Back to resultsLHA510 Proof-of-Concept Study as a Maintenance Therapy for Patients With Wet Age-Related Macular Degeneration
Primary Purpose
Exudative Age-Related Macular Degeneration
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LHA510 ophthalmic suspension
LHA510 vehicle
Ranibizumab ophthalmic solution
Sponsored by
About this trial
This is an interventional treatment trial for Exudative Age-Related Macular Degeneration focused on measuring LHA510, PoC, Age-related macular degeneration
Eligibility Criteria
Inclusion Criteria:
- Sign written informed consent form;
- Wet AMD;
- IVT anti-VEGF therapy for at least 6 months and a maximum of 7 years since the 3rd loading dose;
- BCVA 50 letters (approximate Snellen equivalent 20/100) or better in the study eye;
- Demonstrate ability to administer eye drops (subject or care-giver);
- CNV recently demonstrated high need for frequent anti-VEGF therapy and a sustained functional and clear anatomical response to the therapy in the study eye;
- Other protocol-specified inclusion criteria may apply.
Exclusion Criteria:
- Any active ocular or periocular infection or intraocular inflammation;
- Current or history of macular or retinal disease (if visually significant) other than wet AMD in the study eye;
- Current clinically significant vitreous hemorrhage or history of rhegmatogenous retinal detachment affecting the macula in the study eye;
- History of hypersensitivity to any of the study drugs or clinically relevant sensitivity to fluorescein dye or povidone iodine;
- Women of child-bearing potential;
- History of a medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study or a safe administration of investigational product;
- Other protocol-specified exclusion criteria may apply.
Sites / Locations
- Contact Alcon Call Center for Trial Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
LHA510
Vehicle
Arm Description
LHA510 ophthalmic suspension administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy.
LHA510 vehicle administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy.
Outcomes
Primary Outcome Measures
Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84
For subjects who completed the Day 84 visit, retreatment need status was positive if LUCENTIS® retreatment (injection) was required before or at Day 84, including requiring retreatment at or before the Day 84 visit with the actual retreatment performed at a later visit.
Secondary Outcome Measures
Time to First LUCENTIS® Retreatment Need Identification up to Day 84
The time was determined based on the visit of the treatment period when a patient was identified as requiring retreatment with LUCENTIS.
Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84
The number of LUCENTIS retreatment needs identified before or at the Day 84 visit (even if retreatment was applied at a later visit) for each patient was used in the analysis
Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56
The number of LUCENTIS® retreatment needs identified before or at the Day 28 and Day 56 visits (even if retreatment was applied at a later visit) for each subject was used in the analysis.
Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site
The thickness of the retina was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site
Measurement of best corrected (with spectacles or other visual corrective devices) visual acuity was conducted in each eye individually using ETDRS charts and reported in number of letters read correctly. An increase (gain) in letters read from the baseline assessment indicates improvement. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit
The thickness of the neuro-retina, at the level of the central subfield, was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Lesion Thickness by Visit
The thickness of the neovascular lesion was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of the neovascular lesion may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit
The thickness of subretinal fluid involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of subretinal fluid involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit
The thickness of pigment epithelial detachment involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of pigment epithelial detachment involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in Total Lesion Size by Visit
The total wet AMD lesion size was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in wet AMD lesion size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Change From Randomization Visit (Day -1) in CNV Size by Visit
The size of CNV (area of new blood vessels in the choroid layer of the retina) was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in CNV size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Plasma Concentration of LHA510 and CRA398
Samples collected from subjects, after multiple topical ocular dosing of LHA510, were analyzed to determine concentrations of LHA510 and its metabolite, CRA398. Plasma LHA510 and CRA398 concentrations were quantitated by a validated liquid chromatography-tandem mass spectroscopy assay method. Below the limit of quantification (BLQ) is treated as zero.
Full Information
NCT ID
NCT02355028
First Posted
January 28, 2015
Last Updated
May 31, 2018
Sponsor
Alcon, a Novartis Company
1. Study Identification
Unique Protocol Identification Number
NCT02355028
Brief Title
LHA510 Proof-of-Concept Study as a Maintenance Therapy for Patients With Wet Age-Related Macular Degeneration
Official Title
A Randomized, Double-Masked, Vehicle-Controlled Proof-Of-Concept Study for Topically Delivered LHA510 as a Maintenance Therapy in Patients With Wet Age-Related Macular Degeneration (AMD)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
March 3, 2015 (Actual)
Primary Completion Date
September 15, 2016 (Actual)
Study Completion Date
October 18, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alcon, a Novartis Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of 84 successive days of topically administered LHA510 compared to vehicle in reducing the number of patients requiring intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) therapy (Lucentis®) for recurrence of active choroidal neovascularization (CNV).
Detailed Description
On Day -1, patients will receive an IVT Lucentis® injection in the study eye, and then will be randomized to receive either topical LHA510 ophthalmic suspension or vehicle in a 1:1 ratio for 84 days. Patients with recurrence of active CNV in the study eye during the study will receive rescue IVT Lucentis® injections. Following the treatment period, subjects will return for a follow-up visit and a disposition visit. Only one eye (designated as the study eye) will be dosed with either topical LHA510 or vehicle per patient.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Exudative Age-Related Macular Degeneration
Keywords
LHA510, PoC, Age-related macular degeneration
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LHA510
Arm Type
Experimental
Arm Description
LHA510 ophthalmic suspension administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy.
Arm Title
Vehicle
Arm Type
Placebo Comparator
Arm Description
LHA510 vehicle administered topically in the study eye as specified in the protocol for 84 days, with ranibizumab ophthalmic solution for IVT injection as standard of care rescue therapy.
Intervention Type
Drug
Intervention Name(s)
LHA510 ophthalmic suspension
Intervention Type
Drug
Intervention Name(s)
LHA510 vehicle
Intervention Description
Inactive ingredients used as a placebo comparator
Intervention Type
Drug
Intervention Name(s)
Ranibizumab ophthalmic solution
Other Intervention Name(s)
Lucentis®
Intervention Description
For intravitreal (IVT) injection
Primary Outcome Measure Information:
Title
Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84
Description
For subjects who completed the Day 84 visit, retreatment need status was positive if LUCENTIS® retreatment (injection) was required before or at Day 84, including requiring retreatment at or before the Day 84 visit with the actual retreatment performed at a later visit.
Time Frame
Day 84
Secondary Outcome Measure Information:
Title
Time to First LUCENTIS® Retreatment Need Identification up to Day 84
Description
The time was determined based on the visit of the treatment period when a patient was identified as requiring retreatment with LUCENTIS.
Time Frame
Day 14, Day 28, Day 56, Day 84
Title
Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84
Description
The number of LUCENTIS retreatment needs identified before or at the Day 84 visit (even if retreatment was applied at a later visit) for each patient was used in the analysis
Time Frame
Up to Day 84
Title
Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56
Description
The number of LUCENTIS® retreatment needs identified before or at the Day 28 and Day 56 visits (even if retreatment was applied at a later visit) for each subject was used in the analysis.
Time Frame
Day 28, Day 56
Title
Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site
Description
The thickness of the retina was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 14, Day 28, Day 56, Day 84
Title
Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site
Description
Measurement of best corrected (with spectacles or other visual corrective devices) visual acuity was conducted in each eye individually using ETDRS charts and reported in number of letters read correctly. An increase (gain) in letters read from the baseline assessment indicates improvement. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 14, Day 28, Day 56, Day 84
Title
Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit
Description
The thickness of the neuro-retina, at the level of the central subfield, was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 28, Day 84
Title
Change From Randomization Visit (Day -1) in Lesion Thickness by Visit
Description
The thickness of the neovascular lesion was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of the neovascular lesion may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 28, Day 84
Title
Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit
Description
The thickness of subretinal fluid involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of subretinal fluid involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 28, Day 84
Title
Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit
Description
The thickness of pigment epithelial detachment involving the fovea was measured using SD-OCT and reported as a difference, in micrometers, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness of pigment epithelial detachment involving the fovea may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 28, Day 84
Title
Change From Randomization Visit (Day -1) in Total Lesion Size by Visit
Description
The total wet AMD lesion size was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in wet AMD lesion size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 84
Title
Change From Randomization Visit (Day -1) in CNV Size by Visit
Description
The size of CNV (area of new blood vessels in the choroid layer of the retina) was measured using FA and reported as a difference, in millimeter squared, between a given post-Randomization Visit and Randomization Visit (Day-1). A negative number indicates a reduction, whereas a positive number indicates an increase. An increase in CNV size may indicate a progression of the underlying disease. Only one eye (study eye) contributed to the analysis.
Time Frame
Day -1, Day 84
Title
Plasma Concentration of LHA510 and CRA398
Description
Samples collected from subjects, after multiple topical ocular dosing of LHA510, were analyzed to determine concentrations of LHA510 and its metabolite, CRA398. Plasma LHA510 and CRA398 concentrations were quantitated by a validated liquid chromatography-tandem mass spectroscopy assay method. Below the limit of quantification (BLQ) is treated as zero.
Time Frame
Day 28, Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Sign written informed consent form;
Wet AMD;
IVT anti-VEGF therapy for at least 6 months and a maximum of 7 years since the 3rd loading dose;
BCVA 50 letters (approximate Snellen equivalent 20/100) or better in the study eye;
Demonstrate ability to administer eye drops (subject or care-giver);
CNV recently demonstrated high need for frequent anti-VEGF therapy and a sustained functional and clear anatomical response to the therapy in the study eye;
Other protocol-specified inclusion criteria may apply.
Exclusion Criteria:
Any active ocular or periocular infection or intraocular inflammation;
Current or history of macular or retinal disease (if visually significant) other than wet AMD in the study eye;
Current clinically significant vitreous hemorrhage or history of rhegmatogenous retinal detachment affecting the macula in the study eye;
History of hypersensitivity to any of the study drugs or clinically relevant sensitivity to fluorescein dye or povidone iodine;
Women of child-bearing potential;
History of a medical condition that, in the opinion of the Investigator, would preclude scheduled study visits, completion of the study or a safe administration of investigational product;
Other protocol-specified exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Scientist, CA CSI, ID/Multi-TA
Organizational Affiliation
Novartis Institutes for BioMedical Research, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Contact Alcon Call Center for Trial Locations
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76134
Country
United States
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
LHA510 Proof-of-Concept Study as a Maintenance Therapy for Patients With Wet Age-Related Macular Degeneration
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