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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Age-Related Macular Degeneration
• Intervention / Treatment: Drug: Placebo; Drug: Iptacopan (LNP023)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200080
    • Novartis Investigative Site
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research and Development Center LLC
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
• United States
  • California
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Huntington Beach, California, United States, 92647
      • Salehi Retina Institute
    • Rancho Cordova, California, United States, 95670
      • Martel Eye Medical Group
    • Sacramento, California, United States, 95841
      • Retinal Consultants Medical Group Inc
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
  • Colorado
    • Durango, Colorado, United States, 81303
      • Southwest Retina Research Center
  • Florida
    • Deerfield Beach, Florida, United States, 33064
      • Advanced Research LLC
    • Delray Beach, Florida, United States, 33484
      • Retina Center Of South Florida
    • Saint Petersburg, Florida, United States, 33711
      • Retina Vitreous Associates of Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46280
      • Midwest Eye Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70115 8139
      • Retina Associates New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Retina Care Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Opthamalic Consultants of Boston
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Envision Ocular LLC
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke Eye Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Retina Northwest PC
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
  • Texas
    • Austin, Texas, United States, 78793
      • Austin Research Center for Retina
    • Bellaire, Texas, United States, 77401
      • Retina Consultants TX Rsrch Ctr
    • Dallas, Texas, United States, 75231
      • Retina Foundation
    • Fort Worth, Texas, United States, 76104
      • Texas Retina Associates
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iptacopan (LNP023); Iptacopan (LNP023) oral use capsules	Drug: Iptacopan (LNP023); oral capsules
Placebo Comparator: Placebo; Placebo matched to study drug, oral use capsules	Drug: Placebo; oral capsules

What is the study measuring?

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
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
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 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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 2, 2026

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 9, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: OCT; AMD; Neovascular AMD; Age-related macular degeneration; Macular degeneration; wet macular degeneration; retina damage; dry macular degeneration; vision loss, macula damage; Best Corrected Visual Acuity
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration
• Other Study ID Numbers: CLNP023E12201; 2021-001797-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No