Fingolimod as a Treatment of Cerebral Edema After Intracerebral Hemorrhage

NCT04088630 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: IRB00060619UL1TR001420
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and effectiveness of a single dose of fingolimod in patients with primary spontaneous intracerebral hemorrhage (ICH).

Conditions

Intracerebral Hemorrhage; Cerebral Edema; Stroke Hemorrhagic; Intracerebral Hemorrhage, Hypertensive; Intracerebral Hemorrhage Intraparenchymal

Keywords

Fingolimod; Neurologic Deficits; Brain Injury; Stroke; Intracerebral hemorrhage; Neuroimmunomodulation

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Clinically Significant Cardiac Events

  Number of participants with clinically significant cardiac events. Clinically significant cardiac events include myocardial infarction, unstable angina, stroke, transient ischemic attack, any heart failure, bradycardia and heart block. Cardiac events were monitored with telemetry up to and after 72 hours while hospitalized. A check in was performed at 30 days with an in-person clinical or hospital visit to ascertain any cardiac events via patient discussion and medical record review.

  up to 30 days post-ictus

• Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia)

  Rate of nosocomial infections (UTI, sepsis, and pneumonia) by group

  up to 90 days post-ictus

• Rate of Neurologic Decline

  considered a change ≥ 4 points of the NIHSS between enrollment and 30 days post-ictus. A higher score indicates higher severity and poorer prognosis. Scale is 0-42.

  up to 30 days post-ictus

Secondary Outcomes (16)

• Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube

  Enrollment

• Percent Change in Lymphocyte Subpopulations of CD4+ T Cells

  Enrollment to 30 days

• Percent Change in Lymphocyte Subpopulations of CD8+ T Cells

  Enrollment and 30 days

• Percent Change in Lymphocyte Subpopulations of CD19+ B Cells

  Enrollment and 30 days

• Change in Hematoma Volume Obtained by MRI

  Enrollment and 365 days

Study Arms (3)

Fingolimod

EXPERIMENTAL

In addition to Standard of care treatment, those participants randomized to the fingolimod group will receive a single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset.

Drug: Fingolimod

Placebo Control

PLACEBO COMPARATOR

In addition to Standard of care treatment, those participants randomized to the control group will receive a single dose placebo pill within 24 hours of symptom onset

Drug: Placebo

Open-label Fingolimod

EXPERIMENTAL

In addition to standard of care treatment,10 subjects who are unable to be administered oral medication will be assigned to the open-label group who will receive a single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset to assess feasibility of administration through NGT or Dobhoff tube.

Drug: Open-label Fingolimod

Interventions

Fingolimod DRUG

A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset

Fingolimod

Placebo DRUG

A single oral placebo pill within 24 hours of symptom onset

Placebo Control

Open-label Fingolimod DRUG

A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset

Open-label Fingolimod

Eligibility Criteria

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

You may qualify if:

• Has given written informed consent to participate in the study in accordance with required regulations; if a participant is not capable of providing informed consent, written consent must be obtained from the participant's legally authorized representative (LAR). When the LAR is not available for consent, Docusign for econsent may be obtained.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Has a GCS score ≥ 5 on presentation. Has a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 on presentation.
• Maintenance of SBP \< 200 mmHg at the time of enrollment and randomization. Historical Modified Rankin Scale score of 0-2.

You may not qualify if:

• Men or women \< 18 years old Incarcerated patients ICH known as a result of trauma. Primary intraventricular hemorrhage without significant intraparenchymal component.
• Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, hemorrhagic conversion of an ischemic infarct, recurrence of recent (\< 1 year) hemorrhage, neoplasms diagnosed with radiographic imaging.
• Patients with unstable mass or evolving intracranial compartment syndrome. Brainstem hemorrhage or irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing), GCS ≤ 4.
• Platelet count \< 100,000; INR \> 1.4. Any irreversible coagulopathy or known clotting disorder. Known history of Mobitz Type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome.
• Admission within the past 6 months for the following: myocardial infarction, unstable angina, stroke, decompensated heart failure requiring hospitalization, or Class III/IV heart failure.
• Baseline QTc interval ≥500 ms. Current treatment with Class Ia or Class III anti-arrhythmic drugs. Implanted cardiac devices that are not compatible with the desired MRI sequences needed for the study (non-contrast T1, T2, SWI/GRE, and FLAIR sequences).
• Abnormal liver function or liver failure. Active acute infection that is deemed by the Principal Investigator to be clinically significant.
• Chronic viral or fungal infection. Active use of antineoplastic, immunosuppressive, or immunomodulating therapies. Leukopenia with a WBC \< 2.0 x 109/L. Not expected to survive to the 365 day visit due to co-morbidities or is DNR/DNI status prior to randomization.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Concomitant enrollment in another interventional study. Inability or unwillingness of participant or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (85)

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Related Links

• Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III
• MIND: Artemis in the Removal of Intracerebral Hemorrhage
• ENRICH: Early MiNimally-invasive Removal of IntraCerebral Hemorrhage (ICH)

MeSH Terms

Conditions

Cerebral Hemorrhage; Brain Edema; Hemorrhagic Stroke; Intracranial Hemorrhage, Hypertensive; Neurologic Manifestations; Brain Injuries; Stroke

Interventions

Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines

Results Point of Contact

• Title: Carol Kittel, Senior Biostatistician
• Organization: Wake Forest University School of Medicine

c.kittel@wakehealth.edu

336-399-3832

Study Officials

• Stacey Q Wolfe, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Consented participants who can be administered an oral drug will be allocated to Fingolimod or Placebo study groups using a computer-based random number-generating allocation. Consented participants who are unable to be administered the oral drug or placebo are assigned to the open-label group. The study pharmacist will be the only member of the study to be unblinded to oral fingolimod or placebo randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blinded, placebo-controlled pilot trial.

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: August 7, 2020
• Primary Completion: June 30, 2023
• Study Completion: June 5, 2024
• Last Updated: January 23, 2025
• Results First Posted: January 14, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)