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

NCT ID: NCT03468296

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-30
• Study Completion Date: 2019-07-31

Brief Summary

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.

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.

Conditions

Neovascular Age-related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Intravitreal Aflibercept Injection 2mg

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Intravitreal Aflibercept Injection 2mg

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Aflibercept; EYLEA®; VEGF Trap-Eye

Eligibility Criteria

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

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)

• 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.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Tennessee Retina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tennessee Retina

Nashville, Tennessee, United States

Countries

United States

Facility Contacts

Eric Schneider, MD

Role: primary

eschneider@tnretina.com

615-983-6000

References

Schneider EW, Thomas MK, Recchia FM, Reichstein DA, Awh CC. SUSTAINED BIWEEKLY AFLIBERCEPT FOR REFRACTORY NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The Prospective TRISTAR Study. Retina. 2023 May 1;43(5):739-746. doi: 10.1097/IAE.0000000000003729.

Reference Type: DERIVED

PMID: 36728874 (View on PubMed)

Other Identifiers

VGFTe-AMD-1819

Identifier Type: -

Identifier Source: org_study_id