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A Phase 2, Randomized, Placebo-controlled, Multicenter, Masked Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Multidose APL-3007 in Combination with Syfovre/Pegcetacoplan (APL-2) in Patients Diagnosed with Geographic Atrophy Secondary to Age-Related Macular Degeneration
Enrollment
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Volunteers
Inclusion criteria
The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with better normal luminance visual acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be used as the study eye.
Aged ≥60 years
Clinical diagnosis of GA of the macula secondary to AMD in one or both eyes, as determined by the investigator and confirmed by the reading center
NL-BCVA of 50 letters or better using early treatment diabetic retinopathy study (ETDRS) charts (approximately 20/100 Snellen equivalent)
Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit the collection of good quality images in the study eye as determined by the investigator
Prior treatment for GA in the study eye using Syfovre at 6-8 weeks interval for at least 6 months but no more than 24 months. Participants will be included if the participant has had at least 2 Syfovre injections in the last 6 months before screening.
The GA lesion in at least 1 eye (designated as the study eye) must meet the following criteria as determined by the central reading center's OCT based RPE assessment of imaging at screening:
Documented evidence of vaccination within 5 years prior to screening, or willing to initiate vaccinations at least 14 days prior to dosing against:
Female participants must be:
Male participants must be surgically sterile or must agree to use highly effective contraception from screening through the duration of the study
Willing and able to provide informed consent and adhere to the study visit schedule and other protocol requirements
Exclusion criteria
Uncontrolled, clinically relevant history of any gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, or cancer
History or presence of hepatic cirrhosis or other liver disease that may increase the risk of drug-induced liver injury
History or presence of systemic autoimmune disorders, with the exception of well controlled Hashimoto's thyroiditis
History of allergy, hypersensitivity, or serious adverse reaction to siRNA therapy or related compounds, or allergy to any of the components of the study drug
Clinically meaningful abnormalities on diagnostic and laboratory testing must be adjudicated by the sponsor's medical monitor and include:
Cardiac
Sustained resting heart rate outside of range of 40 to 100 beats/minute, or a heart rhythm that is not sinus rhythm, confirmed on repeat testing within a maximum of 30 minutes, at screening
History or evidence of hereditary short QT syndrome
Fridericia's corrected QT interval (QTcF) >480 milliseconds, or the PR interval outside the range of 120 to 220 milliseconds, confirmed on repeat testing within a maximum of 30 minutes at screening
Any clinically relevant features of acute coronary syndrome (unstable angina, myocardial infarction)
Any other ECG parameters outside of age-adjusted normative range
Hepatic
AST or ALT >1.3 × ULN
Total bilirubin >1.1 × ULN
Any 2 LFTs >1.1 × ULN
Any other LFT parameters outside of age-adjusted normative range
Renal
Estimated glomerular filtration rate of less than <45 mL/min/m2 as calculated by the Chronic Kidney Disease-Epidemiology Collaboration (CKD- EPI) creatinine equation for adults
Any other renal function parameters outside of age-adjusted normative range
History or presence of malignancy (except history of basal or squamous cell carcinoma of the skin) that has not been successfully treated ≥1 year prior to enrollment
History or presence of recurrent or unexplained infections, HIV infection, hepatitis B, hepatitis C, or meningococcal infection
Participants with fever (defined as temperature >100.4 °F/38 °C) or any acute infection (including COVID-19 infection or infection requiring antibiotic treatment) within 30 days of screening until dosing
Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of the investigator
Intention to donate sperm during this study or within 90 days after the last dose of study drug
Prior administration of APL-3007
Participation in an investigational product or medical device study within 5 half-lives of the investigational product before the screening visit
Has poor peripheral venous access or any abnormal skin conditions or potentially obscuring tattoos, pigmentation, or lesions in the area intended for SC injection that would interfere with SC injections or assessments of injection local tolerability
Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the investigator or medical monitor(s), unacceptably increase the participant's risk by participating in the study
Has received a live vaccination (excluding seasonal flu vaccination) within 30 days prior to the first dose administration
Women who are pregnant or breastfeeding
Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the treatment period unlikely, or would make the participant an unsafe study candidate
Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.
GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye
Any history of CNV (active or nonexudative/quiescent) in the study eye associated with AMD or any other cause, including any evidence of RPE rips, double layer sign, or evidence of neovascularization anywhere based on SD-OCT imaging and fluorescein angiography as assessed by the reading center
Presence of an active ocular disease that, in the opinion of the investigator, compromises or confounds visual function, including but not limited to, uveitis, other macular diseases (eg, clinically significant epiretinal membrane, full thickness macular hole or uncontrolled glaucoma/ocular hypertension); benign conditions in the opinion of the investigator such as peripheral retina dystrophy are not exclusionary.
History of IVT injection in the study eye within 3 months prior to the screening visit, with the exception of IVT Syfovre
History of any previous investigational product for GA treatment in either eye within 3 months (or 5 half-lives of the investigational drug, whichever is longer) prior to the screening visit
History of laser therapy in the macular region
Any ocular condition other than GA secondary to AMD that may require surgery or medical intervention during the study period or, in the opinion of the investigator, could compromise visual function during the study period
Primary purpose
Allocation
Interventional model
Masking
240 participants in 3 patient groups, including a placebo group
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Central trial contact
Apellis Clinical Trial Information Line
Data sourced from clinicaltrials.gov
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