Cerebral Edema, Intracerebral Hemorrhage, Intracerebral Hemorrhage, Hypertensive, Intracerebral Hemorrhage Intraparenchymal, Stroke Hemorrhagic
Conditions
Keywords
Fingolimod, Neurologic Deficits, Brain Injury, Stroke, Intracerebral hemorrhage, Neuroimmunomodulation
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).
Detailed description
This is a double-blinded, placebo-controlled pilot trial of fingolimod in patients with primary spontaneous intracerebral hemorrhage. Eligible participants will be allocated to study groups using fixed allocation randomization and a computer-based random number-generating allocation. For those patients who meet all inclusion criteria without exclusion criteria subjects will receive oral or nasogastric tube (NGT) or Dobhoff feeding tube administration of fingolimod versus placebo. Participants will be monitored at time of enrollment and days 1, 3 5, 7, and 14 (discharge dependent) by 2 blinded assessors (neuroscience subspecialists) and will receive standard of care for the duration of the study. After discharge from the hospital, participants will enter a follow up phase of 12 months, with clinic visits at 30±14 days, 90±14 days, 180±14 days, and 365±14 days. They will receive a standard of care neuroimaging at these follow up time-points and will be assessed with the pre-selected outcome assessments established by the NINDS Common Data Elements for Stroke.
Interventions
DRUGFingolimod
A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset
DRUGPlacebo
A single oral placebo pill within 24 hours of symptom onset
DRUGOpen-label Fingolimod
A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Randomized, double-blinded, placebo-controlled pilot trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
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. Men and non-pregnant women ages 18-80 years old Has a confirmed diagnosis of spontaneous supratentorial ICH. The presence of cerebellar ICH is exclusionary. Presence of hydrocephalus due to mass effect and cerebral edema is not exclusionary. If the patient has hydrocephalus requiring CSF drainage, an external ventricular drain will be placed as standard of care and will not be exclusionary. Symptoms less than 24 hours prior to enrollment if all eligibility criteria are met. An unknown time of onset is exclusionary. Use the time the patient was last known to be well for patients that awaken from sleep with symptoms. 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.
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Cardiac Events | up to 30 days post-ictus | 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. |
| Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia) | up to 90 days post-ictus | Rate of nosocomial infections (UTI, sepsis, and pneumonia) by group |
| Rate of Neurologic Decline | up to 30 days post-ictus | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Lymphocyte Subpopulations of CD19+ B Cells | Enrollment and 30 days | Percent change in lymphocyte subpopulations of CD19+ B cells |
| Change in Hematoma Volume Obtained by MRI | Enrollment and 365 days | Average decrease per day by group in volumetric measurement calculations of hematoma obtained by MRI between enrollment and 365 days. All MRI imaging data obtained on hematoma volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject. |
| Change in Hematoma Volume Obtained by CT | Enrollment and 365 days | Average decrease per day by group in volumetric measurement calculations of hematoma obtained by CT between enrollment and 365 days. All CT imaging data obtained on hematoma volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject. |
| Change in Peri-hematomal Edema Volume Obtained by CT | Enrollment to 365 days | Average decrease per day by group in volumetric measurement calculations of peri-hematomal edema volume between enrollment and 365 days. All CT imaging data obtained on peri-hematomal edema volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject. |
| Change in Peri-hematomal Edema Volume Obtained by MRI | Enrollment to 365 days | Average decrease per day by group in volumetric measurement calculations of peri-hematomal edema obtained from radiographic imaging (MRI) between enrollment and 365 days. All MRI imaging data obtained on peri-hematomal edema volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject. |
| National Institutes of Health Stroke Scale Total Score (NIHSS) | 365 days | The scoring range is 0 to 42 points, with higher numbers indicating greater severity. (NIHSS) |
| Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube | Enrollment | Rate of successful administration of fingolimod through an NGT or Dobhoff tube in Open-label group only |
| Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | 365 days | Patient-Reported Outcomes Measurement Information System (PROMIS) 10 questionnaire will measure patient self-reporting of physical and neurobehavioral functions. Mean T-score for general population is 50 with standard deviation of 10. Higher T-scores indicate better physical and mental health. Typically, T-score ranges from 20 to 80. |
| Montreal Cognitive Assessment (MoCA) | 365 days | Montreal Cognitive Assessment (MoCA) will measure recovery (neurocognitive). Scores range from 0 to 30 with higher scores denoting better outcomes. |
| Western Aphasia Battery-Revised (WAB-R) | 365 days | Western Aphasia Battery-Revised (WAB-R) will measure recovery (neurocognitive and speech). Language and Aphasia subscale scores both range from 0 to 100. Higher scores denote better outcome. |
| Mortality | 30 days | Mortality at 30 days |
| All Cause Mortality | up to 365 days | All cause mortality within 365 days |
| Interviewer-administered Modified Rankin Scale (mRS) | 365 days post-ictus | The modified Rankin Scale (mRS) will measure functional recovery and ability to perform activities of daily living. The mRS is a 6 point disability scale with scores ranging from 0 (no symptoms) to 5 (severe disability) with 6 indicating death. Lower scores denote better outcome. |
| Percent Change in Lymphocyte Subpopulations of CD4+ T Cells | Enrollment to 30 days | Percent Change in Lymphocyte Subpopulations of CD4+ T Cells |
| Percent Change in Lymphocyte Subpopulations of CD8+ T Cells | Enrollment and 30 days | Percent change in lymphocyte subpopulations of CD8+ T Cells |
Countries
United States
Participant flow
Recruitment details
Adult patients coming the Emergency Department or direct admitted to the Neurosciences Intensive Care Unit at Wake Forest Baptist Hospital between August 2020 and June 2023 with the diagnosis of spontaneous ICH will be identified as potentially eligible participants and screened by interview.
Pre-assignment 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.
Participants by arm
| Arm | Count |
|---|---|
| Fingolimod 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.
Fingolimod: A single dose of 0.5 mg oral fingolimod within 24 hours of symptom onset | 9 |
| Control 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
Control: A single oral placebo pill within 24 hours of symptom onset | 8 |
| Open-label Fingolimod In addition to standard of care treatment,10 subjects 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.
Open-label Fingolimod: A single dose of 0.5 mg fingolimod through an NGT or Dobhoff tube within 24 hours of symptom onset | 11 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 1 |
| Overall Study | Lost to Follow-up | 3 | 2 | 6 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Fingolimod | Control | Open-label Fingolimod | Total |
|---|---|---|---|---|
| Age, Continuous | 71.0 years | 67.0 years | 59.0 years | 66.0 years |
| Anticoagulant Medication | 4 Participants | 2 Participants | 0 Participants | 6 Participants |
| Antiplatelet medication | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Atrial Fibrillation | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Coronary Artery Disease | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Diabetes | 2 Participants | 0 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 6 Participants | 7 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hyperlipidemia | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Hypertension | 5 Participants | 8 Participants | 8 Participants | 21 Participants |
| Obesity | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Prior stroke | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 5 Participants | 18 Participants |
| Smoking Status Current or Former | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Smoking Status Never | 4 Participants | 1 Participants | 5 Participants | 10 Participants |
| Smoking Status Unknown | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 9 | 1 / 8 | 1 / 11 |
| other Total, other adverse events | 0 / 9 | 0 / 8 | 0 / 11 |
| serious Total, serious adverse events | 3 / 9 | 1 / 8 | 5 / 11 |
Outcome results
Primary
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.
Time frame: up to 30 days post-ictus
Population: All enrolled participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Number of Participants With Clinically Significant Cardiac Events | 3 Participants |
| Control | Number of Participants With Clinically Significant Cardiac Events | 0 Participants |
| Open-label Fingolimod | Number of Participants With Clinically Significant Cardiac Events | 0 Participants |
Comparison: Difference in proportion of subjects with cardiac events up to 30 days post-ictus tested between three groups.p-value: 0.0427Fisher Exact
Primary
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.
Time frame: up to 30 days post-ictus
Population: All three arms where data were available at 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Rate of Neurologic Decline | 2 Participants |
| Control | Rate of Neurologic Decline | 0 Participants |
| Open-label Fingolimod | Rate of Neurologic Decline | 0 Participants |
Comparison: Difference in proportion of subjects with neurologic decline up to 30 days post-ictus tested between three groups. No pairwise comparisons performed.p-value: 0.3Fisher Exact
Primary
Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia)
Rate of nosocomial infections (UTI, sepsis, and pneumonia) by group
Time frame: up to 90 days post-ictus
Population: All enrolled participants by group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia) | 1 Participants |
| Control | Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia) | 1 Participants |
| Open-label Fingolimod | Rate of Nosocomial Infections (UTI, Sepsis, and Pneumonia) | 5 Participants |
Comparison: Difference in proportion of subjects with nosocomial infections up to 90 days post-ictus tested between three groups. No pairwise comparisons performed.p-value: 0.19Fisher Exact
Secondary
All Cause Mortality
All cause mortality within 365 days
Time frame: up to 365 days
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | All Cause Mortality | 3 Participants |
| Control | All Cause Mortality | 1 Participants |
| Open-label Fingolimod | All Cause Mortality | 1 Participants |
Secondary
Change in Hematoma Volume Obtained by CT
Average decrease per day by group in volumetric measurement calculations of hematoma obtained by CT between enrollment and 365 days. All CT imaging data obtained on hematoma volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject.
Time frame: Enrollment and 365 days
Population: All enrolled subjects included in analysis. Fingolimod group included 46 observations, placebo included 39 observations and open-label included 60 observations across the time period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod | Change in Hematoma Volume Obtained by CT | -156.84 mm^3 per day | Standard Error 46.35 |
| Control | Change in Hematoma Volume Obtained by CT | -90.56 mm^3 per day | Standard Error 54.89 |
| Open-label Fingolimod | Change in Hematoma Volume Obtained by CT | -86.73 mm^3 per day | Standard Error 15.95 |
Secondary
Change in Hematoma Volume Obtained by MRI
Average decrease per day by group in volumetric measurement calculations of hematoma obtained by MRI between enrollment and 365 days. All MRI imaging data obtained on hematoma volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject.
Time frame: Enrollment and 365 days
Population: All enrolled subjects included in analysis. Fingolimod group included 18 observations, placebo included 14 observations and open-label included 23 observations across the time period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod | Change in Hematoma Volume Obtained by MRI | -247.19 mm^3 per day | Standard Error 75.68 |
| Control | Change in Hematoma Volume Obtained by MRI | -86.29 mm^3 per day | Standard Error 17.74 |
| Open-label Fingolimod | Change in Hematoma Volume Obtained by MRI | -210.03 mm^3 per day | Standard Error 23.81 |
Secondary
Change in Peri-hematomal Edema Volume Obtained by CT
Average decrease per day by group in volumetric measurement calculations of peri-hematomal edema volume between enrollment and 365 days. All CT imaging data obtained on peri-hematomal edema volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject.
Time frame: Enrollment to 365 days
Population: All enrolled subjects included in analysis. Fingolimod group included 46 observations, placebo included 39 observations and open-label included 60 observations across the time period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod | Change in Peri-hematomal Edema Volume Obtained by CT | -65.85 mm^3 | Standard Error 47.5 |
| Control | Change in Peri-hematomal Edema Volume Obtained by CT | -62.21 mm^3 | Standard Error 64.76 |
| Open-label Fingolimod | Change in Peri-hematomal Edema Volume Obtained by CT | -64.93 mm^3 | Standard Error 16.33 |
Secondary
Change in Peri-hematomal Edema Volume Obtained by MRI
Average decrease per day by group in volumetric measurement calculations of peri-hematomal edema obtained from radiographic imaging (MRI) between enrollment and 365 days. All MRI imaging data obtained on peri-hematomal edema volume between enrollment and 365 days were used to calculate estimates via a linear mixed effects model controlling for repeated measures within subject.
Time frame: Enrollment to 365 days
Population: All enrolled subjects included in analysis. Fingolimod group included 18 observations, placebo included 14 observations and open-label included 23 observations across the time period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod | Change in Peri-hematomal Edema Volume Obtained by MRI | -327.12 mm^3 | Standard Error 89.61 |
| Control | Change in Peri-hematomal Edema Volume Obtained by MRI | -118.36 mm^3 | Standard Error 31.75 |
| Open-label Fingolimod | Change in Peri-hematomal Edema Volume Obtained by MRI | -74.96 mm^3 | Standard Error 55.84 |
Secondary
Interviewer-administered Modified Rankin Scale (mRS)
The modified Rankin Scale (mRS) will measure functional recovery and ability to perform activities of daily living. The mRS is a 6 point disability scale with scores ranging from 0 (no symptoms) to 5 (severe disability) with 6 indicating death. Lower scores denote better outcome.
Time frame: 365 days post-ictus
Population: Subjects where scores were collected at 365 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | Interviewer-administered Modified Rankin Scale (mRS) | 1.5 score on a scale |
| Control | Interviewer-administered Modified Rankin Scale (mRS) | 1.5 score on a scale |
| Open-label Fingolimod | Interviewer-administered Modified Rankin Scale (mRS) | 2.5 score on a scale |
Secondary
Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA) will measure recovery (neurocognitive). Scores range from 0 to 30 with higher scores denoting better outcomes.
Time frame: 365 days
Population: Subjects completing instrument at 365 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | Montreal Cognitive Assessment (MoCA) | 25 score on a scale |
| Control | Montreal Cognitive Assessment (MoCA) | 24 score on a scale |
| Open-label Fingolimod | Montreal Cognitive Assessment (MoCA) | 20 score on a scale |
Secondary
Mortality
Mortality at 90 days
Time frame: 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Mortality | 1 Participants |
| Control | Mortality | 1 Participants |
| Open-label Fingolimod | Mortality | 0 Participants |
Secondary
Mortality
Mortality at 30 days
Time frame: 30 days
Population: All enrolled subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Mortality | 0 Participants |
| Control | Mortality | 1 Participants |
| Open-label Fingolimod | Mortality | 0 Participants |
Secondary
National Institutes of Health Stroke Scale Total Score (NIHSS)
The scoring range is 0 to 42 points, with higher numbers indicating greater severity. (NIHSS)
Time frame: 365 days
Population: Subjects where score was collected at 365 days.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | National Institutes of Health Stroke Scale Total Score (NIHSS) | 0 score on a scale |
| Control | National Institutes of Health Stroke Scale Total Score (NIHSS) | 1 score on a scale |
| Open-label Fingolimod | National Institutes of Health Stroke Scale Total Score (NIHSS) | 5 score on a scale |
Secondary
Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire
Patient-Reported Outcomes Measurement Information System (PROMIS) 10 questionnaire will measure patient self-reporting of physical and neurobehavioral functions. Mean T-score for general population is 50 with standard deviation of 10. Higher T-scores indicate better physical and mental health. Typically, T-score ranges from 20 to 80.
Time frame: 365 days
Population: Subjects completing instrument at 365 days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fingolimod | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Physical T Score | 48.2 score on a scale |
| Fingolimod | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Mental T Score | 53.4 score on a scale |
| Control | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Physical T Score | 55.9 score on a scale |
| Control | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Mental T Score | 47.7 score on a scale |
| Open-label Fingolimod | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Physical T Score | 47.7 score on a scale |
| Open-label Fingolimod | Patient-Reported Outcomes Measurement Information (PROMIS) 10 Questionnaire | Mental T Score | 41.1 score on a scale |
Secondary
Percent Change in Lymphocyte Subpopulations of CD19+ B Cells
Percent change in lymphocyte subpopulations of CD19+ B cells
Time frame: Enrollment and 30 days
Population: Subjects where 30 day labs were obtained are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | Percent Change in Lymphocyte Subpopulations of CD19+ B Cells | 121 percent change |
| Control | Percent Change in Lymphocyte Subpopulations of CD19+ B Cells | 0.230 percent change |
| Open-label Fingolimod | Percent Change in Lymphocyte Subpopulations of CD19+ B Cells | 9.22 percent change |
Secondary
Percent Change in Lymphocyte Subpopulations of CD4+ T Cells
Percent Change in Lymphocyte Subpopulations of CD4+ T Cells
Time frame: Enrollment to 30 days
Population: Subjects where 30 day labs were obtained are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | Percent Change in Lymphocyte Subpopulations of CD4+ T Cells | 19.6 percent change |
| Control | Percent Change in Lymphocyte Subpopulations of CD4+ T Cells | -2.56 percent change |
| Open-label Fingolimod | Percent Change in Lymphocyte Subpopulations of CD4+ T Cells | -5.00 percent change |
Secondary
Percent Change in Lymphocyte Subpopulations of CD8+ T Cells
Percent change in lymphocyte subpopulations of CD8+ T Cells
Time frame: Enrollment and 30 days
Population: Subjects where 30 day labs were obtained are included in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fingolimod | Percent Change in Lymphocyte Subpopulations of CD8+ T Cells | 19.3 percent change |
| Control | Percent Change in Lymphocyte Subpopulations of CD8+ T Cells | 21.4 percent change |
| Open-label Fingolimod | Percent Change in Lymphocyte Subpopulations of CD8+ T Cells | 21.6 percent change |
Secondary
Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube
Rate of successful administration of fingolimod through an NGT or Dobhoff tube in Open-label group only
Time frame: Enrollment
Population: 11 subjects enrolled in open-label arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fingolimod | Rate of Successful Administration of Fingolimod Through an NGT or Dobhoff Tube | 11 Participants |
Secondary
Western Aphasia Battery-Revised (WAB-R)
Western Aphasia Battery-Revised (WAB-R) will measure recovery (neurocognitive and speech). Language and Aphasia subscale scores both range from 0 to 100. Higher scores denote better outcome.
Time frame: 365 days
Population: Subjects completing instrument at 365 days.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fingolimod | Western Aphasia Battery-Revised (WAB-R) | Language score | 98.8 score on a scale |
| Fingolimod | Western Aphasia Battery-Revised (WAB-R) | Aphasia score | 100 score on a scale |
| Control | Western Aphasia Battery-Revised (WAB-R) | Language score | 96.9 score on a scale |
| Control | Western Aphasia Battery-Revised (WAB-R) | Aphasia score | 98.3 score on a scale |
| Open-label Fingolimod | Western Aphasia Battery-Revised (WAB-R) | Language score | 90.0 score on a scale |
| Open-label Fingolimod | Western Aphasia Battery-Revised (WAB-R) | Aphasia score | 95.0 score on a scale |