LHA510 Proof-of-Concept Study as a Maintenance Therapy for Patients With Wet Age-Related Macular Degeneration

• ClinicalTrials.gov Identifier: NCT02355028
• Recruitment Status: Completed
• First Posted: February 4, 2015
• Results First Posted: November 14, 2017
• Last Update Posted: July 2, 2018
• Sponsor: Alcon, a Novartis Company
• Information provided by (Responsible Party): Alcon Research ( Alcon, a Novartis Company )

Tracking Information

• First Submitted Date: January 28, 2015
• First Posted Date: February 4, 2015
• Results First Submitted Date: October 11, 2017
• Results First Posted Date: November 14, 2017
• Last Update Posted Date: July 2, 2018
• Actual Study Start Date: March 3, 2015
• Actual Primary Completion Date: September 15, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 13, 2017)

Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: February 2, 2015): Number of patients requiring Lucentis® retreatment before or at Day 84 [ Time Frame: Day 84 ]

Current Secondary Outcome Measures (submitted: November 13, 2017)

• Time to First LUCENTIS® Retreatment Need Identification up to Day 84 [ Time Frame: Day 14, Day 28, Day 56, 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 [ Time Frame: 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 [ Time Frame: Day 28, Day 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 [ Time Frame: Day -1, Day 14, Day 28, Day 56, Day 84 ]
  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 [ Time Frame: Day -1, Day 14, Day 28, Day 56, Day 84 ]
  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 [ Time Frame: Day -1, Day 28, Day 84 ]
  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 [ Time Frame: Day -1, Day 28, Day 84 ]
  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 [ Time Frame: Day -1, Day 28, Day 84 ]
  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 [ Time Frame: Day -1, Day 28, Day 84 ]
  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 [ Time Frame: Day -1, Day 84 ]
  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 [ Time Frame: Day -1, Day 84 ]
  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 [ Time Frame: Day 28, Day 84 ]
  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.

Original Secondary Outcome Measures (submitted: February 2, 2015)

• Time to first injection of Lucentis® required up to Day 84 [ Time Frame: Up to Day 84 ]
• Number of Lucentis® injections required up to Day 84 [ Time Frame: Day 84 ]
• Change from Eligibility (Day -1) in central subfield thickness total (CSFTtot) at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in Best Corrected Visual Acuity (BCVA) at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in central retinal lesion thickness (CRLT) at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in lesion thickness at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in subretinal fluid - foveal involvement (SRFfi) thickness at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in pigment epithelial detachment - foveal involvement (PEDfi) thickness at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in total lesion size at each visit [ Time Frame: Day -1, Up to Day 84 ]
• Change from Eligibility (Day -1) in CNV size at each visit [ Time Frame: Day -1, Up to Day 84 ]
• The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume] (Cmax) [ Time Frame: Day 28, Day 84 ]
  Contingent upon observed serum concentration levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Exudative Age-Related Macular Degeneration

Intervention

• Drug: LHA510 ophthalmic suspension
• Drug: LHA510 vehicle
  Inactive ingredients used as a placebo comparator
• Drug: Ranibizumab ophthalmic solution
  For intravitreal (IVT) injection
  Other Name: Lucentis®

Study Arms

• Experimental: LHA510
  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.
  Interventions:

  • Drug: LHA510 ophthalmic suspension
  • Drug: Ranibizumab ophthalmic solution
• Placebo Comparator: Vehicle
  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.
  Interventions:

  • Drug: LHA510 vehicle
  • Drug: Ranibizumab ophthalmic solution

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 13, 2017): 136
• Original Estimated Enrollment (submitted: February 2, 2015): 60
• Actual Study Completion Date: October 18, 2016
• Actual Primary Completion Date: September 15, 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02355028
• Other Study ID Numbers: LHA510-2201
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

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.

• Current Responsible Party: Alcon Research ( Alcon, a Novartis Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Alcon, a Novartis Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Scientist, CA CSI, ID/Multi-TA; Novartis Institutes for BioMedical Research, Inc.

• PRS Account: Alcon Research
• Verification Date: November 2017