Safely Quenching Complement in Stroke Survivors (SUCCESS)

April 24, 2026 updated by: E. Sander Connolly, Columbia University

Safely Quenching Complement in Stroke Subjects: A Phase 1 Safety Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Acute ischemic stroke (AIS) remains the primary cause of disability worldwide. Advances in revascularization therapies such as pharmacologic thrombolysis and intra-arterial endovascular thrombectomy (EVT) have improved outcomes, yet >50% of patients remain functionally disabled at 90 days post-ictus onset despite high recanalization rates. One major reason for this limited recovery is the activation of thrombo-inflammatory processes beyond the initial vessel occlusion. These processes contribute to reperfusion injury and secondary brain damage, which current standard-of-care treatments fail to address. EMPAVELI (Pegcetacoplan) is a targeted C3 inhibitor developed by Apellis Pharmaceuticals. It is FDA-approved for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) and has demonstrated effective inhibition of complement-mediated inflammation. By selectively inhibiting C3, EMPAVELI prevents excessive complement activation while preserving key immune functions, making it an attractive candidate for neuroprotection in AIS patients.

This is a prospective, single-center, open-label, single-arm, interventional clinical trial. It is designed to assess the safety and tolerability of a single subcutaneous dose of the complement C3 inhibitor EMPAVELI (pegcetacoplan) in adult patients with AIS due to anterior circulation LVO who have undergone successful or near-complete EVT. The study is classified as a Phase 1experimental trial with a primary focus on safety. There is no randomization, no control group, and no blinding. The design is non-randomized and non-comparative, using historical controls for contextual reference only. All enrolled subjects will receive the same intervention: three subcutaneous injections of EMPAVELI (1,080 mg) administered within 3 hours post-reperfusion and at 24 and 48 hours after the initial dose, aligning with the acute thrombo-inflammatory phase of stroke recovery.

The study involves serial clinical and laboratory assessments over a 90-day period, including pharmacokinetic (PK), pharmacodynamic (PD), and clinical outcome measurements (e.g., NIHSS, mRS, GCS, Barthel Index). Safety assessments will include adverse event (AE) monitoring, laboratory studies (CBC, BMP, liver function tests), vital signs, and imaging. Imaging includes MRIs and TCDs, both in the standard of care at CUIMC. Follow-up evaluations will be conducted in person (up to 72 hours or hospital discharge) and via telephone at Days 30 and 90.

The study does not involve any ethnographic or qualitative methodology and is not observational in nature. Its primary purpose is to generate foundational safety data to inform future randomized controlled trials assessing the efficacy of EMPAVELI in AIS patients.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Episode of fever > 38.5 degrees Celsius during admission and prior to enrollment.
  • History of any clinically significant disease or disorder which, in the opinion of the Investigator, could have either put the subject at risk because of participation in the study, or interfered with interpretation of the subject's study results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Empaveli (Pegcetacoplan) Treatment
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]
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.
Other Names:
  • APL-2
  • Empaveli

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events
Time Frame: Through 90 days post-treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological Functional Outcome
Time Frame: Through 90 days post-treatment
Functional outcome as measured by the modified Rankin Scale (mRS). The scale is from 0-6, where 0 indicates no symptoms at all and 6 indicates Death. Therefore, higher scores represent worse outcomes.
Through 90 days post-treatment
Neurological Deficit Severity
Time Frame: Baseline through 90 days
Change in National Institutes of Health Stroke Scale (NIHSS) score from baseline. The scale is graded from 0-42, with a score of 0 indicating no stroke while a maximum score of 42 indicates severe stroke. A higher score represents greater stroke severity.
Baseline through 90 days
Biomarker Response
Time Frame: Baseline through 90 days
Changes in complement and neuroinjury biomarkers (e.g., C3, C3b, S100b, GFAP)
Baseline through 90 days
Maximum Plasma Concentration [Cmax] of Pegcetacoplan
Time Frame: Through 72 hours
Maximum observed plasma concentration (Cmax) of pegcetacoplan following administration.
Through 72 hours
Time to Maximum Plasma Concentration [Tmax] of Pegcetacoplan
Time Frame: Through 72 hours.
Time to reach maximum observed plasma concentration (Tmax) of pegcetacoplan.
Through 72 hours.
Infectious Complications
Time Frame: During hospitalization and through 90 days
Incidence of infections including sepsis, pneumonia, and urinary tract infections
During hospitalization and through 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Investigators

  • Principal Investigator: E Sander Connolly, MD, Columbia University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

March 18, 2026

First Submitted That Met QC Criteria

March 24, 2026

First Posted (Actual)

March 27, 2026

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 24, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAV9617

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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