Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy

NCT02863354 | Completed Phase 2 Results

• 1 other identifier: RECOVERY
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief Summary

The RECOVERY trial will assess the safety and tolerability of 2 mg intravitreal aflibercept injections (IAI) given monthly (Q4WK) or every 12 weeks (Q12WK) for the treatment of retinal capillary non-perfusion (RNP) associated with proliferative diabetic retinopathy (PDR).

• Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52
• Change in area of retinal capillary non-perfusion, as assessed by central reading center, from baseline through week 52

Conditions

Proliferative Diabetic Retinopathy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  • Assess the safety and tolerability of IAI for the treatment of proliferative diabetic retinopathy by evaluating the incidence and severity of ocular and systemic adverse events through week 52 and week 100.

  52 and 100 weeks

Secondary Outcomes (11)

• Change in Early Treatment of Diabetic Retinopathy Severity Best Corrected Visual Acuity

  52 weeks and 100 weeks

• Change in Area of Retinal Capillary Non-perfusion Within the Macula

  52 weeks and 100 weeks

• Change in Area of Retinal Capillary Non-perfusion Outside of the Macula

  52 weeks and 100 weeks

• Percentage of Subjects With Neovascularization Regression

  52 Weeks and 100 Weeks

• Percentage of Subjects With Increased Neovascularization

  52 Weeks and 100 Weeks

Study Arms (2)

Q4WKS

EXPERIMENTAL

Aflibercept 2 mg every 4 weeks (defined as every 28 days (+ 7 days) and at least 21 days between injections) through week 48. Following week 48, aflibercept 2 mg every 12 weeks through week 96. If NV or PDR are worse per pre-specified criteria at week 60, or at any study visit thereafter, the subject will be treated every 4 weeks through the end of the study.

Drug: Aflibercept

Q12WKS

EXPERIMENTAL

Aflibercept 2 mg every 12-weeks. Subjects will be followed every 4 weeks through week 12, and can be treated if the pre-specified criteria are met. Starting at week 12 if NV or PDR are stable or improved (as assessed by investigator) the subject will be monitored and treated at a 12-week interval through week 48. If NV or PDR are worse per the pre-specified criteria at week 12, or at any study visit thereafter, the subject will be treated monthly through the end of the study. At week 52, aflibercept 2 mg every 4 weeks (defined as 28 days (+ 7 days) and at least 21 days between injections) for subjects with visible retinal non-perfusion. If retinal non-perfusion has completely resolved at week 72, aflibercept every 12 weeks through end of study. For subjects without retinal non-perfusion at week 52, aflibercept 2 mg every 12 weeks through the end of study.

Drug: Aflibercept

Interventions

Aflibercept DRUG

Intravitreal injection

Also known as: Eylea

Q12WKS; Q4WKS

Eligibility Criteria

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

You may qualify if:

• Type 1 or type 2 diabetes mellitus
• BCVA ETDRS \> 20/400 in the study eye
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent
• Substantial non perfusion (defined as greater than 20 disc areas), as assessed by the investigator
• Early PDR, as assessed by the investigator, with no vitreous hemorrhage\*
• Early PDR is defined in which PRP can safely be deferred and vitreous hemorrhage that does not obscure the application of PRP

You may not qualify if:

• Any prior systemic anti-VEGF (anti vascular endothelial growth factor) or IVT anti-VEGF treatment in the study eye,
• SD-OCT (Spectral Domain Optical Coherence Tomography) central subfield thickness measurement of \> 320 µm, in the study eye
• Evidence of infectious ocular infection, in the study eye, at time of screening
• History of vitreoretinal surgery in the study eye
• Any prior Panretinal laser photocoagulation (PRP) in the study eye
• Current vitreous hemorrhage obscuring retinal imaging in the study eye
• Cataract surgery in the study eye within 4 weeks of Day 0
• Uncontrolled blood pressure (defined as \> 180/110 mm Hg systolic/diastolic, while seated)
• Significant renal disease defined as a history of chronic renal failure requiring dialysis or renal transplant
• Tractional Retinal Detachment threatening the macula in the study eye
• Corticosteroid treatment (intravitreal or peribulbar) in the study eye within 12 weeks of screening
• Pregnant or breast-feeding 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; 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.

Sponsors & Collaborators

• Charles C Wykoff, PhD, MD: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (4)

Retina Consultants of Houston/The Medical Center

Houston, Texas, 77030, United States

Location

Retina Consultants of Houston/Katy office

Katy, Texas, 77494, United States

Location

Retina Consultants of Houston

Kingwood, Texas, 77339, United States

Location

Retina Consultants of Houston

The Woodlands, Texas, 77384, United States

Location

Related Publications (16)

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  PMID: 15078674 BACKGROUND

• Klein R, Klein BE, Moss SE. A population-based study of diabetic retinopathy in insulin-using patients diagnosed before 30 years of age. Diabetes Care. 1985 Sep-Oct;8 Suppl 1:71-6. doi: 10.2337/diacare.8.1.s71.

  PMID: 4053957 BACKGROUND

• Preliminary report on effects of photocoagulation therapy. The Diabetic Retinopathy Study Research Group. Am J Ophthalmol. 1976 Apr;81(4):383-96. doi: 10.1016/0002-9394(76)90292-0.

  PMID: 944535 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

• Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981 Jul;88(7):583-600.

  PMID: 7196564 BACKGROUND

• Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

  PMID: 2062512 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

• Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. doi: 10.1056/NEJM199412013312203.

  PMID: 7526212 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

• 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

• Campochiaro PA, Wykoff CC, Singer M, Johnson R, Marcus D, Yau L, Sternberg G. Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion: the SHORE study. Ophthalmology. 2014 Dec;121(12):2432-42. doi: 10.1016/j.ophtha.2014.06.011. Epub 2014 Jul 21.

  PMID: 25060610 BACKGROUND

• Heier J. The Effect of Intravitreal Aflibercept on Capillary Non-perfusion in Patients with Proliferative Retinopathy and/or Macular Edema Secondary to Proliferative Diabetic Retinopathy and Central Retinal Venous Occlusive Disease (ANDROID Study). Retina Society, Paris, France. 2015.

  BACKGROUND

• Babiuch A, Wykoff CC, Hach J, Srivastava S, Talcott KE, Yu HJ, Nittala M, Sadda S, Ip MS, Le T, Hu M, Reese J, Ehlers JP. Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study. Br J Ophthalmol. 2021 Aug;105(8):1111-1115. doi: 10.1136/bjophthalmol-2020-316952. Epub 2020 Aug 22.

  PMID: 32829304 DERIVED

• Alagorie AR, Nittala MG, Velaga S, Zhou B, Rusakevich AM, Wykoff CC, Sadda SR. Association of Intravitreal Aflibercept With Optical Coherence Tomography Angiography Vessel Density in Patients With Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Aug 1;138(8):851-857. doi: 10.1001/jamaophthalmol.2020.2130.

  PMID: 32584384 DERIVED

• Babiuch AS, Wykoff CC, Srivastava SK, Talcott K, Zhou B, Hach J, Hu M, Reese JL, Ehlers JP. RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY. Retina. 2020 Nov;40(11):2175-2183. doi: 10.1097/IAE.0000000000002727.

  PMID: 31917731 DERIVED

MeSH Terms

Interventions

aflibercept

Results Point of Contact

• Title: Dr. Charles C. Wykoff
• Organization: Retina Consultants of Houston

ccwmd@houstonretina.com

713-524-3434

Study Officials

• Charles C Wykoff, PhD, MD

  Retina Consultants Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 11, 2016
• Study Start: August 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: May 24, 2021
• Results First Posted: April 21, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)