Acute Ischemic StrokePhase 1SUCCESSNCT07495722
Safely Quenching Complement in Stroke Survivors
A Phase 1 study testing Pegcetacoplan Injection [Empaveli] in people with Acute Ischemic Stroke and Cerebral Infarction, run by Columbia University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Ischemic Stroke, Cerebral Infarction
- What is being tested?
- Pegcetacoplan Injection [Empaveli]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Aug 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Eleonora F Spinazzi, MD contact
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Acute Ischemic Stroke, Cerebral Infarction
- Being tested
- Pegcetacoplan Injection [Empaveli]
- Keywords
- endovascular thrombectomy, large vessel occlusion, reperfusion injury, complement inhibition, C3 inhibition, pegcetacoplan, empaveli, neuroprotection, thromboinflammation, stroke recovery
- Medical subject headings
- Ischemic Stroke, Cerebral Infarction, Reperfusion Injury, Thromboinflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pegcetacoplan Injection [Empaveli]Drug
Also called Empaveli, APL-2
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pegcetacoplan Injection [Empaveli] |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through 90 days post-treatment
Secondary outcomes (6)
Neurological Functional Outcome
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.
Measured: Through 90 days post-treatment
Neurological Deficit Severity
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.
Measured: Baseline through 90 days
Biomarker Response
Changes in complement and neuroinjury biomarkers (e.g., C3, C3b, S100b, GFAP)
Measured: Baseline through 90 days
Maximum Plasma Concentration [Cmax] of Pegcetacoplan
Maximum observed plasma concentration (Cmax) of pegcetacoplan following administration.
Measured: Through 72 hours
Time to Maximum Plasma Concentration [Tmax] of Pegcetacoplan
Time to reach maximum observed plasma concentration (Tmax) of pegcetacoplan.
Measured: Through 72 hours.
Infectious Complications
Incidence of infections including sepsis, pneumonia, and urinary tract infections
Measured: During hospitalization and through 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study startOct 2026 (estimated)
- Primary completionApr 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, E. Sander Connolly, Columbia University
- Investigators
- E Sander Connolly, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07495722
- Sponsor's protocol ID
- AAAV9617
- Acronym
- SUCCESS
- Status last verified
- Apr 2026
- First submitted
- 18 Mar 2026
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safely Quenching Complement in Stroke Subjects: A Phase 1 Safety Trial
- ClinicalTrials.gov ID
- NCT07495722
- Acronym / sponsor ID
- SUCCESS / AAAV9617
- Conditions
- Acute Ischemic Stroke, Cerebral Infarction
- Keywords
- endovascular thrombectomy, large vessel occlusion, reperfusion injury, complement inhibition, C3 inhibition, pegcetacoplan, empaveli, neuroprotection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Oct 2026 (estimated)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Empaveli (Pegcetacoplan) Treatment | Experimental | Drug: Pegcetacoplan Injection [Empaveli]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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pegcetacoplan Injection [Empaveli]Also: Empaveli, APL-2In 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. | Drug | Empaveli (Pegcetacoplan) Treatment |
Primary outcome
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).
6 secondary outcomes
Neurological Functional Outcome
Time frame: Through 90 days post-treatment
Neurological Deficit Severity
Time frame: Baseline through 90 days
Biomarker Response
Time frame: Baseline through 90 days
Maximum Plasma Concentration [Cmax] of Pegcetacoplan
Time frame: Through 72 hours
Time to Maximum Plasma Concentration [Tmax] of Pegcetacoplan
Time frame: Through 72 hours.
Infectious Complications
Time frame: During hospitalization and through 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eleonora F Spinazzi, MD contact
E Sander Connolly, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pegcetacoplan Injection [Empaveli] in people with Acute Ischemic Stroke and Cerebral Infarction, run by Columbia University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Angela Velazquez (6465151909, agv2113@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: Through 90 days post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.