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NCT02355028

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

Completed Phase 2 Results posted Last updated 2 July 2018
What this trial tests

Phase 2 trial testing LHA510 ophthalmic suspension in Exudative Age-Related Macular Degeneration in 136 participants. Completed in 18 October 2016.

Timeline
3 March 2015
Primary endpoint
15 September 2016
18 October 2016

Quick facts

Lead sponsorAlcon, a Novartis Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment136
Start date3 March 2015
Primary completion15 September 2016
Estimated completion18 October 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Alcon, a Novartis Company — full company profile →

Who can join

Adults 50 to 90, any sex, with Exudative Age-Related Macular Degeneration. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Subjects With Positive LUCENTIS® Retreatment Status at Day 84 Primary · 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.

GroupValue95% CI
LHA51025
Vehicle25
Time to First LUCENTIS® Retreatment Need Identification up to Day 84 Secondary · 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.

Day 14
GroupValue95% CI
LHA5100
Vehicle0
Day 28
GroupValue95% CI
LHA5105
Vehicle8
Day 56
GroupValue95% CI
LHA51016
Vehicle11
Day 84
GroupValue95% CI
LHA5104
Vehicle6
Number of LUCENTIS® Retreatment Needs Identified Required up to Day 84 Secondary · 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

0 retreatment injections
GroupValue95% CI
LHA5108
Vehicle12
1 retreatment injection
GroupValue95% CI
LHA51018
Vehicle18
2 retreatment injections
GroupValue95% CI
LHA5106
Vehicle6
3 retreatment injections
GroupValue95% CI
LHA5101
Vehicle1
Number of Subjects Requiring LUCENTIS® Retreatment at Days 28 and 56 Secondary · 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.

Day 28
GroupValue95% CI
LHA5105
Vehicle8
Day 56
GroupValue95% CI
LHA51021
Vehicle19
Change From Randomization Visit (Day -1) in Central Subfield Thickness Total (CSFTtot) at All Visits at the Study Site Secondary · 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.

Day 14
GroupValue95% CI
LHA510-46.9± 8.40
Vehicle-43.0± 7.93
Day 28
GroupValue95% CI
LHA510-38.6± 7.42
Vehicle-28.9± 7.00
Day 56
GroupValue95% CI
LHA51011.3± 10.01
Vehicle1.0± 9.45
Day 84
GroupValue95% CI
LHA510-16.8± 8.92
Vehicle-12.2± 8.42
Change From Randomization Visit (Day -1) in Best Corrected Visual Acuity (BCVA) at All Visits at the Study Site Secondary · 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.

Day 14
GroupValue95% CI
LHA5101.3± 0.80
Vehicle1.6± 0.75
Day 28
GroupValue95% CI
LHA5101.7± 0.89
Vehicle2.5± 0.84
Day 56
GroupValue95% CI
LHA510-0.5± 1.28
Vehicle2.3± 1.21
Day 84
GroupValue95% CI
LHA510-1.7± 1.59
Vehicle2.2± 1.50
Change From Randomization Visit (Day -1) in Central Subfield Thickness, Neuro-retina (CSFTnr) by Visit Secondary · 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.

Day 28
GroupValue95% CI
LHA510-16.6± 22.62
Vehicle-15.1± 38.21
Day 84
GroupValue95% CI
LHA510-4.1± 35.34
Vehicle-8.8± 36.75
Change From Randomization Visit (Day -1) in Lesion Thickness by Visit Secondary · 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.

Day 28
GroupValue95% CI
LHA510-1.9± 38.05
Vehicle6.9± 43.66
Day 84
GroupValue95% CI
LHA5101.4± 26.46
Vehicle6.9± 43.96
Change From Randomization Visit (Day -1) in Subretinal Fluid - Foveal Involvement (SRFfi) Thickness by Visit Secondary · 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.

Day 28
GroupValue95% CI
LHA510-18.5± 44.67
Vehicle-11.0± 34.73
Day 84
GroupValue95% CI
LHA510-14.1± 54.08
Vehicle-5.9± 31.33
Change From Randomization Visit (Day -1) in Pigment Epithelial Detachment - Foveal Involvement (PEDfi) Thickness by Visit Secondary · 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.

Day 28
GroupValue95% CI
LHA510-0.3± 38.92
Vehicle-13.3± 43.23
Day 84
GroupValue95% CI
LHA510-0.2± 33.33
Vehicle-7.6± 47.25
Change From Randomization Visit (Day -1) in Total Lesion Size by Visit Secondary · 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.

GroupValue95% CI
LHA510-0.3± 1.71
Vehicle0.5± 1.81
Change From Randomization Visit (Day -1) in CNV Size by Visit Secondary · 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.

GroupValue95% CI
LHA510-0.6± 2.00
Vehicle0.5± 1.71

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected from time of consent for the duration of a subject's participation in the study (up to 177 days). AEs are reported as pre-treatment, treatment-emergent, and post-treatment.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pre-treatment
Serious: 0/136 (0%)
Deaths: 0/136
LHA510
Serious: 1/46 (2%)
Deaths: 0/46
Vehicle
Serious: 0/45 (0%)
Deaths: 0/45
Post-treatment LHA510
Serious: 1/46 (2%)
Deaths: 0/46
Post-treatment Vehicle
Serious: 0/45 (0%)
Deaths: 0/45

Serious adverse events (4 terms)

ReactionSystemPre-treatmentLHA510VehiclePost-treatment LHA510Post-treatment Vehicle
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Cardiac failure congestiveCardiac disorders
Bronchial hyperreactivityRespiratory, thoracic and mediastinal disorders
Other adverse events (9 terms — click to expand)

ReactionSystemPre-treatmentLHA510VehiclePost-treatment LHA510Post-treatment Vehicle
Corneal opacityEye disorders
Corneal oedemaEye disorders
Vision blurredEye disorders
Eye irritationEye disorders
KeratopathyEye disorders
Vital dye staining cornea presentInvestigations
Eye painEye disorders
Visual acuity reducedEye disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Acute myocardial infarction, Angina pectoris, Cardiac failure congestive, Bronchial hyperreactivity.

Data from ClinicalTrials.gov NCT02355028 adverse events section.

Sponsor's own description

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).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Topical Drug Delivery to the Posterior Segment of the Eye: Addressing the Challenge of Preclinical to Clinical Translation.
    Rodrigues GA, Lutz D, Shen J, Yuan X, et al · · 2018 · cited 86× · PMID 30374744 · DOI 10.1007/s11095-018-2519-x
  2. Recent Advances in Age-Related Macular Degeneration Therapies.
    Fabre M, Mateo L, Lamaa D, Baillif S, et al · · 2022 · cited 68× · PMID 36014339 · DOI 10.3390/molecules27165089
  3. Anti-angiogenic Therapy for Retinal Disease.
    Paulus YM, Sodhi A. · · 2017 · cited 43× · PMID 27783271 · DOI 10.1007/164_2016_78
  4. A hypotonic gel-forming eye drop provides enhanced intraocular delivery of a kinase inhibitor with melanin-binding properties for sustained protection of retinal ganglion cells.
    Kim YC, Hsueh HT, Shin MD, Berlinicke CA, et al · · 2022 · cited 19× · PMID 33900546 · DOI 10.1007/s13346-021-00987-6
  5. Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration.
    Fei X, Jung S, Kwon S, Kim J, et al · · 2024 · cited 6× · PMID 38902481 · DOI 10.1007/s12272-024-01503-3
  6. Rethinking the potential and necessity of drug delivery systems in neovascular age-related macular degeneration therapy.
    Huang X, Zhang L, Fu Y, Zhang M, et al · · 2023 · cited 3× · PMID 37288355 · DOI 10.3389/fbioe.2023.1199922

Verify or expand the search:

Other recruiting trials for Exudative Age-Related Macular Degeneration

Currently open trials in the same condition.

Other Alcon, a Novartis Company trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing