AzTrials
AzTrials

Diabetic RetinopathyPhase 4VOYAGENCT04708145

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

A Phase 4 study testing Aflibercept Injection in people with Diabetic Retinopathy, run by Greater Houston Retina Research at 14 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Retinopathy
What is being tested?
Aflibercept Injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
14 sitesin 2 countries
Study dates
1 Jun 2021to 31 Jul 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

United States13 sites
  • Retina Consultants of Texas

    Bellaire, Texas, 77401

  • Retina Vitreous Associates Medical Group

    Beverly Hills, California, 90211

  • Palmetto Retina Center, LLC - Florence

    Florence, South Carolina, 29501

  • Charles Retina Institute

    Germantown, Tennessee, 38138

  • Cumberland Valley Retina Consultants, P.C.

    Hagerstown, Maryland, 21740

  • Valley Retina Institute

    Harlingen, Texas, 78550

  • Marietta Eye Clinic

    Marietta, Georgia, 30060

  • John Kenyon American Eye Institute

    New Albany, Indiana, 47150

  • Dean McGee Eye Institute

    Oklahoma City, Oklahoma, 73104

  • Central Florida Retina Center

    Orlando, Florida, 32806

  • Palmetto Retina Center

    West Columbia, South Carolina, 29169

  • Strategic Clinical Research Group, LLC

    Willow Park, Texas, 76087

  • Center for Retina and Macular Disease

    Winter Haven, Florida, 33880

Other trials in United States

Puerto Rico1 site
  • Emanuelli Research and Development Center, LLC

    Arecibo, 00613

Other trials in Puerto Rico

About this study

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.

Read the detailed description

This phase 4 study is designed to assess the need for ongoing 2 mg intravitreal aflibercept injections (IAI) for subjects who completed the 2-year PANORAMA (VGFTe-OD-1411) trial for the management of diabetic retinopathy (DR). Sites will be considered for VOYAGE if they have 4 or more subjects from PANORAMA able to participate.

Relevant data from all participating subjects will be collected and reported retrospectively for the period between PANORAMA study exit and VOYAGE study enrollment.

For the prospective portion of the study, eyes will be assigned to 1 of 2 groups, eyes without panretinal photocoagulation (PRP) and eyes with PRP.

Group 1: Subjects with study eyes without PRP will be seen every 16 weeks (Q16W) and treated with IAI on a flexible treatment regimen based on their DRSS level. An injection will be given at each 16-week visit when the DRSS level is 47 or worse. If the DRSS level is better than 47, for example level 43 or 35, the study eye will not be treated. DRSS level will be determined by the investigator, based on ophthalmic exam and fundus photography (FP) compared to prior imaging when available.

Every 8 week visits can be performed under specific circumstances:

  • If a subject has a 2-step DRSS level worsening compared to the last protocol-scheduled 16-week visit (for example the week-16 or week-32 visit) and/or the DRSS level is 53 or worse OR
  • If a subject has active proliferative DR (PDR)

Under both of these circumstances, IAI will be administered as scheduled and the subject can be seen and treated every 8 weeks (Q8W) with IAI. Under both of these circumstances, Q8W visits and Q8W IAI treatments can be continued 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.

Group 2: Subjects with study eyes with PRP will be seen Q16W and treated with IAI on a flexible treatment regimen based on activity of the neovascular disease process as assessed by the treating investigator based on ophthalmic exam and/or FP compared to prior imaging when available. If the neovascular disease is inactive, no treatment will be given. If the neovascular disease is active and stable (not new or worse), the subject will be treated with intravitreal (IVT) IAI at the Q16W interval. If new or worsening neovascular disease develops, subjects may be seen and treated Q8W until the neovascular disease is stable or inactive at which time the interval between visits will increase to 16 weeks.

Subjects in both groups will be evaluated for efficacy, using best corrected visual acuity (BCVA) using the 4-meter ETDRS protocol with normal-luminance, Humphrey Visual Field (HVF), National Eye Institute (NEI) Visual Function Questionnaire (VFQ) 25, spectral domain optical coherence tomography (SD-OCT), optical coherence tomography angiography (OCT-A), FP, and fluorescein angiography (FA), and for ocular and systemic safety (including ophthalmic exams and laboratory assessments) through week 112.

Subjects who develop new or worsening PDR, including anterior segment neovascularization (ASNV), or center-involved DME may qualify for rescue treatment.

Being tested
Aflibercept Injection
Medical subject headings
Diabetic Retinopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aflibercept InjectionDrug

    Also called Eylea

    Intravitreal 2mg aflibercept injection

Study groups in NCT04708145
Study groupRoleWhat they receive
Group 1ExperimentalStudy 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.
Receives: Drug: Aflibercept Injection
Group 2ExperimentalStudy 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.
Receives: Drug: Aflibercept Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DRSS Level Achievement in the VOYAGE study

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

    Measured: 112 weeks

Secondary outcomes (12)
  1. DRSS Level Achievement in the PANORAMA study

    Proportion of subjects achieving a DRSS level of 43 or less from the completion of the PANORAMA study

    Measured: 112 weeks

  2. DRSS Level Improvement

    Proportion of subjects with stable, worsened, or improved DRSS level from baseline to week 48 and baseline to week 112 compared to the DRSS at the baseline of the VOYAGE trial and the DRSS at the last visit of the PANORAMA trial.

    Measured: 112 weeks

  3. Injection Frequency

    Mean and median number of IVT aflibercept injections (with and without IAI given for DME)

    Measured: 112 weeks

  4. Subjects without Treatment

    Proportion of subjects receiving 0 injections

    Measured: 112 weeks

  5. PDR Events

    Percentage of subjects over time who develop a new PDR event

    Measured: 112 weeks

  6. Center-Involved Diabetic Macular Edema Development

    Percentage of subjects over time who develop center-involved (CI) DME

    Measured: 112 weeks

  7. Change in Visual Acuity

    Mean change in ETDRS BCVA from baseline

    Measured: 112 weeks

  8. Change in Central Retinal Thickness

    Mean change in central retinal thickness from baseline

    Measured: 112 weeks

  9. Change in Area of Nonperfusion

    Change in total area of retinal capillary non-perfusion from baseline

    Measured: 112 weeks

  10. Changes in Visual Function (HVF)

    Changes in visual function outcomes from Humphrey Visual Field from baseline

    Measured: 112 weeks

  11. Changes in Visual Function

    Changes in visual function outcomes NEI VFQ-25 from baseline

    Measured: 112 weeks

  12. Incidence of Adverse Events

    Incidence and severity of ocular and systemic adverse events from baseline

    Measured: 112 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2021
  2. Study start1 Jun 2021
  3. Primary completion31 Jul 2024
  4. Study completion31 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04708145
Sponsor's protocol ID
VOYAGE
Acronym
VOYAGE
Status last verified
Jan 2025
First submitted
6 Jan 2021
Last updated
23 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 15078674
  • 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.

    PubMed 27555623
  • 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.

    PubMed 25104599
  • 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.

    PubMed 17891003
  • Ferris F. Early photocoagulation in patients with either type I or type II diabetes. Trans Am Ophthalmol Soc. 1996;94:505-37.

    PubMed 8981711
  • 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.

    PubMed 20427088
  • 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.

    PubMed 22330964
  • 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.

    PubMed 25012934
  • 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.

    PubMed 26565927
  • 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.

    PubMed 25692915
  • 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.

    PubMed 28494920
  • 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.

    PubMed 21035872
  • 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.

    PubMed 19167079
  • 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.

    PubMed 2062515
  • 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.

    PubMed 11296020

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Aflibercept Injection in people with Diabetic Retinopathy, run by Greater Houston Retina Research at 14 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DRSS Level Achievement in the VOYAGE study (time frame: 112 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04708145, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in