Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intravitreal Aflibercept Injection for Radiation Retinopathy Trial (ARRT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03085784
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : May 15, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Amy C Schefler, MD, Greater Houston Retina Research

Tracking Information
First Submitted Date  ICMJE March 15, 2017
First Posted Date  ICMJE March 21, 2017
Last Update Posted Date May 15, 2018
Actual Study Start Date  ICMJE July 5, 2017
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2017)
Safety of intravitreal Aflibercept for the treatment of radiation retinopathy - Assessed by incidence of adverse events. [ Time Frame: 52 Weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03085784 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2017)
  • Resolution of macular edema (CRT) [ Time Frame: 52 Weeks ]
    Resolution of macular edema as measured by mean change in central retinal thickness
  • Resolution of macular edema (% dry) [ Time Frame: 52 Weeks ]
    Resolution of macular edema as measured by % of patients who achieve a dry macula
  • Stabilization and improvement in visual acuity [ Time Frame: 52 Weeks ]
    Stabilization and improvement in visual acuity as measured by the mean change in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity
  • Dosing frequency of intravitreal aflibercept injections [ Time Frame: 52 Weeks ]
    Dosing frequency of IAI as measured by number of injections
  • Incidence of neovascularization, vitreous hemorrhage, and need for vitrectomy [ Time Frame: 52 Weeks ]
    Percentage of patients avoiding the development of increased neovascularization, vitreous hemorrhage, and need for vitrectomy
  • Resolution of retinal hemorrhage, retinal exudates, optic disc edema, and capillary non-perfusion [ Time Frame: 52 Weeks ]
    Percentage of patients with resolution of retinal hemorrhages, retinal exudates, optic disc edema, capillary non-perfusion
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravitreal Aflibercept Injection for Radiation Retinopathy Trial
Official Title  ICMJE Intravitreal Aflibercept Injection (IAI) for Radiation Retinopathy Trial (ARRT)
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.
Detailed Description

Approximately 30 eyes will be randomized (1:1 ratio) into either Group 1 or Group 2. Slit lamp exam and Indirect ophthalmoscopy will be performed at every study visit, where retinopathy level will be assessed. SD-OCT will be performed at each visit. Fluorescein angiogram will be performed at screen, week 26 and week 52. All other imaging studies will be standard of care at the discretion of the investigator.

This trial will compare the results of 2 groups, with different treatment intervals, to assess the safety of intravitreal Aflibercept injections (IAI) for the treatment of radiation retinopathy. Patients in each group will be followed for a total of 52 weeks.

Group 1: 15 Patients will receive a loading dose of 3 IAI. They will receive 2 mg IAI at screening/baseline, week 4, week 8, and week 12. A follow-up visit will occur at week 12. If the extension criteria are met, the patient will be extended by 2 weeks. The patient will continue to be followed per the treat and extend protocol described below.

Group 2: Patients will not receive a loading dose. They will receive 2 mg IAI at screening/baseline followed by a visit at week 4. At week 4, if the extension criteria are met, the patient will be extended by 2 weeks. The patient will continue to be followed per the treat and extend protocol described below.

Treat & Extend Protocol Patients can be extended as long as they meet the following criteria -

  • Absence of retinal fluid (resolution of intraretinal and subretinal fluid on SD-OCT; Small intraretinal cysts that do not distort foveal contour on SD-OCT are acceptable and can be considered "dry".) AND
  • Less than 5 ETDRS letter loss from previous visit due to new or persistent retinal edema.

IAI will be rendered at every visit (treatment at the week 26 mandatory visit will be administered based on the treat and extend status), no earlier than 4 days before the target date and no later than 4 days after the target date. 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, the 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.

All patients will have a mandatory study visit at Week 52 (final study visit). No study treatment will be administered after week 50 or at a study termination visit. If a patient receives treatment after week 48, they will return 4 weeks after the last clinic visit for the final study visit (instead of at week 52).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Radiation Retinopathy
Intervention  ICMJE Drug: Aflibercept
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.
Other Name: Eylea
Study Arms  ICMJE
  • Experimental: Loading Dose

    15 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.

    Intervention: Drug: Aflibercept
  • Experimental: Treat and Extend

    15 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.

    Intervention: Drug: Aflibercept
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 20, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2019
Estimated Primary Completion Date January 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

  1. Metastatic cancer or any active primary cancer, at time of enrollment
  2. Prior treatment with anti VEGF in the study within 60 days of screen in the study eye
  3. Prior intravitreal or subconjunctival treatment with cortical steroids within 90 days of screen in the study eye
  4. Macular ischemia (defined as greater than 5 disc areas), as assessed by the investigator
  5. Media opacity obscuring a view of the fundus or any other reason for vision loss other than radiation retinopathy.
  6. Evidence of infectious ocular infection, in the study eye, at time of screening
  7. Pregnant or breast-feeding women
  8. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chelsey Moore 713-394-7575 chelsey.moore@houstonretina.com
Contact: Cassie Cone, BA 713-394-7537 cassandra.cone@houstonretina.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03085784
Other Study ID Numbers  ICMJE ARRT
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amy C Schefler, MD, Greater Houston Retina Research
Study Sponsor  ICMJE Amy C Schefler, MD
Collaborators  ICMJE Regeneron Pharmaceuticals
Investigators  ICMJE
Principal Investigator: Amy C Schefler, MD Retina Consultants Houston
PRS Account Greater Houston Retina Research
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP