Two-week Retreatment Interval Study for Treated Age-related Macular Degeneration Refractory to Monthly Aflibercept (TRISTAR)

This study is designed to evaluate the safety and efficacy of every 2 week intravitreal aflibercept injections in a population of neovascular AMD patients that have demonstrated refractory subretinal fluid with or without intraretinal fluid despite prior monthly intravitreal aflibercept treatment.

Study Overview

• Status: Unknown
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Intravitreal Aflibercept Injection 2mg

Detailed Description

Eligible patients will be scheduled to receive intravitreal aflibercept (2.0mg) injections for six consecutive 2 week (13-15 days) intervals with injections administered at weeks 0, 2, 4, 6, 8, 10, and 12. The primary endpoint visit to assess response to sustained q2week therapy will be at the week 14 visit. No treatment will be administered at this visit. All patients will then return at week 16 for the randomization visit and receive a repeat intravitreal aflibercept (2.0mg) injection. For purposes of randomization, patients will be separated into the following groups:

• Q2 week complete responders: absence of subretinal fluid on OCT at week 16
• Q2 week incomplete responders: persistent subretinal fluid on OCT at week 16

The "q2 week complete responders" will subsequently be transitioned to a treat and extend regimen with a minimum inter-treatment interval of 4 weeks through week 24. The "q2 week incomplete responders" will be randomized in a 1:1 fashion into one of two arms:

• Continued q2 week treatment: intravitreal aflibercept (2.0mg) injections for an additional four consecutive 2 week intervals at weeks 18, 20, 22, and 24
• Transition to treat-and-extend treatment: through week 24 with a minimum inter-treatment interval of q4 weeks. This arm is identical to regimen for "q2 week complete responders."

Beginning in week 24, all patients (all groups) will undergo treatment delivered on a treat-and-extend basis with a minimum inter-treatment interval of 4 weeks through the week 50. Patient visits will be treated no more frequent than q4 weeks during treat-and-extend portions of the protocol.

All patients will have a mandatory study termination visit at week 52 (-1/+2 weeks). No study treatment will be administered after week 50. Patients receiving a study treatment after week 48 will return 4 weeks after this final study treatment for study termination visit. Patients receiving a study treatment at or before week 48 in whom the treat-and-extend protocol would dictate a subsequent visit after week 52 will instead return at week 52 for a study termination visit.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 50 years
• A diagnosis of choroidal neovascularization related to age-related macular degeneration
• ETDRS refracted BCVA ≥ 20/200
• Prior treatment with any anti-VEGF agent for ≥ 12 months
• Prior treatment with at least five intravitreal aflibercept at the time of screening (week -2) with an average inter-treatment interval <35 days
• Presence of persistent subretinal fluid with or without intraretinal fluid on OCT at most recent standard of care visit occurring 28-35 days following most recent intravitreal aflibercept injection

• Demonstration of definite improvement in overall retinal thickness and/or subretinal fluid on OCT based on evaluation of examining investigator at screening visit (week -2) 13-15 days following most recent standard of care visit

  o Note: screening OCT will be performed prior to dilation to allow for undilated ETDRS BCVA testing following confirmation of eligibility

• Willing and able to comply with clinic visits and study-related procedures
• Provide signed informed consent

Ocular Exclusion Criteria:

• Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy in the study eye
• Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye
• Concurrent eye disease in the study eye that could compromise visual acuity (e.g. advanced diabetic retinopathy, advanced glaucoma)
• Active intraocular inflammation (grade trace or above) in the study eye
• Current vitreous hemorrhage in the study eye
• History of macula-involving rhegmatogenous retinal detachment or macular hole (Stage 2 - 4) in the study eye
• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
• Aphakia in the study eye
• Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥30 mmHg despite treatment with anti-glaucoma medication)

Systemic Exclusion Criteria

• Use of systemic anti-VEGF medications within 6 months of screening visit
• History of cerebrovascular accident, myocardial infarction, ventricular arrhythmia, unstable angina, coronary or peripheral artery bypass or stenting within 6 months of day 0
• History of deep vein thrombosis or pulmonary embolus within 6 months of day 0
• Uncontrolled hypertension (>160/100 on medical treatment)
• Pregnant or breast-feeding women

• Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception prior to the initial dose administration (baseline visit, week 0). 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 child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Continued Q2 Week Treatment; Will receive intravitreal aflibercept (2.0mg) injections for an additional four consecutive 2 week intervals at weeks 18, 20, 22, and 24	Drug: Intravitreal Aflibercept Injection 2mg; Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration.; Other Names: Aflibercept; EYLEA®; VEGF Trap-Eye
ACTIVE_COMPARATOR: Treat-And-Extend Treatment; Will receive intravitreal aflibercept (2.0mg) injections on a treat-and-extend basis through week 24 with a minimum inter-treatment interval of q4 weeks.	Drug: Intravitreal Aflibercept Injection 2mg; Aflibercept is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration.; Other Names: Aflibercept; EYLEA®; VEGF Trap-Eye

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Frequency and severity of ocular and systemic adverse events	Through Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retinal Thickness	Central Subfield Thickness on Optical Coherence Tomography	Weeks 14, 16, 24, 52
Subretinal Fluid Height	Max subretinal fluid height week on Optical Coherence Tomography	Weeks 14, 16, 24, 52
Pigment Epithelial Detachment Height	Max pigment epithelial detachment height on Optical Coherence Tomography	Weeks 14, 16, 24, 52
Proportion of Dry Maculas	Proportion of eyes with a dry macula (no subretinal fluid on Optical Coherence Tomography)	Weeks 14, 16, 24, 52
Best-Corrected Visual Acuity	Mean best-corrected visual acuity	Weeks 14, 24, and 52
Change in Best-Corrected Visual Acuity	Mean change in best-corrected visual acuity from baseline	Weeks 14, 24, and 52
Proportion gaining >5 letters of Best-Corrected Visual Acuity	Proportion of eyes gaining > 5 letters	Weeks 14, 24, and 52
Treatment Burden	Mean number of injections administered	Through Week 52
Ability to Extend Treatment Interval	Proportion of eyes able to be extended during treat-and-extend dosing	Through Week 52

Collaborators and Investigators

• Sponsor: Tennessee Retina
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2018
• Primary Completion (ANTICIPATED): October 1, 2018
• Study Completion (ANTICIPATED): July 1, 2019

Study Registration Dates

• First Submitted: March 8, 2018
• First Submitted That Met QC Criteria: March 14, 2018
• First Posted (ACTUAL): March 16, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2018
• Last Update Submitted That Met QC Criteria: April 18, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: age-related macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: VGFTe-AMD-1819

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No