A Study to Evaluate the Safety and Clinical Response of Subretinal Administration of CNTO 2476 in Participants With Geographic Atrophy

Phase 2

Completed

• Conditions: Visual Acuity; Geographic Atrophy; Macular Degeneration
• Interventions: Drug: CNTO 2476 3.0 x 10^5 cells; Device: Subretinal Delivery System

• Registration Number: NCT02659098
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to evaluate the safety and performance profile of the suprachoroidal surgical approach and the Delivery System.

Detailed Description

This is a multicenter (when more than one hospital or medical school team work on a medical research study) study which includes an initial unmasked safety phase. The duration of participation in the study for each participant is approximately 3 years. Efficacy will be evaluated at 6 months, 12 months and annually thereafter. Participants' safety will be monitored throughout the study.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2015-12-04
• Study First Submitted: 2015-12-07
• Study First Submitted QC: 2016-01-14
• Study First Posted: 2016-01-20
• Primary Completion: 2019-06-05
• Study Completion: 2019-06-05
• Status Verified: 2020-06
• Results First Submitted: 2020-06-02
• Results First Submitted QC: 2020-06-02
• Last Update Submitted: 2020-06-02
• Results First Posted: 2020-06-23
• Last Update Posted: 2020-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Diagnosis of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) confirmed within 45 days prior to initial randomization verified by the central reading center
• Study eyes will have a best corrected visual acuity (BCVA) of 20/80 to 20/800 [Early Treatment Diabetic Retinopathy Study (ETDRS) log of the minimum angle of resolution (logMAR) value 0.6-1.6]. The treatment eye will be that with the worse BCVA at Screening. If BCVA is clinically equivalent, the eye with the larger GA determines the study eye
• Participant is a suitable candidate for ophthalmologic surgery, is willing and able to comply with the surgical procedure, scheduled visits, treatment plan, laboratory tests and other study procedures. Participant has met criteria of the surgery center anti-coagulation protocol, if applicable
• Each participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study

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Exclusion Criteria

• Participant has a history of neovascular ("wet") AMD in the treatment eye, including evidence of retinal pigment epithelium rips or evidence of subretinal or choroidal neovascularization or fluid. In cases where imaging is inconclusive, review of the case with the study site, considering history and imaging will determine eligibility. History or evidence of neovascular AMD in the fellow eye is allowed, if anti-vascular endothelial growth factor (VEGF) therapy has not been required for at least 8 weeks prior to Screening
• Geographic atrophy secondary to any causes other than AMD in either eye
• A diagnosis of glaucoma with an intraocular pressure (IOP) greater than or equal to (>=) 25 millimeter of mercury (mmHg) while being treated with an ocular hypotensive drug. Treatment should be no more than 1 drug preparation/combination, which can contain 1 or 2 ocular hypotensive active ingredients; participants receiving more than 2 ocular hypotensive active ingredients are excluded
• Nuclear sclerotic cataract, cortical spoking, posterior subcapsular cataract above Grade 2 per Age Related Eye Disease Study (AREDS) scale or any other ophthalmologic condition that reduces the clarity of the media that, in the opinion of the investigator or reading center, interferes with ophthalmologic examination (example, corneal abnormalities, inadequate pupillary dilation), surgery or imaging in the study eye
• Myopia greater than minus (>-) 8 diopters and participants with greater than (>) 4 diopters of astigmatism, and greater than plus (>+) 10 diopters of hyperopia

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-Label Safety Run-in Phase: Treatment Group	CNTO 2476 3.0 x 10^5 cells	Participants will receive CNTO 2476 3.0 x 10\^5 cells in 50 microliter (mcL). CNTO 2476 will be delivered using the custom-designed Delivery System.
Open-Label Safety Run-in Phase: Treatment Group	Subretinal Delivery System	Participants will receive CNTO 2476 3.0 x 10\^5 cells in 50 microliter (mcL). CNTO 2476 will be delivered using the custom-designed Delivery System.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Best Corrected Visual Acuity (BCVA) Total Letters Score at Month 1- Treated Eye	Baseline and Month 1	Best corrected visual acuity (BCVA) was assessed in the study eye (Treated eye). BCVA measurements were made using the logarithm of the minimum angle of resolution (logMAR) visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 3- Treated Eye	Baseline and Month 3	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Total Letters Score at Month 24- Treated Eye	Baseline and Month 24	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Total Letters Score at Month 36- Treated Eye	Baseline and Month 36	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 24- Fellow Eye	Baseline and Month 24	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 30- Fellow Eye	Baseline and Month 30	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 36- Fellow Eye	Baseline and Month 36	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 12- Treated Eye	Baseline and Month 12	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 18- Treated Eye	Baseline and Month 18	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Total Letters Score at Month 1- Fellow Eye	Baseline and Month 1	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 2- Fellow Eye	Baseline and Month 2	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 3- Fellow Eye	Baseline and Month 3	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 6- Fellow Eye	Baseline and Month 6	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 6- Treated Eye	Baseline and Month 6	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity (BCVA) Total Letters Score at Month 30- Treated Eye	Baseline and Month 30	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 12- Fellow Eye	Baseline and Month 12	BCVA was assessed in the fellow eye. BCVA measurements were made using logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there are 5 letters per line, the total score for a line on the logMAR chart represents a change of 0.1 log units. The formula for calculating the logMAR BCVA score is: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 18- Fellow Eye	Baseline and Month 18	BCVA was assessed in the fellow eye. BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.
Change From Baseline in Best Corrected Visual Acuity Total Letters Score at Month 2- Treated Eye	Baseline and Month 2	BCVA was assessed in the study eye (Treated eye). BCVA measurements were made using the logMAR visual acuity testing charts. Each letter on the chart has a score value of 0.02 log units. Since there were 5 letters per line, the total score for a line on the logMAR chart represented a change of 0.1 log units. The formula for calculating the logMAR BCVA score was: 1.7 - 0.02\*number of letters read. A lower BCVA score indicates better vision. A negative change score indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Up to Months 36	Number of participants with TEAEs and SAEs were assessed. An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment and can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. SAE is defined as any untoward medical occurrence that at any dose results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect, Is a suspected transmission of any infectious agent via a medicinal product.
Number of Participants With Ocular Treatment-emergent Adverse Events	Up to Months 36	Number of participants with ocular TEAE were assessed. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the treatment and can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product.
Percentage of Participants Losing Greater Than or Equal to (>=) 15 Best Corrected Visual Acuity Letters: Treated Eye	Months 1, 2 , 3, 6, 12, 18, 24, 30 and 36	BCVA was assessed as letters read using early treatment diabetic retinopathy study charts and reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye (Treated eye). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. The percentage of participants losing \>=15 BCVA in the study eye were reported.
Percentage of Participants Losing >=15 Best Corrected Visual Acuity Letters: Fellow Eye	Months 1, 2 , 3, 6, 12, 18, 24, 30 and 36	BCVA was assessed as letters read using early treatment diabetic retinopathy study charts and reported as the number of letters read correctly (ranging from 0 to 100 letters) in the fellow eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. The percentage of participants losing \>=15 BCVA in the fellow eye were reported.
Change From Baseline in Best Corrected Visual Acuity Letters at Months 6 and 12: Treated Eye	Baseline, Months 6 and 12	BCVA was assessed as letters read using early treatment diabetic retinopathy study charts and reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye (Treated eye). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Change From Baseline in Best Corrected Visual Acuity at Months 6 and 12: Fellow Eye	Baseline, Months 6 and 12	BCVA was assessed as letters read using early treatment diabetic retinopathy study charts and reported as the number of letters read correctly (ranging from 0 to 100 letters) in the fellow eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Change From Baseline in Growth Rate of Geographic Atrophy (GA) Lesion Area at Months 6 and 12: Treated Eye	Baseline, Months 6 and 12	The area of GA was determined based primarily on fundus autofluorescence (FAF). The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).
Change From Baseline in Growth Rate of Geographic Atrophy Lesion Area at Months 6 and 12: Fellow Eye	Baseline, Months 6 and 12	The area of GA was determined based primarily on FAF. The change in GA lesion area was measured by FAF and analysis of FAF images was performed by the central reading center. A positive change from baseline indicates an increase in size of GA lesion area (worsening; disease progression).