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APL-2

Phase 3

Geographic Atrophy | Small molecule | Ophthalmology |Apellis Pharmaceuticals, Inc.|Last Updated: Feb 13, 2025

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment1,258

FDA Designations

No designations recorded

Clinical trial landscape

APL-2 · 5 trials · 9 indications

Phase 3 3Phase 2 2
NCT04085601A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNHParoxysmal Nocturnal Hemoglobinuria
COMPLETED53 Analytics
NCT03525600Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular DegenerationGeographic Atrophy
COMPLETED621 Analytics
NCT03525613A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular DegenerationGeographic Atrophy
COMPLETED637 Analytics
PHASE3COMPLETED
A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With PNH
Paroxysmal Nocturnal HemoglobinuriaUnlock trial analytics
PHASE3COMPLETED
Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration
Geographic AtrophyUnlock trial analytics
PHASE3COMPLETED
A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration
Geographic AtrophyUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Subjects Who Achieved Hemoglobin (Hb) Stabilization
From Baseline (Day 1) up to Week 26

The Hb stabilization was defined as avoidance of a \>1 gram per deciliter (g/dL) decrease in Hb concentration from Baseline in the absence of transfusion through Week 26.

Change From Baseline in Lactate Dehydrogenase (LDH) Concentration At Week 26
Baseline (Day 1) and Week 26

The LDH concentration was analyzed using an analysis of covariance (ANCOVA) model with a last observation carried forward (LOCF) and a baseline observation carried forward (BOCF) approach for handling missing data. Baseline was defined as average of measurements prior to first dose of pegcetacoplan or on or prior to randomization of SoC. Post baseline missing values are imputed using multiple imputation method with Markov Chain Mont Carlo method.

Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
Baseline (screening) and Month 12

The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

Part A: Change From Baseline in Proteinuria at Week 48
Baseline (Day 1) and Week 48

Change from baseline in proteinuria was assessed based on urinary protein-to-creatinine ratio (uPCR). Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug.

Part B: Change From Baseline in Proteinuria at Week 168
Baseline (Part A, Week 48) and Week 168

Change from baseline in proteinuria was assessed based on uPCR. Baseline was defined as the most recent non-missing measurement prior to or on the first administration of study drug during Part B.

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity
Part A:From first dose of study drug (Part A Day 1) up to 30days after last dose of study drug in Part A,approximately 366days Part B:From first dose of study drug (Part B Day 1) up to 56days after last dose of study drug in Part B,approximately 980days

TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 56 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were graded according to Common Terminology Criteria for Adverse Events v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.

Secondary Endpoints

Number of Subjects With an Hb Response in the Absence of Transfusions
Baseline and Week 26
Change From Baseline in Absolute Reticulocyte Count (ARC) at Week 26
Baseline and Week 26
Change From Baseline in Hb Concentration at Week 26
Baseline and Week 26
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Standard of Care (SOC) excluding complement inhibitorsNO_INTERVENTION -
1,080mg APL-2 administered subcutaneously twice weeklyEXPERIMENTAL -
APL-2 15mg 0.1 mL monthly for 24 monthsEXPERIMENTALA single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month
APL-2 15mg 0.1 mL EOM for 24 monthsEXPERIMENTALA single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month
Sham Procedure Monthly for 24 monthsEXPERIMENTALSham Procedure for 24 months
Sham Procedure Every Other Month for 24 monthsEXPERIMENTALSham Procedure every other month for 24 months
APL-2EXPERIMENTALOpen Label, Study Drug, APL-2
270mg or 360mg APL-2 administered subcutaneously daily (CAD)EXPERIMENTAL -
270mg or 360mg APL-2 administered subcutaneously daily (wAIHA)EXPERIMENTAL -

Interventions

NameTypeDescription
APL-2DRUGComplement (C3) Inhibitor
Sham ProcedureOTHERSubjects will receive a Sham procedure every month
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites30

Inclusion Criteria: * Be at least 18 years old (inclusive). * Have LDH ≥1.5 x ULN at the screening visit. * Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone \>10%). * Have Hb less than the lower limit of normal (LLN) at the screening visit. * Have ferr...

Countries:ColombiaHong KongMalaysiaMexicoPeruPhilippinesPolandSerbiaSingaporeThailandUnited StatesArgentinaAustraliaBrazilCanadaCzechiaFranceGermanyIsraelItalyNew ZealandPuerto RicoSpainUnited KingdomNetherlands
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Frequently asked questions about APL-2

What is APL-2 used for?

APL-2, also known as pegcetacoplan, is an investigational therapy being studied for paroxysmal nocturnal hemoglobinuria, geographic atrophy, warm autoimmune hemolytic anemia, and IgA nephropathy. It is in Phase 3 clinical development for these conditions.

What does APL-2 target?

APL-2 targets the complement system. It is designed to inhibit complement component C3, which plays a role in the immune response. This mechanism is being investigated for conditions like geographic atrophy and paroxysmal nocturnal hemoglobinuria.

Who makes APL-2?

APL-2 is being developed by Apellis Pharmaceuticals, Inc., a biopharmaceutical company. The company's stock is traded under the ticker symbol APLS.

What phase is APL-2 in?

APL-2 is in Phase 3 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Clinical trials are ongoing to evaluate its safety and efficacy for various indications.

What clinical trials is APL-2 in?

APL-2 has been studied in several Phase 3 trials. These include NCT03525600 and NCT03525613 for geographic atrophy secondary to age-related macular degeneration, NCT04085601 for paroxysmal nocturnal hemoglobinuria, and NCT07214740 for geographic atrophy using a prefilled syringe.

Is APL-2 the same as pegcetacoplan?

Yes, APL-2 is also known as pegcetacoplan. The drug is referred to by both names in clinical research and development contexts.