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NCT07215390PHASE2Recruiting

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

Apellis Pharmaceuticals, Inc.

Start Date

6/23/2025

Completion Date

11/1/2027

Summary

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

Eligibility Criteria

Age Range: 60 years to No maximum

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: * Total GA area must be ≥2.5 and ≤17.5 mm2 (1-7 disk areas \[DA\]) * If GA is multifocal, at least 1 focal lesion must be ≥1.25 mm2 (0.5 DA), with the overall aggregate area of GA as specified above in 7a * The entire GA lesion must be completely visualized in the field of view of the OCT, with the GA RPE lesion border \>500 µm from the edge of the imaging window or any areas of peripapillary atrophy. * Nonsubfoveal lesion with border of GA lesion not encroaching center of the fovea. Distance of GA RPE lesion from center of the fovea \>0 based on OCT imaging. * Presence of any pattern of hyperautofluorescence based on FAF imaging in the junctional zone of GA. Absence of hyperautofluorescence (ie, pattern = none) is exclusionary. * Documented evidence of vaccination within 5 years prior to screening, or willing to initiate vaccinations at least 14 days prior to dosing against: * Streptococcus pneumoniae (with a pneumococcal conjugate vaccine 15 \[PCV15\] or 20 \[PCV20\] or with pneumococcal polysaccharide vaccine 23 \[PPSV23\]), * Haemophilus influenzae (type B) (with Hib vaccine), * Neisseria meningitidis types A, C, W, and Y (with a quadrivalent meningococcal conjugate vaccine \[eg, Menactra or MenQuadfi\]), and * Neisseria meningitidis type B (with a meningococcal serogroup B vaccine \[eg, Bexsero\]) Female participants must be: * Women of non-childbearing potential (WONCBP), or * Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study and refrain from breastfeeding for the duration of the study (see Section 10.9.5.1) 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: 1. Uncontrolled, clinically relevant history of any gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, or cancer 2. History or presence of hepatic cirrhosis or other liver disease that may increase the risk of drug-induced liver injury 3. History or presence of systemic autoimmune disorders, with the exception of well controlled Hashimoto's thyroiditis 4. 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 5. Clinically meaningful abnormalities on diagnostic and laboratory testing must be adjudicated by the sponsor's medical monitor and include: 1. 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 2. 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 3. 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 6. 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 7. History or presence of recurrent or unexplained infections, HIV infection, hepatitis B, hepatitis C, or meningococcal infection 8. 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 9. Evidence of ongoing drug or alcohol abuse or dependence, in the opinion of the investigator 10. Intention to donate sperm during this study or within 90 days after the last dose of study drug 11. Prior administration of APL-3007 12. Participation in an investigational product or medical device study within 5 half-lives of the investigational product before the screening visit 13. 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 14. 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 15. Has received a live vaccination (excluding seasonal flu vaccination) within 30 days prior to the first dose administration 16. Women who are pregnant or breastfeeding 17. 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. 18. GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy in either eye 19. 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 20. 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. 21. History of IVT injection in the study eye within 3 months prior to the screening visit, with the exception of IVT Syfovre 22. 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 23. History of laser therapy in the macular region 24. 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

Interventions

DRUG

APL-3007, pegcetacoplan (APL-2)

DRUG

APL-3007, pegcetacoplan (APL-2)

OTHER

Placebo, Syfovre

Interested in This Trial?

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Conditions

Geographic Atrophy Secondary to Age-related Macular Degeneration

Locations

Associated Retina Consultants (01065)

Gilbert, Arizona 85297

United States

Barnet Dulaney Perkins Eye Center (01018)

Mesa, Arizona 85206

United States

Associated Retina Consultants - Phoenix

Phoenix, Arizona 85020

United States

Retinal Research Institute, LLC (01021)

Phoenix, Arizona 85053

United States

Research Network Arizona

Scottsdale, Arizona 46214

United States

California Retina Consultants (CRC) - Bakersfield Office

Bakersfield, California 93309

United States

Retinal Diagnostic Center

Campbell, California 95008

United States

The Retina Partners - Encino

Encino, California 07003

United States

Retina Consultants of Orange County - Fullerton Office

Fullerton, California 93825

United States

Salehi Retina Institute, Inc dba Retina Associate or Southern California (01034)

Huntington Beach, California 92647

United States

Salehi Retina Institute, Inc. Dba Retina Associates of Southern California (01034)

Huntington Beach, California 92647

United States

California Retina Consultants (01054)

Oxnard, California 93036

United States

Retina Consultants San Diego

Poway, California 92064

United States

Orange County Retina Medical Group

Santa Ana, California 92705

United States

Retina Macula Institute

Torrance, California 90503

United States

Bay Area Retina Associates - Walnut Creek

Walnut Creek, California 94598

United States

Colorado Retina Associates, PLLC

Lakewood, Colorado 80228

United States

Advanced Vision Research Institute

Longmont, Colorado 80503

United States

Connecticut Eye Consultants, PC (01074)

Danbury, Connecticut 06810

United States

ClearVista Clinical Research, LLC (01096)

Bayonet Point, Florida 34667

United States

Advance Retina Institute

Bonita Springs, Florida 34134

United States

Florida Retina Institute (01053)

Orlando, Florida 32806

United States

Florida Retina Institute - Orlando (01053)

Orlando, Florida 32806

United States

Retina Specialty Institute - Pensacola

Pensacola, Florida 32503

United States

Eye Associates of Pinellas (01020)

Pinellas Park, Florida 33782

United States

Retina Vitreous Associates of Florida (RVA) - Saint Petersburg

St. Petersburg, Florida 33711

United States

Retina Vitreous Associates of Florida

Tampa, Florida 33617

United States

Center for Retina and Macular Disease (01026)

Winter Haven, Florida 33880

United States

Southeast Retina Center

Augusta, Georgia 30909

United States

Illinois Retina Associates, S.C. - Oak Park (01061)

Oak Park, Illinois 60304

United States

Midwest Eye Institute (01066)

Carmel, Indiana 46032

United States

Vision Research Solutions

Indianapolis, Indiana 21044

United States

Advancing Research International. LLC (01090)

Indianapolis, Indiana 46214

United States

Retina Consultants P.C.

Indianapolis, Indiana 46214

United States

Retina Associates New Orleans - Jefferson Parish Location

Metairie, Louisiana 70001

United States

The Retina Care Center

Baltimore, Maryland 21209

United States

The Retina Group of Washington (01089)

Chevy Chase, Maryland 29902

United States

Cumberland Valley Retina Consultants (CVRC)

Hagerstown, Maryland 21740

United States

Retina Specialists

Towson, Maryland 21204

United States

Mississippi Retina Associates

Madison, Mississippi 39110

United States

Envision Ocular, LLC (01027)

Bloomfield, New Jersey 07003

United States

Mid Atlantic Retina (01039)

Cherry Hill, New Jersey 08034

United States

NJ Retina (01031)

Edison, New Jersey 08820

United States

NJ Retina (01030)

Toms River, New Jersey 08755

United States

Vision Research Center Eye Associates of New Mexico (01023)

Albuquerque, New Mexico 87109

United States

Long Island Vitreoretinal Consultants (01050)

Great Neck, New York 11021

United States

Long Island Vitreoretinal Consultants - Westbury

Long Island City, New York 11590

United States

Retina Assocaites of Cleveland, Inc (01048)

Cleveland, Ohio 44122

United States

Retina Associates of Cleveland

Cleveland, Ohio 44130

United States

Verum Research, LLC

Eugene, Oregon 97401

United States

EyeHealth Northwest

Portland, Oregon 97225

United States

EyeHealth Northwest (01006)

Portland, Oregon 97228

United States

Cascade Medical Research Institute, LLC (01070)

Springfield, Oregon 97477

United States

Eye Care Specialists

Kingston, Pennsylvania 18704

United States

Mid Atlantic Retina - Philadelphia (01017)

Philadelphia, Pennsylvania 19107

United States

Charleston Neuroscience Institute (01037)

Beaufort, South Carolina 29902

United States

Retina Consultants of Carolina, PA (01073)

Greenville, South Carolina 29605

United States

Charleston Neuroscience Institute LLC - Ladson

Ladson, South Carolina 29456

United States

Charleston Neuroscience Institute, LLC - Mount Pleasant (01051)

Mt. Pleasant, South Carolina 29464

United States

Ophthalmology Ltd. (01084)

Sioux Falls, South Dakota 57108

United States

Tennessee Retina, PC (01063)

Nashville, Tennessee 37203

United States

Retina Consultants of Texas - Abilene (01035)

Abilene, Texas 79606

United States

Austin Retina Associates

Austin, Texas 78705

United States

Retina Consultants of Texas - Bellaire (01067)

Bellaire, Texas 77401

United States

Texas Retina Associates

Dallas, Texas 75231

United States

Retina Consultants of Texas - Katy

Katy, Texas 77494

United States

Valley Retina Institute- McAllen (01076)

McAllen, Texas 78503

United States

Austin Retina Associates - Round Rock (01032)

Round Rock, Texas 78681

United States

Retina Consultants of Texas - San Antonio Medical Center

San Antonio, Texas 78240

United States

Austin Retina Associate (01046)

San Marcos, Texas 78666

United States

Retina Consultants of Texas (01055)

Schertz, Texas 78154

United States

Retina Center of Texas - Southlake

Southlake, Texas 76092

United States

Retina Consultants of Texas - The Woodlands

The Woodlands, Texas 73384

United States

Tyler Retina Consultants

Tyler, Texas 75703

United States

Retina Associates of Utah (01052)

Salt Lake City, Utah 84107

United States

Salt Lake Retina (01044)

West Jordan, Utah 84088

United States

Piedmont Eye Center (01097)

Lynchburg, Virginia 24502

United States

University of Wisconsin Health - University Station Clinic

Madison, Wisconsin 53705

United States