Intravitreal Aflibercept Injection for Radiation Retinopathy Trial

NCT03085784 | Unknown Phase 2 FDA Drug

• 1 other identifier: ARRT
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The ARRT trial will assess the safety and efficacy of 2mg aflibercept for the treatment of radiation retinopathy, including maculopathy and optic neuropathy over 52 weeks.

Conditions

Radiation Retinopathy

Outcome Measures

Primary Outcomes (1)

• Safety of intravitreal Aflibercept for the treatment of radiation retinopathy - Assessed by incidence of adverse events.

  The primary objective of the study is to assess the safety of 2 mg intravitreal Aflibercept injections (IAI) for the treatment of radiation retinopathy including maculopathy and optic neuropathy. Assessed by incidence of adverse events.

  52 Weeks

Secondary Outcomes (6)

• Resolution of macular edema (CRT)

  52 Weeks

• Resolution of macular edema (% dry)

  52 Weeks

• Stabilization and improvement in visual acuity

  52 Weeks

• Dosing frequency of intravitreal aflibercept injections

  52 Weeks

• Incidence of neovascularization, vitreous hemorrhage, and need for vitrectomy

  52 Weeks

Study Arms (2)

Loading Dose

EXPERIMENTAL

20 Patients will receive 4, 2 mg IVT Aflibercept (IAI) a month apart, screening/baseline, weeks 4, 8, \& 12. At week 12, patient will be followed \& treated per treat \& extend protocol. Treat \& Extend Protocol entails patients being extended as long as: * Absence of retinal fluid (resolution of intraretinal \& subretinal fluid on SD-OCT; Small intraretinal cysts that don't distort foveal contour on SD-OCT are acceptable \& can be considered "dry".) AND * \< 5 ETDRS letter loss from previous visit, due to new or persistent retinal edema. Each extension will be 2 weeks in duration beyond the initial 4-week interval. If the extension criteria are not met on a follow-up visit, treatment interval will be reduced by 2 weeks. Follow up interval will continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval is reached.

Drug: Aflibercept

Treat and Extend

EXPERIMENTAL

20 Patients will receive 2 mg IVT Aflibercept (IAI) at screening/baseline followed by a visit at week 4. At week 4, patient will be treated \& followed per the treat \& extend protocol. Treat \& Extend Protocol entails patients being extended as long as: * Absence of retinal fluid (resolution of intraretinal \& subretinal fluid on SD-OCT; Small intraretinal cysts that don't distort foveal contour on SD-OCT are acceptable \& can be considered "dry".) AND * \< 5 ETDRS letter loss from previous visit, due to new or persistent retinal edema. Each extension will be 2 weeks in duration beyond the initial 4-week interval. If the extension criteria are not met on a follow-up visit, treatment interval will be reduced by 2 weeks. Follow up interval will continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval is reached.

Drug: Aflibercept

Interventions

Aflibercept DRUG

The investigational product is intravitreal aflibercept injection (IAI), which will be supplied by Regeneron Pharmaceuticals, Inc. in sterile vials for intravitreal (IVT) injection. The study duration will be 52 weeks. Vials of drug must be used (defined as entered with needle) only once. All drug supplies are to be kept under recommended storage conditions. The injection volume will be 50μL (0.05 mL) and will be administered to the patients by IVT injection.

Also known as: Eylea

Loading Dose; Treat and Extend

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years of age
• Clinically identifiable radiation retinopathy with evidence of fluid on SD-OCT causing vision loss in the study eye
• Undergone either ocular or orbital radiation for any primary ocular or orbital cancer within clinical evidence of having radiation retinopathy
• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent

You may not qualify if:

• A patient who meets any of the following criteria will be excluded from the study:
• Metastatic cancer or any active primary cancer, at time of enrollment
• Prior treatment with anti VEGF in the study within 60 days of screen in the study eye
• Prior intravitreal or subconjunctival treatment with cortical steroids within 90 days of screen in the study eye
• Macular ischemia (defined as greater than 5 disc areas), as assessed by the investigator
• Media opacity obscuring a view of the fundus or any other reason for vision loss other than radiation retinopathy.
• Evidence of infectious ocular infection, in the study eye, at time of screening
• Pregnant or breast-feeding women
• Sexually active men\* or women of childbearing potential\*\* who are unwilling to practice adequate contraception start of the first treatment, during the study, and for at least 3 months after the last dose. 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; 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 amenorrheic 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

• Amy C Schefler, MD: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (3)

Retina Consultants of Houston/Texas Medical Center

Houston, Texas, 77030, United States

Location

Retina Consultants of Houston

Katy, Texas, 77494, United States

Location

Retina Consultants of Houston/The Woodlands

The Woodlands, Texas, 77384, United States

Location

Related Publications (12)

• Jampol LM, Moy CS, Murray TG, Reynolds SM, Albert DM, Schachat AP, Diddie KR, Engstrom RE Jr, Finger PT, Hovland KR, Joffe L, Olsen KR, Wells CG; Collaborative Ocular Melanoma Study Group (COMS Group). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology. 2002 Dec;109(12):2197-206. doi: 10.1016/s0161-6420(02)01277-0.

  PMID: 12466159 BACKGROUND

• Melia BM, Abramson DH, Albert DM, Boldt HC, Earle JD, Hanson WF, Montague P, Moy CS, Schachat AP, Simpson ER, Straatsma BR, Vine AK, Weingeist TA; Collaborative Ocular Melanoma Study Group. Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16. Ophthalmology. 2001 Feb;108(2):348-66. doi: 10.1016/s0161-6420(00)00526-1.

  PMID: 11158813 BACKGROUND

• Gunduz K, Shields CL, Shields JA, Cater J, Freire JE, Brady LW. Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Arch Ophthalmol. 1999 May;117(5):609-14. doi: 10.1001/archopht.117.5.609.

  PMID: 10326957 BACKGROUND

• Finger PT, Chin KJ. High-dose (2.0 mg) intravitreal ranibizumab for recalcitrant radiation retinopathy. Eur J Ophthalmol. 2013 Nov-Dec;23(6):850-6. doi: 10.5301/ejo.5000333. Epub 2013 Jun 28.

  PMID: 23813109 BACKGROUND

• Finger PT, Chin KJ. Intravitreous ranibizumab (lucentis) for radiation maculopathy. Arch Ophthalmol. 2010 Feb;128(2):249-52. doi: 10.1001/archophthalmol.2009.376. No abstract available.

  PMID: 20142553 BACKGROUND

• Finger PT, Chin KJ. Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy. Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27.

  PMID: 21277107 BACKGROUND

• Finger PT, Mukkamala SK. Intravitreal anti-VEGF bevacizumab (Avastin) for external beam related radiation retinopathy. Eur J Ophthalmol. 2011 Jul-Aug;21(4):446-51. doi: 10.5301/EJO.2011.6213.

  PMID: 21218391 BACKGROUND

• Mason JO 3rd, Albert MA Jr, Persaud TO, Vail RS. Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma. Retina. 2007 Sep;27(7):903-7. doi: 10.1097/IAE.0b013e31806e6042.

  PMID: 17891015 BACKGROUND

• Finger PT. Radiation retinopathy is treatable with anti-vascular endothelial growth factor bevacizumab (Avastin). Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):974-7. doi: 10.1016/j.ijrobp.2007.11.045.

  PMID: 18313522 BACKGROUND

• Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (avastin) for radiation retinopathy. Arch Ophthalmol. 2007 Jun;125(6):751-6. doi: 10.1001/archopht.125.6.751.

  PMID: 17562985 BACKGROUND

• Gupta A, Muecke JS. Treatment of radiation maculopathy with intravitreal injection of bevacizumab (Avastin). Retina. 2008 Jul-Aug;28(7):964-8. doi: 10.1097/IAE.0b013e3181706302.

  PMID: 18698298 BACKGROUND

• Kim IK, Lane AM, Jain P, Awh C, Gragoudas ES. Ranibizumab for the Prevention of Radiation Complications in Patients Treated With Proton Beam Irradiation for Choroidal Melanoma. Trans Am Ophthalmol Soc. 2016 Aug;114:T2.

  PMID: 27630373 BACKGROUND

MeSH Terms

Interventions

aflibercept

Study Officials

• Amy C Schefler, MD

  Retina Consultants Houston

  PRINCIPAL INVESTIGATOR

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: March 15, 2017
• First Posted: March 21, 2017
• Study Start: July 5, 2017
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: December 8, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)