Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)

NCT07388550 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002294002294-N
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-Acute COVID-19 Syndrome

Keywords

PASC; Long Covid; COVID; COVID-19; Postacute Sequelae of COVID

Outcome Measures

Primary Outcomes (1)

• The primary outcome of this study is to determine the safety of a single dose of intravenous Pembrolizumab in participants with neurological post-acute sequalae of SARS-CoV-2 infection.

  From screening to Day 180.

Secondary Outcomes (2)

• To determine if one dose of intravenous Pembrolizumab can lead to clinically relevant improvement in subjective and objective measures of ability.

  Comparison between baseline, day 30, day 60 , and day 180 visits.

• To determine if one dose of intravenous Pembrolizumab can normalize markers of immune exhaustion in neuro-PASC.

  Comparison between baseline, day 30, day 60 , and day 180 visits.

Study Arms (1)

Open Label

EXPERIMENTAL

Single dose of Pembrolizumab 200 mg IV

Drug: Keytruda

Interventions

Keytruda DRUG

Single dose of Pembrolizumab 200 mg IV

Open Label

Eligibility Criteria

• Age: 18 Years - 110 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged at least 18 or older.
• Provides documentation of at least one positive COVID-19 Test. Approved test can include the following:
• PCR, NAA, or other EUA Approved test to confirm active COVID infection.
• A positive anti-nucleocapsid antibody test.
• A positive home Antigen test is acceptable when documentation of a photograph of the test with a phone-based date and time stamp is provided.
• A positive anti-Spike antibody test is accepted in unvaccinated individuals or those who had antibody testing prior to vaccination.
• Previously diagnosed with mild-moderate COVID-19 (WHO Clinical Progression Scale between 2-5. Participants who had severe acute COVID-19 requiring hospitalization or ICU care are excluded.
• If participants had multiple SARS-CoV-2 infections, they would need to be at least 6 months after the last infection.
• All participants would need to have a negative SARS-CoV-2 nasal swab at the time of enrollment. Documentation of the SARS-CoV-2 infection that led to development of PASC confirmed either by a positive testing by a commercial laboratory or a positive home test followed by confirmatory nucleocapsid antibody testing.
• Exhibiting persistent neurologic symptoms evidenced by a self-reported illness narrative of the development of persistent PASC symptoms after recovering from a SARS-CoV-2 infection. These include symptoms such as fatigue, cognitive difficulties, sleep disturbances, orthostatic intolerance, and any ongoing issues with gait instability, vision, speech, swallowing, sensation, or strength. Symptoms must persist for at least 6 months after the diagnosis of acute COVID-19.
• All participants will have PD-1 expression on CD8 T cells that is one SD above the mean value of normal controls as established in the SINS Lab and published previously.
• Moderate to severe PASC symptom severity, as determined using PCFS (minimal score of 3).
• Ability of participant to understand and sign a written informed consent document.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• For participants who have not completed a brain MRI since onset of symptoms: inability to complete brain MRI with gadolinium including contraindicated metal in the body, prior allergic reaction to gadolinium, eGFR \<45 mmol/L, or claustrophobia that is unable to be adequately treated with a low dose oral benzodiazepine.
• Contraindication to a research lumbar puncture, including use of anticoagulant medication, platelets \< 50,000/uL, PT or PTT \>1.5 x ULN for the NIH Clinical Center, if risk of lumbar puncture is increased for other reasons such as space occupying lesion, skin infection at site of the puncture or otherwise inability to complete the procedure.
• A condition that would significantly confound interpretation of the clinical and research tests as determined by the study investigators. This could include traumatic brain injury, substance use disorder, active malignancy, systemic immunologic disorders, current or previous long-term immune suppressive therapy.
• Any premorbid medical condition that would potentially cause fatigue and exercise intolerance. This includes many chronic medical diseases, such as congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe arthritis, uncontrolled asthma, renal failure, fibromyalgia, and ME/CFS.
• Symptom severity that makes it impossible for the participant to travel to NIH.
• Received a SARS-CoV-2 vaccine dose within less than 4 weeks of enrollment or is planning for any additional vaccines during the study.
• Prior treatment for PASC with immunomodulatory therapies such as check point inhibitors which in the opinion of the investigators could impact the outcome of this study.
• Current medications include oral steroids or other immunosuppressive medications which in the opinion of the investigators could impact the outcome of this study.
• Active participation in a clinical protocol which includes any intervention that may affect the results of the current study.
• Abnormal anti-thyroid panel (anti-TPO and anti-TG) test at screening visit.
• ANA titer of 1:80 or greater, positive anti-CCP.
• Aspartate aminotransferase and alanine aminotransferase values \>2x upper limit of normal precluding the use of acetaminophen
• Fasting triglyceride \> 300 mg/dL.
• Total bilirubin \>2x upper limit of normal (unless participant has Gilbert syndrome)

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; COVID-19

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Avindra Nath, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ladifatou N Fouanta, R.N.

CONTACT

(301) 529-6340; ladifatou.fouanta@nih.gov

Avindra Nath, M.D.

CONTACT

(301) 496-1561; natha@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2026
• First Posted: February 5, 2026
• Study Start (Estimated): April 21, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-03-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication.
• Access Criteria: Request for data access will need to adhere to the standard processes per each repository. These repositories allow for querying and access to shared datasets.

Locations

US (1)