Back to resultsStudy of Intravitreal REGN2176-3 in Participants With Neovascular ("Wet") Age-Related Macular Degeneration (AMD) (CAPELLA)
Primary Purpose
Neovascular Age-Related Macular Degeneration
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
REGN2176-3
Intravitreal Aflibercept Injection (IAI)
Sponsored by
About this trial
This is an interventional treatment trial for Neovascular Age-Related Macular Degeneration
Eligibility Criteria
Key Inclusion Criteria:
- Men or women ≥50 years of age
- Active subfoveal CNV secondary to AMD as evidenced by FA in the study eye, as determined by the reading center, including juxtafoveal lesions that affect the fovea
- BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye at the screening visit
- Provide signed informed consent
Key Exclusion Criteria:
- Any prior treatment with anti-VEGF treatment in the study eye
- Any prior treatment (ie, systemic or ocular treatment) with PDGF or PDGFR inhibitors
- Dense fibrotic scar or atrophy in the study eye involving the center of the fovea
- Presence of retinal pigment epithelial tears or rips involving the macula in the study eye
- Prior vitrectomy in the study eye
- Any history of macular hole of stage 2 and above in the study eye
- Any intraocular or periocular surgery within 3 months of day 1 in the study eye, except lid surgery
- History of corneal transplant in the study eye
- Evidence of diabetic retinopathy or diabetic macular edema in either eye
- Positive serum human chorionic gonadotropin/urine pregnancy test at the screening or baseline visit
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
REGN2176-3 (1 mg: 2 mg)
REGN2176-3 (3 mg: 2 mg)
Intravitreal Aflibercept Injection (IAI) 2 mg
REGN2176-3 (3 mg: 2 mg) to IAI 2 mg
IAI 2 mg to REGN2176-3 (3 mg:2 mg)
Arm Description
Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly with IAI 2 mg up to Week 28, then criteria based re-dosing from Week 28-52.
IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly with REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) up to Week 28, then criteria based re-dosing from Week 28-52.
Outcomes
Primary Outcome Measures
Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye at Week 12
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.
Secondary Outcome Measures
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 12, as Measured by Optical Coherence Tomography (OCT)
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Percentage of Participants With Complete Resolution of Intraretinal and Subretinal Fluid From Baseline at Week 12 Measured by Optical Coherence Tomography (OCT)
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation.
Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 Measured by Fluorescein Angiography (FA)
The anatomical state of the retinal vasculature of the study eye and the fellow eye was evaluated by funduscopic examination, fundus photography and FA to evaluate the total lesion area, CNV area, classic CNV area, and fluorescein leakage. CNV area values measured in square millimeters, each disc area was equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes.
Change From Baseline in Total Lesion Size at Week 12 Measured by Fluorescein Angiography (FA)
Total Lesion Size was assessed by Fluorescein Angiography.
Percentage of Participants Who Gained At Least 15 Letters in BCVA From Baseline at Week 12, Measured by 4-meter Early Treatment Diabetic Retinopathy Scale (ETDRS)
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. This outcome assessed the percentage of participants who gained 15 or more letters of visual acuity at Week 12 compared with baseline.
Percent Change From Baseline in Subretinal Hyperreflectivity Material (SHM) at Week 12 Measured by Optical Coherence Tomography (OCT)
SHM was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement.
Change From Baseline in Central Retinal/Lesion Thickness at Week 12 Measured by Optical Coherence Tomography (OCT)
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Full Information
NCT ID
NCT02418754
First Posted
April 13, 2015
Last Updated
October 1, 2020
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02418754
Brief Title
Study of Intravitreal REGN2176-3 in Participants With Neovascular ("Wet") Age-Related Macular Degeneration (AMD)
Acronym
CAPELLA
Official Title
A Phase 2, Double-Masked, Randomized, Controlled, Multiple-Dose, Regimen-Ranging Study of the Efficacy and Safety of Intravitreal REGN2176-3 in Patients With Neovascular Age-Related Macular Degeneration
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
No additional efficacy seen with REGN2176-3 over aflibercept alone
Study Start Date
May 5, 2015 (Actual)
Primary Completion Date
August 17, 2016 (Actual)
Study Completion Date
April 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the study was to explore the effect of REGN2176-3 on the Early Treatment Diabetic Retinopathy Scale (ETDRS) best-corrected visual acuity (BCVA) in participants with neovascular age-related macular degeneration (AMD), compared to intravitreal aflibercept injection (IAI) monotherapy.
The secondary objectives of the study were the following:
To explore the effect of 2 dose levels of IVT REGN2176-3 on anatomical changes of CNV in participants with nAMD compared to IAI monotherapy (at week 12)
To evaluate if short-term treatment with REGN2176-3 followed by IAI monotherapy offered the same or additional benefit compared to continuous treatment with REGN2176-3. Also to determine if there was benefit in initiating IAI treatment prior to REGN2176-3 compared to continuous treatment with IAI.
To assess the safety and tolerability of IVT REGN2176-3 in participants with nAMD
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neovascular Age-Related Macular Degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
505 (Actual)
8. Arms, Groups, and Interventions
Arm Title
REGN2176-3 (1 mg: 2 mg)
Arm Type
Experimental
Arm Description
Intravitreal injection of REGN2176-3 (REGN2176 1 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
Arm Title
REGN2176-3 (3 mg: 2 mg)
Arm Type
Experimental
Arm Description
Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
Arm Title
Intravitreal Aflibercept Injection (IAI) 2 mg
Arm Type
Experimental
Arm Description
IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly up to Week 28, then criteria based re-dosing from Week 28-52.
Arm Title
REGN2176-3 (3 mg: 2 mg) to IAI 2 mg
Arm Type
Experimental
Arm Description
Intravitreal injection of REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) every 4 weeks for 12 weeks. After Week 12, dosing was monthly with IAI 2 mg up to Week 28, then criteria based re-dosing from Week 28-52.
Arm Title
IAI 2 mg to REGN2176-3 (3 mg:2 mg)
Arm Type
Experimental
Arm Description
IAI every 4 weeks for 12 weeks. After Week 12, dosing was monthly with REGN2176-3 (REGN2176 3 mg and REGN3 2 mg) up to Week 28, then criteria based re-dosing from Week 28-52.
Intervention Type
Drug
Intervention Name(s)
REGN2176-3
Intervention Type
Drug
Intervention Name(s)
Intravitreal Aflibercept Injection (IAI)
Other Intervention Name(s)
Eylea®
Primary Outcome Measure Information:
Title
Change From Baseline in Best Corrected Visual Acuity (BCVA) of the Study Eye at Week 12
Description
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Change from baseline calculated by subtracting baseline value from observed post-baseline value at Week 12.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 12, as Measured by Optical Coherence Tomography (OCT)
Description
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Time Frame
Baseline, Week 12
Title
Percentage of Participants With Complete Resolution of Intraretinal and Subretinal Fluid From Baseline at Week 12 Measured by Optical Coherence Tomography (OCT)
Description
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation.
Time Frame
Week 12
Title
Change From Baseline in Choroidal Neovascularization (CNV) Area at Week 12 Measured by Fluorescein Angiography (FA)
Description
The anatomical state of the retinal vasculature of the study eye and the fellow eye was evaluated by funduscopic examination, fundus photography and FA to evaluate the total lesion area, CNV area, classic CNV area, and fluorescein leakage. CNV area values measured in square millimeters, each disc area was equivalent to 2.54 mm^2 on the retina; lower values represent better outcomes.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Total Lesion Size at Week 12 Measured by Fluorescein Angiography (FA)
Description
Total Lesion Size was assessed by Fluorescein Angiography.
Time Frame
Baseline, Week 12
Title
Percentage of Participants Who Gained At Least 15 Letters in BCVA From Baseline at Week 12, Measured by 4-meter Early Treatment Diabetic Retinopathy Scale (ETDRS)
Description
Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at 4 meters. BCVA score was measured using an eye chart and was reported as the number of letters read correctly at a testing distance of 4 meters using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. This outcome assessed the percentage of participants who gained 15 or more letters of visual acuity at Week 12 compared with baseline.
Time Frame
Week 12
Title
Percent Change From Baseline in Subretinal Hyperreflectivity Material (SHM) at Week 12 Measured by Optical Coherence Tomography (OCT)
Description
SHM was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Central Retinal/Lesion Thickness at Week 12 Measured by Optical Coherence Tomography (OCT)
Description
CST was assessed using spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. SD-OCT was performed in the study eye after pupil dilation. A negative change from baseline indicated improvement. Change from baseline calculated by subtracting baseline value from LOCF post-baseline value at Week 12.
Time Frame
Baseline, Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Men or women ≥50 years of age
Active subfoveal CNV secondary to AMD as evidenced by FA in the study eye, as determined by the reading center, including juxtafoveal lesions that affect the fovea
BCVA ETDRS letter score of 73 to 24 (20/40 to 20/320) in the study eye at the screening visit
Provide signed informed consent
Key Exclusion Criteria:
Any prior treatment with anti-VEGF treatment in the study eye
Any prior treatment (ie, systemic or ocular treatment) with PDGF or PDGFR inhibitors
Dense fibrotic scar or atrophy in the study eye involving the center of the fovea
Presence of retinal pigment epithelial tears or rips involving the macula in the study eye
Prior vitrectomy in the study eye
Any history of macular hole of stage 2 and above in the study eye
Any intraocular or periocular surgery within 3 months of day 1 in the study eye, except lid surgery
History of corneal transplant in the study eye
Evidence of diabetic retinopathy or diabetic macular edema in either eye
Positive serum human chorionic gonadotropin/urine pregnancy test at the screening or baseline visit
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
City
Phoenix
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Tucson
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Arcadia
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Beverly Hills
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Irvine
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Tampa
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Winter Haven
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Augusta
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Marietta
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Chicago
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Lexington
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Paducah
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Jackson
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Southfield
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Minneapolis
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Florissant
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Lincoln
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Omaha
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Las Vegas
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East Setauket
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Great Neck
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New York
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Orchard Park
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Rochester
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Asheville
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Charlotte
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Cincinnati
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Oklahoma City
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Portland
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Kingston
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Monroeville
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Philadelphia
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Florence
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Ladson
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West Columbia
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Rapid City
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Knoxville
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Memphis
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Nashville
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Abilene
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Austin
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Dallas
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Fort Worth
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Houston
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McAllen
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San Antonio
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The Woodlands
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Willow Park
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Salt Lake City
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Burlington
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Vermont
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Fairfax
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Virginia
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Bellevue
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Akita
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Japan
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Asahikawa
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Japan
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Chiyoda-ku
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Japan
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Fukushima
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Japan
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Kawasaki
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Japan
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Matsumoto
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Japan
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Nagasaki
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Japan
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Nagoya
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Japan
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Osaka
Country
Japan
12. IPD Sharing Statement
Learn more about this trial
Study of Intravitreal REGN2176-3 in Participants With Neovascular ("Wet") Age-Related Macular Degeneration (AMD)
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