CLG561 Proof-of-Concept Study as a Monotherapy and in Combination With LFG316 in Subjects With Geographic Atrophy (GA)

Phase 2

Completed

• Conditions: Geographic Atrophy
• Interventions: Drug: CLG561; Drug: Sham injection; Drug: LFG316

• Registration Number: NCT02515942
• Lead Sponsor: Alcon Research

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.

Study Timeline

• Study First Submitted: 2015-08-03
• Study First Submitted QC: 2015-08-03
• Study First Posted: 2015-08-05
• Study Start: 2015-09-25
• Primary Completion: 2017-08-14
• Study Completion: 2017-12-01
• Disposition First Submitted: 2017-12-04
• Disposition First Submitted QC: 2017-12-04
• Disposition First Posted: 2017-12-07
• Results First Submitted: 2018-11-12
• Results First Submitted QC: 2018-11-28
• Results First Posted: 2018-12-19
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-17
• Last Update Posted: 2019-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 114

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CLG561+LFG316	CLG561	CLG561 5mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
CLG561+LFG316	LFG316	CLG561 5mg + LFG316 5 mg, one IVT injection every 28 days for a total of 12 injections
Sham Injection	Sham injection	One sham injection every 28 days for total of 12 sham injections
CLG561	CLG561	CLG561 10 mg, one IVT injection every 28 days for a total of 12 injections

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Intraocular Pressure (IOP)	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	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)	Baseline (Day 1), Day 337	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.
Number of Subjects With a Serious Adverse Event That, in the Opinion of the Investigator, is Related to the Study Drug	Up to Day 421	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.

Secondary Outcome Measures

Name	Time	Method
Change in GA Lesion Size From Baseline to Day 85, 169, and 253 as Measured by FAF	Baseline (Day 1), Day 85, Day 169, Day 253	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	Baseline (Day 1), Day 421	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 Low Luminance Visual Acuity (LLVA) From Baseline up to Day 337 as Measured by ETDRS	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	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	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	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	Baseline (Day 1), Day 281, Day 309, Day 337	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	Baseline (Day 1), Day 281, Day 309, Day 337	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.
Change in Best Corrected Visual Acuity (BCVA) From Baseline by Visit up to Day 337 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS)	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	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.
Average LLVA Deficit (Letters) Change From Baseline at Day 281 to Day 337 as Measured by ETDRS	Baseline (Day 1), Day 281, Day 309, Day 337	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	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	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	Baseline (Day 1), Day 2, Day 8, Day 15, Day 29, Day 85, Day 169, Day 253, Day 309, Day 337, 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	Baseline (Day 1), Day 337, 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	Baseline (Day 1), up to Day 421	Samples were collected and assessed for anti-CLG561 antibodies.
Percentage of Subjects With Anti-LFG316 Antibodies up to Day 421	Baseline (Day 1), up to Day 421	Samples were collected and assessed for anti-LFG316 antibodies.