Safely Quenching Complement in Stroke Survivors

NCT07495722 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: AAAV9617
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will include adults (ages 18-80) who have had a stroke caused by a large blood clot blocking blood flow in the brain. All patients in the study must have already had a treatment called a thrombectomy, where doctors remove the clot to help blood flow return to the brain. The goal of this study is to test the safety of a drug called EMPAVELI (pegcetacoplan). This drug is meant to lower swelling and inflammation that can happen after blood flow returns. The hope is that it may help protect the brain from more damage and improve recovery. People in the study will get three doses of EMPAVELI through an EMPAVELI-designed pump 0-3 hours post thrombectomy surgery and 24 and 48 hours after the initial dose. Doctors will check them with exams, blood tests, brain scans, and other tests while they are there. Patients will also have follow-up visits at 30 and 90 days to see how they are doing, per the usual standard of care. This research is important because, even with current stroke treatments, many patients still have problems like disability. If this drug is found to be safe, it could lead to better treatments to protect the brain and help people recover more fully after a stroke.

Conditions

Acute Ischemic Stroke; Cerebral Infarction

Keywords

endovascular thrombectomy; large vessel occlusion; reperfusion injury; complement inhibition; C3 inhibition; pegcetacoplan; empaveli; neuroprotection; thromboinflammation; stroke recovery

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  To evaluate the safety and tolerability of pegcetacoplan (Empaveli) in adult patients with acute ischemic stroke following endovascular thrombectomy, as measured by the incidence, type, and severity of treatment-emergent adverse events (AEs) and serious adverse events (SAEs).

  Through 90 days post-treatment

Secondary Outcomes (6)

• Neurological Functional Outcome

  Through 90 days post-treatment

• Neurological Deficit Severity

  Baseline through 90 days

• Biomarker Response

  Baseline through 90 days

• Maximum Plasma Concentration [Cmax] of Pegcetacoplan

  Through 72 hours

• Time to Maximum Plasma Concentration [Tmax] of Pegcetacoplan

  Through 72 hours.

Study Arms (1)

Empaveli (Pegcetacoplan) Treatment

EXPERIMENTAL

Participants will receive pegcetacoplan (Empaveli) administered as three subcutaneous doses of 1,080 mg given within 0-3 hours following endovascular thrombectomy, and at 24 and 48 hours after the initial dose. This is a single-arm, open-label study designed to evaluate the safety and tolerability of complement C3 inhibition in adults with acute ischemic stroke due to anterior circulation large vessel occlusion.

Drug: Pegcetacoplan Injection [Empaveli]

Interventions

Pegcetacoplan Injection [Empaveli] DRUG

In this study, participants will receive three 1,080 mg doses delivered within 0-3 hours following endovascular thrombectomy, and at 24 and 48 hours after the initial dose. Pegcetacoplan is FDA-approved for the treatment of paroxysmal nocturnal hemoglobinuria and is being evaluated in this study for its safety and tolerability in acute ischemic stroke patients following reperfusion.

Also known as: Empaveli, APL-2

Empaveli (Pegcetacoplan) Treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (18-80 years old)
• Diagnosis of AIS due to anterior circulation (Intracranial ICA, M1 MCA) LVO with evidence of complete/near-complete revascularization following EVT (mTICI ≥2b).
• Enrollment within 24 hours of reperfusion, with reperfusion occurring within 24 hours of ictus onset.
• Body weight ≥ 50 kg.
• Absolute reticulocyte count \>1.0 x ULN
• Platelet count of \>50,000/mm³
• Absolute neutrophil count (ANC) ≥ 1500/mm³ at
• Vaccination against Neisseria meningitidis types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day1 dosing, or within 14 days after EMPAVELI. Unless documented evidence exists, that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after study drug administration.
• Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after study drug administration.
• English/Spanish-speaking patients or legally authorized representatives (LARs).
• Signed informed consent from the patient or LAR.

You may not qualify if:

• Pregnant or lactating female
• Suspected pregnancy.
• Renal insufficiency (GFR\<30mL/minute OR creatinine \>2 mg/dL OR need for renal replacement therapy (RRT) at time of admission).
• Platelet count \< 50,000/mm³
• Absolute neutrophil count \<1500/mm³
• Baseline mRS \>2
• Presence of concomitant serious illness that would confound study, including but not limited to serious psychiatric or autoimmune disease, sepsis, or trauma.
• Immunocompromised status (e.g., subjects with Human Immunodeficiency Virus \[HIV\] infection, neutropenia, complement deficiency, etc.)
• Autoimmune disorder (Sjogren's Disease, Psoriasis, hediak-Higashi Syndrome)
• Presence of any intracranial bleed (ICH, SAH, SDH, hemorrhagic lesion).
• Active hepatic failure as defined by AST \>160 units/L and/or ALT \>180 units/L, or total bilirubin levels greater than four times normal levels (\>4.8mg/dL).
• Continued use of digoxin or amlodipine (as recommended by the manufacturer due to CYP3A inhibition).
• Patients with DNR orders.
• Known infection at the time of admission (elevated WBC with identified infection source)
• Evidence of blood dyscrasia.

Sponsors & Collaborators

• Columbia University: lead

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Infarction; Reperfusion Injury; Thromboinflammation

Interventions

pegcetacoplan

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Postoperative Complications; Thrombosis; Embolism and Thrombosis; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Inflammation

Study Officials

• E Sander Connolly, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela Velazquez

CONTACT

6465151909; agv2113@cumc.columbia.edu

Eleonora F Spinazzi, MD

CONTACT

efs2110@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair and Professor, Department of Neurological Surgery

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: March 27, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share