Back to resultsCLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA)
Primary Purpose
Geographic Atrophy
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
CLG561
LFG316
Sham injection
Sponsored by
About this trial
This is an interventional treatment trial for Geographic Atrophy focused on measuring Geographic atrophy (GA), Macular degeneration, Dry age-related macular degeneration (AMD), Intravitreal (IVT), Retinal diseases, Fundus auto fluorescence (FAF)
Eligibility Criteria
Inclusion Criteria:
- Sign written informed consent form;
- Geographic atrophy in both eyes;
- Other protocol-specified inclusion criteria may apply.
Exclusion Criteria:
- Pregnant or lactating women and women of child-bearing potential;
- Any medical condition (systemic or ophthalmic) that may preclude the safe administration of test article or safe participation in this study;
- Any contraindications or hypersensitivities to any component of the LFG316 or CLG561 solution;
- Any contraindications to IVT injections;
- Ocular surgery in either eye within 90 days of screening;
- Uncontrolled ocular hypertension or glaucoma in the study eye;
- Other protocol-specified exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Sham Comparator
Arm Label
CLG561
CLG561+LFG316
Sham Injection
Arm Description
CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections
CLG561 5mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
One sham injection every 28 days for total of 12 sham injections
Outcomes
Primary Outcome Measures
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug
A serious adverse event (SAE) was defined as any adverse experience that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All SAEs related to the study drug are reported. No statistical analysis was conducted.
Mean Change From Baseline in Intraocular Pressure (IOP)
IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry and reported in millimeters of mercury (mmHg). A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline is defined as the last measurement prior to first dose of treatment. A more negative change indicates a greater amount of improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Change in GA Lesion Size From Baseline to Day 337 as Measured by Fundus Autofluorescence (FAF)
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis.
Secondary Outcome Measures
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis.
Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis. Day 421 measurements were only summarized descriptively and did not include any statistical modeling.
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS
Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS
Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.
Average Change in BCVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
BCVA was assessed using ETDRS testing at 4 meters. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Average Change in LLVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS
LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS
BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment and is reported categorically. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Total CLG561 Serum Concentrations up to Day 421
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Total LFG316 Serum Concentration up to Day 421
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Percentage of Subjects With Anti-CLG561 Antibodies up to Day 421
Samples were collected and assessed for anti-CLG561 antibodies.
Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421
Samples were collected and assessed for anti-LFG316 antibodies.
Full Information
NCT ID
NCT02515942
First Posted
August 3, 2015
Last Updated
May 17, 2019
Sponsor
Alcon Research
Collaborators
Novartis Institutes for BioMedical Research
1. Study Identification
Unique Protocol Identification Number
NCT02515942
Brief Title
CLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA)
Official Title
A Randomized, Multi-Center, Single Masked, Sham Controlled, Proof-of-Concept Study of Intravitreal CLG561 as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
September 25, 2015 (Actual)
Primary Completion Date
August 14, 2017 (Actual)
Study Completion Date
December 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alcon Research
Collaborators
Novartis Institutes for BioMedical Research
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 purpose of this study is to evaluate the safety and efficacy of 12 (every 28 days) intravitreal (IVT) injections of CLG561 as a monotherapy and in combination with LFG316 as compared to sham in subjects with geographic atrophy.
Detailed Description
This study consists of an up-to 30-day screening period, an approximately 336-day treatment period, and a follow-up period consisting of two visits occurring 4 and 16 weeks after the last administered injection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Geographic Atrophy
Keywords
Geographic atrophy (GA), Macular degeneration, Dry age-related macular degeneration (AMD), Intravitreal (IVT), Retinal diseases, Fundus auto fluorescence (FAF)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
114 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CLG561
Arm Type
Experimental
Arm Description
CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections
Arm Title
CLG561+LFG316
Arm Type
Experimental
Arm Description
CLG561 5mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Arm Title
Sham Injection
Arm Type
Sham Comparator
Arm Description
One sham injection every 28 days for total of 12 sham injections
Intervention Type
Drug
Intervention Name(s)
CLG561
Intervention Type
Drug
Intervention Name(s)
LFG316
Intervention Type
Drug
Intervention Name(s)
Sham injection
Intervention Description
Empty syringe (without a needle) placed against the eye
Primary Outcome Measure Information:
Title
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug
Description
A serious adverse event (SAE) was defined as any adverse experience that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. All SAEs related to the study drug are reported. No statistical analysis was conducted.
Time Frame
Up to Day 421
Title
Mean Change From Baseline in Intraocular Pressure (IOP)
Description
IOP (fluid pressure inside the eye) was measured by Goldmann applanation tonometry and reported in millimeters of mercury (mmHg). A higher IOP can be a greater risk for developing glaucoma or glaucoma progression (leading to optic nerve damage). Baseline is defined as the last measurement prior to first dose of treatment. A more negative change indicates a greater amount of improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Time Frame
Baseline (Day 1), Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309
Title
Change in GA Lesion Size From Baseline to Day 337 as Measured by Fundus Autofluorescence (FAF)
Description
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 337
Secondary Outcome Measure Information:
Title
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF
Description
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 85, Day 169, Day 253
Title
Mean Change in GA Lesion Size From Baseline to Day 421 as Measured by FAF
Description
Geographic atrophy, also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina which can lead to a loss of visual function over time. Geographic atrophy (GA) lesion size was assessed by a Central Reading Center (CRC) using FAF. Baseline is defined as the last measurement prior to first dose of treatment. One eye (study eye) contributed to the analysis. Day 421 measurements were only summarized descriptively and did not include any statistical modeling.
Time Frame
Baseline (Day 1), Day 421
Title
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS)
Description
BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 30, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337
Title
Change in Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS
Description
Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 2, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337
Title
Change in LLVA Deficit From Baseline up to Day 337 as Measured by ETDRS
Description
Low Luminance Visual Acuity (VA) was assessed using ETDRS testing at 4 meters with a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 2, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337
Title
Average Change in BCVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
Description
BCVA was assessed using ETDRS testing at 4 meters. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Time Frame
Baseline (Day 1), Day 281, Day 309, Day 337
Title
Average Change in LLVA From Baseline to the Period Day 281 to Day 337 as Measured by ETDRS
Description
LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. BCVA change was defined as a change in letters read from the baseline assessment. A positive change value indicates improvement. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Time Frame
Baseline (Day 1), Day 281, Day 309, Day 337
Title
Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS
Description
LLVA was assessed at 4 meters using a neutral density filter to reduce chart luminance to 3 candelas/m2. A deficit in LLVA is defined as a loss in letters read from baseline. Baseline is defined as the last measurement prior to first dose of treatment. Day 281, Day 309, and Day 337 were averaged and compared to baseline. A negative change value indicates improvement (more letters read). One eye (study eye) contributed to the analysis.
Time Frame
Baseline (Day 1), Day 281, Day 309, Day 337
Title
Percentage of Subjects With Letter Change in BCVA From Baseline up to Day 337 as Measured by ETDRS
Description
BCVA was assessed using ETDRS testing at 4 meters. Baseline is defined as the last measurement prior to first dose of treatment. BCVA change was defined as a change in letters read from the baseline assessment and is reported categorically. One eye (study eye) contributed to the analysis. No statistical analysis was conducted.
Time Frame
Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 30, Day 57, Day 85, Day 113, Day 141, Day 169, Day 197, Day 225, Day 253, Day 281, Day 309, Day 337
Title
Total CLG561 Serum Concentrations up to Day 421
Description
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time Frame
Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 85, Day 169, Day 253, Day 309, Day 337, Day 421
Title
Total LFG316 Serum Concentration up to Day 421
Description
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method.
Time Frame
Baseline (Day 1), Day 337, Day 421
Title
Percentage of Subjects With Anti-CLG561 Antibodies up to Day 421
Description
Samples were collected and assessed for anti-CLG561 antibodies.
Time Frame
Baseline (Day 1), up to Day 421
Title
Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421
Description
Samples were collected and assessed for anti-LFG316 antibodies.
Time Frame
Baseline (Day 1), up to Day 421
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Sign written informed consent form;
Geographic atrophy in both eyes;
Other protocol-specified inclusion criteria may apply.
Exclusion Criteria:
Pregnant or lactating women and women of child-bearing potential;
Any medical condition (systemic or ophthalmic) that may preclude the safe administration of test article or safe participation in this study;
Any contraindications or hypersensitivities to any component of the LFG316 or CLG561 solution;
Any contraindications to IVT injections;
Ocular surgery in either eye within 90 days of screening;
Uncontrolled ocular hypertension or glaucoma in the study eye;
Other protocol-specified exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sr Clinical Manager, Pharma, GCRA
Organizational Affiliation
Alcon Research
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Learn more about this trial
CLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA)
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