Clinical trial NCT05230537: A Masked, Placebo-controlled Study to Assess Iptacopan in Age-related Macular Degeneration
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Age-Related Macular Degeneration
Keywords: Age-related macular degeneration
Macular degeneration
vision loss, macula damage
retina damage
dry macular degeneration
wet macular degeneration
AMD
Best Corrected Visual Acuity
Neovascular AMD
OCT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-02-09
Enrollment: 146
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline/Day 1 through Month 24
Secondary outcomes:
measure: The incidence of ocular and non-ocular adverse events (AEs)
timeFrame: Baseline/Day 1 through Month 24
measure: Change in Early Treatment Diabetic Retinopathy Study (ETDRS) (Standard Luminance) best corrected visual acuity (BCVA) scores in the early/intermediate AMD eye
timeFrame: Baseline/Day 1 through Month 24
measure: Change in ETDRS low luminance visual acuity (LLVA) scores in the early/intermediate AMD eye
timeFrame: Baseline/Day 1 through Month 24
measure: Change in contrast sensitivity (CS) scores in the early/intermediate AMD eye
timeFrame: Baseline/Day 1 through Month 24
measure: Change in Standard luminance manifold contrast vision meter contrast sensitivity (MCVM-CS) scores in the early/intermediate AMD eye
timeFrame: Baseline/Day 1 through Month 24
measure: Pharmacokinetics - concentrations of LNP023 related to trough samples
timeFrame: Baseline/Day 1 through Month 24
measure: Change in low luminance manifold contrast vision meter (MCVM) contrast sensitivity scores in the early/intermediate AMD eye
timeFrame: Baseline/Day 1 through Month 24
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Huntington Beach
country: United States
facility: Salehi Retina Institute
state: California
city: Rancho Cordova
country: United States
facility: Martel Eye Medical Group
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group, Inc
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants .
state: California
city: Durango
country: United States
facility: Southwest Retina Research Center
state: Colorado
city: Deerfield Beach
country: United States
facility: Advanced Research LLC Research
state: Florida
city: Deerfield Beach
country: United States
facility: Advanced Research LLC
state: Florida
city: Delray Beach
country: United States
facility: Retina Center Of South Florida
state: Florida
city: Saint Petersburg
country: United States
facility: Retina Vitreous Associates of Florida
state: Florida
city: Indianapolis
country: United States
facility: Midwest Eye Institute Research
state: Indiana
city: New Orleans
country: United States
facility: Retina Associates New Orleans .
state: Louisiana
city: Baltimore
country: United States
facility: Retina Care Center Research
state: Maryland
city: Boston
country: United States
facility: Opthamalic Consultants of Boston
state: Massachusetts
city: Bloomfield
country: United States
facility: Envision Ocular LLC
state: New Jersey
city: New York
country: United States
facility: Vitreous Retina Macula Consultants Research
state: New York
city: Durham
country: United States
facility: Duke Eye Center Research
state: North Carolina
city: Portland
country: United States
facility: Retina Northwest PC .
state: Oregon
city: Kingston
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
city: Austin
country: United States
facility: Austin Research Center for Retina .
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants TX Rsrch Ctr
state: Texas
city: Dallas
country: United States
facility: Retina Foundation
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston PA .
state: Texas
city: Harbin City
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center LLC
city: Gloucester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: