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 Degeneratio

Exclusion Criteria38

• 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
• 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