Clinical trial NCT01617148: Wet Macular Degeneration Study to Compare Ranibizumab or Bevacizumab to Aflibercept
Official title: A Single Arm, Investigator Initiated Study of the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Injection in Subjects With Exudative Age-related Macular Degeneration Previously Treated With Ranibizumab or Bevacizumab (ASSESS Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Exudative Macular Degeneration
Keywords: Exudative Macular Degeneration
Aflibercept
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2012-06-12
Enrollment: 26
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will examine the use of Aflibercept in patients with exudative macular degeneration requiring intravitreal injections. Patients will be followed for 24 months. The follow up phase will be completed at month 36.

Detailed description: The purpose of this study is to examine the use of Aflibercept in patients who have been previously treated with Ranibizumab or Bevacizumab for exudative macular degeneration. Specifically, we will examine its effect on macular degeneration, measured by SDOCT (Spectral Domain Optical Coherence Tomography) and ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity. This will be a prospective study with patients to receive an intravitreal injection of Aflibercept at the time of treatment.

Eligibility criteria: Inclusion Criteria

A subject must meet the following criteria to be eligible for inclusion in the study:

1. Signed Informed Consent.
2. Men and women ≥ 50 years of age.
3. Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by historical optical coherence tomographies (OCTs) and angiograms in the study eye.
4. CNV must be at least 50% of total lesion size by either previous or current angiogram.
5. ETDRS best-corrected visual acuity of: 20/25 to 20/320 (letter score of 73 to 25) in the study eye.
6. Willing, committed, and able to return for all clinic visits and complete all study related procedures.
7. At least one injection of Ranibizumab or Bevacizumab within 3 months of enrollment for active exudative AMD.
8. Active need for anti- vascular endothelial growth factor (anti-VEGF) therapy at study entry based on the following criteria:

   1. Presence of fluid by either optical coherence tomography (OCT) or clinical examination (further defined as intraretinal, cystoid, subretinal, worsening pigment epithelial detachment)
   2. Presence of new hemorrhage on clinical examination

Exclusion Criteria

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

1. Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye, except dietary supplements or vitamins.
2. Prior systemic anti-VEGF therapy, investigational or FDA/Health Canada approved, is only allowed up to 3 months prior to first dose, and will not be allowed during the study.
3. Presence of retinal pigment epithelial tears or rips involving the macula in the study
4. History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye.
5. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye.
6. History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
7. Prior vitrectomy in the study eye.
8. History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
9. Any history of macular hole of stage 2 and above in the study eye.
10. Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection.
11. Prior trabeculectomy or other filtration surgery in the study eye.
12. Uncontrolled glaucoma at baseline evaluation (defined as intraocular pressure ≥25 mmHg despite treatment with anti-glaucoma medication) in the study eye.
13. Active intraocular inflammation in either eye.
14. Active ocular or periocular infection in either eye.
15. Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
16. Any history of uveitis in either eye.
17. Active scleritis or episcleritis in either eye.
18. Presence or history of scleromalacia in either eye.
19. Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye.
20. Previous therapeutic radiation in the region of the study eye.
21. History of corneal transplant or corneal dystrophy in the study eye.
22. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of safety, or fundus photography.
23. Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 52 week study period.
24. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
25. Participation as a subject in any clinical study within the 12 weeks prior to Day 1.
26. Any systemic with an investigational agent in the past 3 months prior to Day 1.
27. The use of long acting intraocular steroids or photodynamic therapy in the 6 months prior to day 1.
28. Any history of allergy to povidone iodine.
29. Pregnant or breast-feeding women
30. Women of childbearing potential\* who are unwilling to practice adequate contraception during the study (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 (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly)

    * \*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.

Primary outcomes:
measure: Change in Central Subfield Thickness From Baseline at 12 Months
timeFrame: baseline and 12 months
Secondary outcomes:
measure: Change in Best-corrected Visual Acuity From Baseline at 12 Months
timeFrame: Baseline and 12 months
measure: Change in Macular Volume From Baseline at 12 Months.
timeFrame: baseline and 12 months
measure: Change in Cube Average Thickness From Baseline at 12 Months
timeFrame: baseline and 12 months
measure: Percentage of Patients Who Gained Greater Than 15 Letters of Vision From Baseline at 12 Months.
timeFrame: baseline and 12 months
measure: Percentage of Patients Who Lost Greater Than 15 Letters of Vision From Baseline at 12 Months
timeFrame: baseline and 12 months
measure: Percentage of Subjects Who Were 20/40 or Better at Month 12.
timeFrame: month 12
measure: Percentage of Subjects Who Were 20/200 or Worse at Month 12.
timeFrame: month 12
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cole Eye Institute, Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Rishi P Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Singh RP, Srivastava SK, Ehlers JP, Silva FQ, Bedi R, Schachat AP, Kaiser PK. A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study): 12-month analysis. Clin Ophthalmol. 2015 Sep 22;9:1759-66. doi: 10.2147/OPTH.S87043. eCollection 2015.
citation: Singh RP, Srivastava S, Ehlers JP, Bedi R, Schachat AP, Kaiser PK. A single-arm, investigator-initiated study of the efficacy, safety and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration, previously treated with ranibizumab or bevacizumab: 6-month interim analysis. Br J Ophthalmol. 2014 Jun;98 Suppl 1(Suppl 1):i22-27. doi: 10.1136/bjophthalmol-2013-304798.