8981711 BACKGROUND

• Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

  PMID: 20427088 BACKGROUND

• Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.

  PMID: 22330964 BACKGROUND

• Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, Midena E, Kaiser PK, Terasaki H, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Brown DM. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014 Nov;121(11):2247-54. doi: 10.1016/j.ophtha.2014.05.006. Epub 2014 Jul 8.

  PMID: 25012934 BACKGROUND

• Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.

  PMID: 26565927 BACKGROUND

• Diabetic Retinopathy Clinical Research Network; Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, Antoszyk AN, Arnold-Bush B, Baker CW, Bressler NM, Browning DJ, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015 Mar 26;372(13):1193-203. doi: 10.1056/NEJMoa1414264. Epub 2015 Feb 18.

  PMID: 25692915 BACKGROUND

• Sivaprasad S, Prevost AT, Vasconcelos JC, Riddell A, Murphy C, Kelly J, Bainbridge J, Tudor-Edwards R, Hopkins D, Hykin P; CLARITY Study Group. Clinical efficacy of intravitreal aflibercept versus panretinal photocoagulation for best corrected visual acuity in patients with proliferative diabetic retinopathy at 52 weeks (CLARITY): a multicentre, single-blinded, randomised, controlled, phase 2b, non-inferiority trial. Lancet. 2017 Jun 3;389(10085):2193-2203. doi: 10.1016/S0140-6736(17)31193-5. Epub 2017 May 7.

  PMID: 28494920 BACKGROUND

• Mazhar K, Varma R, Choudhury F, McKean-Cowdin R, Shtir CJ, Azen SP; Los Angeles Latino Eye Study Group. Severity of diabetic retinopathy and health-related quality of life: the Los Angeles Latino Eye Study. Ophthalmology. 2011 Apr;118(4):649-55. doi: 10.1016/j.ophtha.2010.08.003. Epub 2010 Oct 29.

  PMID: 21035872 BACKGROUND

• Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-five-year incidence of macular edema in persons with type 1 diabetes. Ophthalmology. 2009 Mar;116(3):497-503. doi: 10.1016/j.ophtha.2008.10.016. Epub 2009 Jan 22.

  PMID: 19167079 BACKGROUND

• Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):823-33.

  PMID: 2062515 BACKGROUND

• Klein R, Klein BE, Moss SE. How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy. Arch Ophthalmol. 2001 Apr;119(4):547-53. doi: 10.1001/archopht.119.4.547.

  PMID: 11296020 BACKGROUND

• Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, Dills D, Kampik A, Pararajasegaram R, Verdaguer JT; Global Diabetic Retinopathy Project Group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003 Sep;110(9):1677-82. doi: 10.1016/S0161-6420(03)00475-5.

  PMID: 13129861 BACKGROUND

• Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, Heier JS, Terasaki H, Kaiser PK, Marcus DM, Nguyen QD, Jaffe GJ, Slakter JS, Simader C, Soo Y, Schmelter T, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Zeitz O, Metzig C, Korobelnik JF. Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the VISTA and VIVID Studies. Ophthalmology. 2015 Oct;122(10):2044-52. doi: 10.1016/j.ophtha.2015.06.017. Epub 2015 Jul 18.

  PMID: 26198808 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Ip MS, Domalpally A, Sun JK, Ehrlich JS. Long-term effects of therapy with ranibizumab on diabetic retinopathy severity and baseline risk factors for worsening retinopathy. Ophthalmology. 2015 Feb;122(2):367-74. doi: 10.1016/j.ophtha.2014.08.048. Epub 2014 Nov 18.

  PMID: 25439595 BACKGROUND

• Bressler SB, Liu D, Glassman AR, Blodi BA, Castellarin AA, Jampol LM, Kaufman PL, Melia M, Singh H, Wells JA; Diabetic Retinopathy Clinical Research Network. Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. JAMA Ophthalmol. 2017 Jun 1;135(6):558-568. doi: 10.1001/jamaophthalmol.2017.0821.

  PMID: 28448655 BACKGROUND

• Wykoff CC, Le RT, Khurana RN, Brown DM, Ou WC, Wang R, Clark WL, Boyer DS; ENDURANCE Study Group. Outcomes With As-Needed Aflibercept and Macular Laser Following the Phase III VISTA DME Trial: ENDURANCE 12-Month Extension Study. Am J Ophthalmol. 2017 Jan;173:56-63. doi: 10.1016/j.ajo.2016.09.029. Epub 2016 Oct 1.

  PMID: 27702624 BACKGROUND

• Zhou AW, Teagle GM, Baumann LM, Cao JA, Emanuelli A, Hu AY, Berger AS, Major JC Jr, Lee SY, Huddleston SM, Gonzalez VH, Clark WL, Liao DS, Kingsley RM, Lazarus HS, Payne JF, Feinstein EG, Meleth AD, Patel SB, Fan KC, Berliner AJ, Moini H, Niu X, Ip MS, Sadda SR, Al-Khersan H, Wykoff CC. Intravitreal Aflibercept for the Treatment of Diabetic Retinopathy Among Patients Who Completed PANORAMA: 1-Year Outcomes from the VOYAGE Extension Study. J Pers Med. 2025 Nov 14;15(11):555. doi: 10.3390/jpm15110555.

  PMID: 41295257 DERIVED

Related Links

• World Health Organization (WHO). Global Report on Diabetes. 2016.
• Study of the Efficacy and Safety of Intravitreal (IVT) Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (NPDR) (PANORAMA)

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 13, 2021
• Study Start: June 1, 2021
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); PR (1)