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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05230537

Collaborator

(none)

146

Enrollment

Locations

Arms

58.6

Anticipated Duration (Months)

24.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Age-Related Macular Degeneration	Drug: Iptacopan (LNP023) Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

146 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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 (Participant, Investigator, Outcomes Assessor)

Masking Description:

Investigator and Participant

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 17, 2022

Anticipated Primary Completion Date :

Jan 7, 2027

Anticipated Study Completion Date :

Jan 7, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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 [Baseline/Day 1 through Month 24]
OCT and other imaging will be performed using spectral domain OCT or swept source OCT machines.

Secondary Outcome Measures

The incidence of ocular and non-ocular adverse events (AEs) [Baseline/Day 1 through Month 24]
The occurrence of adverse events must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, accompanied by the information (as far as possible) on the severity, relationship to study treatment, duration, whether it is a serious adverse event, the action taken and the outcome.
Change in Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) scores in the early/intermediate AMD eye [Baseline/Day 1 through Month 24]
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.
Change in ETDRS low luminance visual acuity (LLVA) scores in the early/intermediate AMD eye [Baseline/Day 1 through Month 24]
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.
Change in contrast sensitivity (CS) scores in the early/intermediate AMD eye [Baseline/Day 1 through Month 24]
Pelli-Robson contrast sensitivity measurements will be performed using a Pelli-Robson contrast sensitivity wall chart and recording the number of correct letters read.
Change in low luminance contrast sensitivity (LLCS) scores in the early/intermediate AMD eye [Baseline/Day 1 through Month 24]
Low luminance Pelli-Robson contrast sensitivity measurements will be performed using a Pelli-Robson contrast sensitivity wall chart and recording the number of correct letters read.
LNP023 pharmacokinetics parameters including but not limited to Tmax [Baseline/Day 1 through Month 24]
Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time).
LNP023 pharmacokinetics parameters including but not limited to Cmax [Baseline/Day 1 through Month 24]
Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass × volume-1)
LNP023 pharmacokinetics parameters including but not limited to area under the curve last (AUClast) [Baseline/Day 1 through Month 24]
AUClast is the AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1)
LNP023 pharmacokinetics parameters including but not limited to area under the curve to infinity (AUCinf) [Baseline/Day 1 through Month 24]
AUCinf is the AUC from time zero to infinity (mass × time × volume-1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Concomitant medical or ocular conditions which could compromise visual acuity, require planned medical or surgical intervention during the study period, preclude scheduled study visits, completion of the study, or safe administration of the investigational product, including intraocular surgery, cataract and vitreoretinal surgery in the study eye within 3 months prior to Baseline/Day 1 and the presence of significant media opacity, eye movement disorder (nystagmus), severe ptosis, extraocular motility restriction or head tremor.
History of clinically significant electrocardiogram (ECG) abnormalities, or any of the following ECG abnormalities at screening or Baseline/Day 1 visit:
QT interval corrected by Fridericia's formula (QTcF) >450 msec (males)
QTcF >460 msec (females)
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 kidney failure including end stage renal 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
Chronic infection with Hepatitis B or Hepatitis C.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Sacramento	California	United States	95841
2	Novartis Investigative Site	Coral Springs	Florida	United States	33067
3	Novartis Investigative Site	Indianapolis	Indiana	United States	46280
4	Novartis Investigative Site	Kingston	Pennsylvania	United States	95403
5	Novartis Investigative Site	Dallas	Texas	United States	75231
6	Novartis Investigative Site	Fort Worth	Texas	United States	76104