A Masked, Placebo-controlled Study to Assess Iptacopan in Age-related Macular Degeneration

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of Iptacopan to prevent conversion of early or intermediate age-related macular degeneration (AMD) eyes to new incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) or late AMD.

Detailed Description
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This is a multicenter, randomized, participant and investigator masked, placebo controlled, proof-of-concept study to assess the safety and efficacy of Iptacopan (LNP023) in participants with early to intermediate age-related macular degeneration in one eye and neovascular age-related macular degeneration in the other eye. All enrolled participants must have early/intermediate AMD in one eye, with at least one high risk optical coherence tomography (OCT) feature (study eye) and neovascular AMD in the other eye (fellow eye). Participants who meet all of the eligibility criteria will be randomized at the Baseline/Day 1 visit in a 1:1 ratio into one of two treatment arms: Iptacopan (LNP023) oral capsules Placebo oral capsules Approximately 146 participants (73 per arm) will be treated worldwide.

Official Title
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A Randomized, Participant and Investigator Masked, Placebo-controlled, Multicenter, Proof-of-concept Study to Assess the Safety and Efficacy of LNP023 (Iptacopan) in Patients With Early and Intermediate Age-related Macular Degeneration

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Iptacopan (LNP023)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥ 50 years of age Diagnosis of early or intermediate age-related macular degeneration (AMD) in the study eye as determined by the investigator on fundus examination Study eye (early/intermediate AMD eye) must have at least one high risk optical coherence tomography (OCT) feature (as defined by a central reading center). Diagnosis of neovascular AMD (nAMD) in the fellow eye as determined by the investigator. Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection are required prior to the start of the treatment with LNP023. If not received previously, vaccination against Haemophilius influenzae infection should be given, if available and according to local regulations. Exclusion Criteria: History or current diagnosis of ECG abnormalities indicating significant safety risk, such as clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia and clinically significant second or third degree atrioventricular block (AV block) without a pacemaker. History of familial long QT syndrome or known family history of Torsades de Pointes History of stroke or myocardial infarction during the 6-month period prior to Baseline/Day 1, any current clinically significant arrhythmias, or any advanced cardiac or severe pulmonary hypertension History of end stage kidney disease requiring dialysis or renal transplant History of malignancy of any organ system History of solid organ or bone marrow transplantation History of recurrent meningitis or history of meningococcal infections despite vaccination History of immunodeficiency diseases, including a positive Human Immunodeficiency Virus test result at Screening Active Hepatitis B (HBV) or Hepatitis C (HCV) infection History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes or clinically relevant sensitivity to fluorescein dye as assessed by the Investigator. Evidence of cRORA or exMNV in the study eye based on multimodal imaging as determined by the central reading center. Participants who have current active TB as evidenced by clinical, radiographic and laboratory tests.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a multicenter, randomized, participant and investigator masked, placebo controlled, proof-of-concept study to assess the safety and efficacy of LNP023 in participants with early to intermediate age-related macular degeneration (e/iAMD) in one eye and neovascular age-related macular degeneration (nAMD) in the other eye.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iptacopan (LNP023)<br>Iptacopan (LNP023) oral use capsules | Drug: Iptacopan (LNP023)<br>* oral capsules<br>|
| Placebo Comparator: Placebo<br>Placebo matched to study drug, oral use capsules | Drug: Placebo<br>* oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of new incomplete retinal pigment epithelium & outer retinal atrophy or late age-related macular degeneration (AMD) in the early/intermediate AMD eye as determined by optical coherence tomography (OCT) & supported by multimodal imaging | OCT and other imaging will be performed using spectral domain OCT or swept source OCT machines | Baseline/Day 1 through Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of ocular and non-ocular adverse events (AEs) | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. | Baseline/Day 1 through Month 24 | 
| Change in Early Treatment Diabetic Retinopathy Study (ETDRS) (Standard Luminance) best corrected visual acuity (BCVA) scores in the early/intermediate AMD eye | Best corrected visual acuity (BCVA) will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. The number of letters read correctly, for each eye, will be recorded. Participants at sites in some countries may conduct BCVA testing using numerical charts rather than letter charts. | Baseline/Day 1 through Month 24 | 
| Change in ETDRS low luminance visual acuity (LLVA) scores in the early/intermediate AMD eye | ETDRS low luminance visual acuity (LLVA) scores will be measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart. The number of letters read correctly, for each eye, will be recorded. Participants at sites in some countries may conduct BCVA testing using numerical charts rather than letter charts. | Baseline/Day 1 through Month 24 | 
| Change in contrast sensitivity (CS) scores in the early/intermediate AMD eye | Pelli-Robson contrast sensitivity measurements will be performed using a Pelli-Robson contrast sensitivity wall chart and recording the number of correct letters read. | Baseline/Day 1 through Month 24 | 
| Change in Standard luminance manifold contrast vision meter contrast sensitivity (MCVM-CS) scores in the early/intermediate AMD eye | MCVM contrast sensitivity measurements will be performed using an automated device that uses an adaptive algorithm to rapidly measure a contrast sensitivity function in 5-10 minutes. | Baseline/Day 1 through Month 24 | 
| Pharmacokinetics - concentrations of LNP023 related to trough samples | Bioanalytical determination of plasma LNP023 concentrations related to trough samples using a LC-MS (mass spectrometry) method. | Baseline/Day 1 through Month 24 | 
| Change in low luminance manifold contrast vision meter (MCVM) contrast sensitivity scores in the early/intermediate AMD eye | MCVM contrast sensitivity measurements will be performed using an automated device that uses an adaptive algorithm to rapidly measure a contrast sensitivity function in 5-10 minutes. | Baseline/Day 1 through Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, Age-related macular degeneration, Macular degeneration, vision loss, macula damage, retina damage, dry macular degeneration, wet macular degeneration, Best Corrected Visual Acuity, Neovascular AMD, OCT