Ignite Creation Date:
2026-03-26 @ 3:15 PM
Ignite Modification Date:
2026-03-30 @ 2:46 AM
Study NCT ID:
NCT07388550
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-25
First Post:
2026-02-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)
Organization:
Study Overview
Official Title:
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post-Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-03-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from an acute COVID-19 infection may continue to have symptoms that persist for months or years. These can include neurological symptoms, such as headaches, loss of taste or smell, dizziness, or trouble walking. Pembrolizumab is a drug approved to treat certain cancers. Researchers think this drug might reduce long-term neurologic symptoms after a COVID-19 infection.
Objective:
To test pembrolizumab in people with ongoing neurologic symptoms of COVID-19.
Eligibility:
People aged 18 years or older who had COVID-19 at least 6 months ago and have ongoing neurologic symptoms.
Design:
Participants will have 7 clinic visits in 7 months.
Participants will be screened. They will have a physical exam with blood tests. Swabs will be used to collect cells from inside the mouth and nose. They may opt to have an imaging scan.
Participants will also have other tests before they are given the study drug. These include eye and skin exams; tests of their memory and thinking; and tests of involuntary body functions, such as heart rate, blood pressure, sweating, and digestion. Their grip strength and walking pace will be measured. They will wear a heart rate monitor for 24 hours. They will wear devices on a wrist and thigh to measure activity for 10 days.
Participants will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord.
Pembrolizumab is given through a needle inserted into a vein. Participants will receive 1 dose of the drug.
Participants will have 4 follow-up visits over 6 months. Tests may be repeated during these visits.
SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from an acute COVID-19 infection may continue to have symptoms that persist for months or years. These can include neurological symptoms, such as headaches, loss of taste or smell, dizziness, or trouble walking. Pembrolizumab is a drug approved to treat certain cancers. Researchers think this drug might reduce long-term neurologic symptoms after a COVID-19 infection.
Objective:
To test pembrolizumab in people with ongoing neurologic symptoms of COVID-19.
Eligibility:
People aged 18 years or older who had COVID-19 at least 6 months ago and have ongoing neurologic symptoms.
Design:
Participants will have 7 clinic visits in 7 months.
Participants will be screened. They will have a physical exam with blood tests. Swabs will be used to collect cells from inside the mouth and nose. They may opt to have an imaging scan.
Participants will also have other tests before they are given the study drug. These include eye and skin exams; tests of their memory and thinking; and tests of involuntary body functions, such as heart rate, blood pressure, sweating, and digestion. Their grip strength and walking pace will be measured. They will wear a heart rate monitor for 24 hours. They will wear devices on a wrist and thigh to measure activity for 10 days.
Participants will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord.
Pembrolizumab is given through a needle inserted into a vein. Participants will receive 1 dose of the drug.
Participants will have 4 follow-up visits over 6 months. Tests may be repeated during these visits.
Detailed Description:
Study Description:
Despite clinical recovery from an acute SARS-CoV-2 infection, some individuals continue to experience ongoing symptoms for months to years afterwards, with many of these symptoms being neurologic. These neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) may be related to persisting viral antigen that leads to immune exhaustion. This study will primarily evaluate the safety of one dose of intravenous Pembrolizumab therapy in neuro-PASC participants with evidence of immune exhaustion. Pembrolizumab therapy may have positive clinical and laboratory effects on participants with persistent neurological symptoms, which will be measured as secondary outcomes.
Objectives:
Primary Objective:
-To determine the safety of a single dose of intravenous Pembrolizumab in participants with neurological postacute sequalae of SARS-CoV-2 infection.
Secondary objectives:
* To determine if one dose of intravenous Pembrolizumab can normalize markers of immune exhaustion in neuro-PASC.
* To determine if one dose of intravenous Pembrolizumab can lead to clinically relevant improvement in subjective and objective measures of ability.
Exploratory objectives:
* To determine if one dose of intravenous Pembrolizumab can change measures of SARS-CoV-2 antigen.
* To determine if one dose of intravenous Pembrolizumab can change measures of cytokines.
* To determine if one dose of intravenous Pembrolizumab can lead to improvement in subjective measures of symptoms.
Endpoints:
Primary endpoint:
\- Number of adverse events and serious adverse events.
Secondary endpoints:
* Number of participants with normalization of PD-1 expression on CD8 T cells.
* Number of participants achieving a minimal clinically important difference in measures of function:
* Work Disability Functional Assessment Battery (WDFAB)
* PROMIS Global Health
* Short Form 36 (SF-36)
* PROMIS Cognitive Function
* Montreal Cognitive Assessment (MoCA)
* Incremental shuttle walk test
Exploratory endpoints:
* Detection of viral antigen
* Change in cytokine profile
* Statistically significant positive change from baseline:
* PROMIS Depression score
* PROMIS Anxiety
* PROMIS Fatigue
* PROMIS Sleep Disturbance
* WHO post COVID-19 functional scale
* Patient Post-COVID-19 Functional Status (PCFS) scale (0-4).
* Provider Post-COVID-19 Functional Status (PCFS) scale (0-4).
* FUNCAP55
* Multidimensional Fatigue Inventory (MFI)
* Pittsburgh Sleep Quality Index (PSQI)
* Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM)
* Post Exertional Malaise Visual Analogue Scale
* Patient Global Impression of Change
* Physician Global Impression of Change
* Brief tablet-based neurocognitive testing
* Near Infrared Spectroscopy of muscle
* Actigraphy
* Hand grip strength
* Holter monitoring for 24 hrs
* Orthostatic Intolerance Questionnaire/Orthostatic Intolerance Daily Activities Scale (OIQ/OIDAS)
* Dysautonomia measures in response to the QSART, Valsalva maneuver or head-up tilt table testing.
* Ophthalmology Examination
Despite clinical recovery from an acute SARS-CoV-2 infection, some individuals continue to experience ongoing symptoms for months to years afterwards, with many of these symptoms being neurologic. These neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) may be related to persisting viral antigen that leads to immune exhaustion. This study will primarily evaluate the safety of one dose of intravenous Pembrolizumab therapy in neuro-PASC participants with evidence of immune exhaustion. Pembrolizumab therapy may have positive clinical and laboratory effects on participants with persistent neurological symptoms, which will be measured as secondary outcomes.
Objectives:
Primary Objective:
-To determine the safety of a single dose of intravenous Pembrolizumab in participants with neurological postacute sequalae of SARS-CoV-2 infection.
Secondary objectives:
* To determine if one dose of intravenous Pembrolizumab can normalize markers of immune exhaustion in neuro-PASC.
* To determine if one dose of intravenous Pembrolizumab can lead to clinically relevant improvement in subjective and objective measures of ability.
Exploratory objectives:
* To determine if one dose of intravenous Pembrolizumab can change measures of SARS-CoV-2 antigen.
* To determine if one dose of intravenous Pembrolizumab can change measures of cytokines.
* To determine if one dose of intravenous Pembrolizumab can lead to improvement in subjective measures of symptoms.
Endpoints:
Primary endpoint:
\- Number of adverse events and serious adverse events.
Secondary endpoints:
* Number of participants with normalization of PD-1 expression on CD8 T cells.
* Number of participants achieving a minimal clinically important difference in measures of function:
* Work Disability Functional Assessment Battery (WDFAB)
* PROMIS Global Health
* Short Form 36 (SF-36)
* PROMIS Cognitive Function
* Montreal Cognitive Assessment (MoCA)
* Incremental shuttle walk test
Exploratory endpoints:
* Detection of viral antigen
* Change in cytokine profile
* Statistically significant positive change from baseline:
* PROMIS Depression score
* PROMIS Anxiety
* PROMIS Fatigue
* PROMIS Sleep Disturbance
* WHO post COVID-19 functional scale
* Patient Post-COVID-19 Functional Status (PCFS) scale (0-4).
* Provider Post-COVID-19 Functional Status (PCFS) scale (0-4).
* FUNCAP55
* Multidimensional Fatigue Inventory (MFI)
* Pittsburgh Sleep Quality Index (PSQI)
* Modified Depaul Symptom Questionnaire-Post Exertional Malaise (DSQ-PEM)
* Post Exertional Malaise Visual Analogue Scale
* Patient Global Impression of Change
* Physician Global Impression of Change
* Brief tablet-based neurocognitive testing
* Near Infrared Spectroscopy of muscle
* Actigraphy
* Hand grip strength
* Holter monitoring for 24 hrs
* Orthostatic Intolerance Questionnaire/Orthostatic Intolerance Daily Activities Scale (OIQ/OIDAS)
* Dysautonomia measures in response to the QSART, Valsalva maneuver or head-up tilt table testing.
* Ophthalmology Examination
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 002294-N | None | None | View |