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

Primary Purpose

Neovascular Age-related Macular Degeneration

Status

Unknown status

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Intravitreal Aflibercept Injection 2mg

About this trial

This is an interventional treatment trial for Neovascular Age-related Macular Degeneration focused on measuring age-related macular degeneration

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Tennessee Retina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Continued Q2 Week Treatment

Treat-And-Extend Treatment

Arm Description

Will receive intravitreal aflibercept (2.0mg) injections for an additional four consecutive 2 week intervals at weeks 18, 20, 22, and 24

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.

Outcomes

Primary Outcome Measures

Adverse Events

Frequency and severity of ocular and systemic adverse events

Secondary Outcome Measures

Retinal Thickness

Central Subfield Thickness on Optical Coherence Tomography

Subretinal Fluid Height

Max subretinal fluid height week on Optical Coherence Tomography

Pigment Epithelial Detachment Height

Max pigment epithelial detachment height on Optical Coherence Tomography

Proportion of Dry Maculas

Proportion of eyes with a dry macula (no subretinal fluid on Optical Coherence Tomography)

Best-Corrected Visual Acuity

Mean best-corrected visual acuity

Change in Best-Corrected Visual Acuity

Mean change in best-corrected visual acuity from baseline

Proportion gaining >5 letters of Best-Corrected Visual Acuity

Proportion of eyes gaining > 5 letters

Treatment Burden

Mean number of injections administered

Ability to Extend Treatment Interval

Proportion of eyes able to be extended during treat-and-extend dosing

Full Information

NCT ID

NCT03468296

First Posted

March 8, 2018

Last Updated

April 18, 2018

Sponsor

Tennessee Retina

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03468296

Brief Title

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

Acronym

TRISTAR

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Unknown status

Study Start Date

April 2018 (Anticipated)

Primary Completion Date

October 2018 (Anticipated)

Study Completion Date

July 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tennessee Retina

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neovascular Age-related Macular Degeneration

Keywords

age-related macular degeneration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Continued Q2 Week Treatment

Arm Type

Experimental

Arm Description

Will receive intravitreal aflibercept (2.0mg) injections for an additional four consecutive 2 week intervals at weeks 18, 20, 22, and 24

Arm Title

Treat-And-Extend Treatment

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Intravitreal Aflibercept Injection 2mg

Other Intervention Name(s)

Aflibercept; EYLEA®; VEGF Trap-Eye

Intervention Description

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.

Primary Outcome Measure Information:

Title

Adverse Events

Description

Frequency and severity of ocular and systemic adverse events

Time Frame

Through Week 14

Secondary Outcome Measure Information:

Title

Retinal Thickness

Description

Central Subfield Thickness on Optical Coherence Tomography

Time Frame

Weeks 14, 16, 24, 52

Title

Subretinal Fluid Height

Description

Max subretinal fluid height week on Optical Coherence Tomography

Time Frame

Weeks 14, 16, 24, 52

Title

Pigment Epithelial Detachment Height

Description

Max pigment epithelial detachment height on Optical Coherence Tomography

Time Frame

Weeks 14, 16, 24, 52

Title

Proportion of Dry Maculas

Description

Proportion of eyes with a dry macula (no subretinal fluid on Optical Coherence Tomography)

Time Frame

Weeks 14, 16, 24, 52

Title

Best-Corrected Visual Acuity

Description

Mean best-corrected visual acuity

Time Frame

Weeks 14, 24, and 52

Title

Change in Best-Corrected Visual Acuity

Description

Mean change in best-corrected visual acuity from baseline

Time Frame

Weeks 14, 24, and 52

Title

Proportion gaining >5 letters of Best-Corrected Visual Acuity

Description

Proportion of eyes gaining > 5 letters

Time Frame

Weeks 14, 24, and 52

Title

Treatment Burden

Description

Mean number of injections administered

Time Frame

Through Week 52

Title

Ability to Extend Treatment Interval

Description

Proportion of eyes able to be extended during treat-and-extend dosing

Time Frame

Through Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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 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.

Facility Information:

Facility Name

Tennessee Retina

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Contact: