Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
Primary Purpose
HAM/TSP
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Teriflunomide
Sponsored by
About this trial
This is an interventional treatment trial for HAM/TSP focused on measuring Aubagio, Single center, Open Label
Eligibility Criteria
- INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- 18 years or older
- Diagnosis of HAM/TSP as defined by WHO criteria, including a positive HTLV-1 EIA and confirmatory Western Blot.
- Enrolled in 98-N-0047
- Patient must be willing and able to comply with all the aspects of trial design and follow-up.
- Negative QuantiFERON-TB gold, or completion of latent tuberculosis infection treatment, per CDC and National TB Controllers Association recommendations
- Ability to take oral medication and be willing to adhere to the protocol regimen
- Patients must be able to provide informed consent
- If able to become pregnant or to father a child, patient must agree to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy) for the duration of the treatment arm of the study and for two years following cessation of treatment with teriflunomide.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- Alternative diagnoses that can explain neurological disability
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with participation for the full duration of the trial; or not in the best interest of the subject to participate, in the opinion of the treating investigator
- Severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections.
- Liver dysfunction, as indicated by baseline aspartate aminotransferase (AST) or alanine or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
- Positive serological evidence of HIV, HTLV II, Hepatitis B or C
- Treatment with immunomodulatory/immunosuppressive therapy (aside from topical steroids) in the preceding 6 months.
- Pregnant or lactating women.
- Treatment with other investigational drugs within 6 months before enrollment
- Known hypersensitivity to teriflunomide or leflunomide
- Concomitant treatment with leflunomide
Sites / Locations
- National Institutes of Health Clinical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Teriflunomide
Arm Description
Teriflunomide 14 mg daily
Outcomes
Primary Outcome Measures
ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide
ex vivo spontaneous lymphoproliferation of HAM/TSP patients receiving teriflunomide and multicolor flow cytometric analysis of immune activation markers in both PBMCs and CSF
Secondary Outcome Measures
Tabulation of adverse events
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of disease laboratory and clinical measures.
Percent change between CD8+ and CD4+ cells in the CSF
CD8 cells are thought to be immunopathogenic and drive the immune response. In vitro studies have shown a reduction of CD8+ and CD4+ cells in the presences of teriflunomide.
HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs)
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
HTLV-1 proviral load in the CSF cells
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
Change in IPEC score
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Change in EDSS score
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Change in 25-foot timed walk
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Full Information
NCT ID
NCT04799288
First Posted
March 13, 2021
Last Updated
May 20, 2023
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT04799288
Brief Title
Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
Official Title
Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
Study Type
Interventional
2. Study Status
Record Verification Date
May 18, 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 24, 2021 (Actual)
Primary Completion Date
August 31, 2025 (Anticipated)
Study Completion Date
August 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Background:
HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare, progressive disease. It occurs in some people infected with the HTLV-1 virus. It leads to weakness in the lower limbs and other serious problems. It has no treatment. Teriflunomide is a drug used to treat multiple sclerosis. It reduces immune cells that make the disease worse. Researchers want to learn if this drug can help people with HAM/TSP.
Objective:
To learn the effects, immune response, safety, and tolerability of teriflunomide in people with HAM/TSP.
Eligibility:
Adults ages 18 and older with HAM/TSP.
Design:
Participants will be screened under protocol 98-N-0047.
Participants will have a medical history. They will have physical and neurological exams. They will have blood and urine tests.
Participants will take 1 tablet of the study drug once a day for 9 months. They will keep a drug diary.
Participants will have lymphapheresis. For this, blood is drawn from a needle in one arm. A machine divides the blood into red cells, plasma, and white cells. The white cells are removed. The plasma and red cells are returned to the participant through a needle in the other arm.
Participants will have lumbar punctures ( spinal taps ). For this, a thin needle is inserted into the spinal canal in the lower back. Spinal fluid is removed.
Participants will have magnetic resonance imaging (MRI) of the brain and spine. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner.
Participation will last for 15 months.
Detailed Description
Study Description:
In this single center, single arm, open label, baseline versus treatment pilot clinical trial, sixteen subjects with HAM/TSP will receive teriflunomide 14mg by mouth once a day in an initial 9 month treatment phase, followed by a 3 month post treatment follow-up phase. Outcome measures will be collected every 3 months for the duration of the study.
Objectives:
We will determine the effects of teriflunomide, an FDA approved drug for the treatment of relapsing remitting multiple sclerosis that inhibits de novo pyrimidine synthesis, on immune activation markers in patients with HAM/TSP and the correlation of these with virological, radiological and clinical measures of disease burden .
Endpoints:
The primary outcome measure is ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide. Secondary outcome measures will include determination of immune activation patterns of PBMC and CSF using multicolor flow cytometric analysis and HTLV-I proviral load in blood and CSF. Safety and tolerability of teriflunomide will be assessed by tabulation of adverse events, clinical exam, standardized neurological disability scales (EDSS, IPEC, HAQ-DI), MR imaging of brain and spinal cord and clinical laboratory studies.
Study Population:
Up to 24 adults with HAM/TSP, targeting at least 16 participants who complete 9 months of treatment with teriflunomide
Phase:
I/II
Description of Sites/Facilities Enrolling Participants:
NIH Clinical Center
Description of Study Intervention:
Administration of teriflunomide 14mg daily for 9 months
Study Duration:
48 months
Participant Duration:
15 months
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HAM/TSP
Keywords
Aubagio, Single center, Open Label
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Teriflunomide
Arm Type
Experimental
Arm Description
Teriflunomide 14 mg daily
Intervention Type
Drug
Intervention Name(s)
Teriflunomide
Intervention Description
Teriflunomide 14mg will be administered orally as 1 tablet once daily during the 9-month treatment phase of the study.
Primary Outcome Measure Information:
Title
ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide
Description
ex vivo spontaneous lymphoproliferation of HAM/TSP patients receiving teriflunomide and multicolor flow cytometric analysis of immune activation markers in both PBMCs and CSF
Time Frame
Percent change between Day 0 and month 9 of spontaneous proliferation.
Secondary Outcome Measure Information:
Title
Tabulation of adverse events
Description
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of disease laboratory and clinical measures.
Time Frame
at each visit
Title
Percent change between CD8+ and CD4+ cells in the CSF
Description
CD8 cells are thought to be immunopathogenic and drive the immune response. In vitro studies have shown a reduction of CD8+ and CD4+ cells in the presences of teriflunomide.
Time Frame
between month -3 and month 9
Title
HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs)
Description
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
Time Frame
at month 9 and compared to Day 0
Title
HTLV-1 proviral load in the CSF cells
Description
HTLV-1 proviral load is a measure of the percent of infected cells and previous data suggests a correlation with disease activity.
Time Frame
at month 9 and compared to month -3
Title
Change in IPEC score
Description
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Time Frame
at month 9 and compared to Day 0
Title
Change in EDSS score
Description
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Time Frame
at month 9 and compared to Day 0
Title
Change in 25-foot timed walk
Description
This is a first in HAM/TSP pilot study using teriflunomide thus important to monitor for any unexpected events related to worsening of clinical measures.
Time Frame
at month 9 and compared to Day 0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
18 years or older
Diagnosis of HAM/TSP as defined by WHO criteria, including a positive HTLV-1 EIA and confirmatory Western Blot.
Enrolled in 98-N-0047
Patient must be willing and able to comply with all the aspects of trial design and follow-up.
Negative QuantiFERON-TB gold, or completion of latent tuberculosis infection treatment, per CDC and National TB Controllers Association recommendations
--In the event of an indeterminant result, the test will be repeated. Should two consecutive tests yield indeterminant results, a chest x-ray will be performed to rule out radiographic evidence of a latent TB infection. Negative imaging will enable the subject to qualify for participation in the study.
Ability to take oral medication and be willing to adhere to the protocol regimen
Patients must be able to provide informed consent
If able to become pregnant or to father a child, patient must agree to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or surgical sterilization (hysterectomy, tubal ligation, or vasectomy) for the duration of the treatment arm of the study and for two years following cessation of treatment with teriflunomide.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
Alternative diagnoses that can explain neurological disability
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial or interfere with participation for the full duration of the trial; or not in the best interest of the subject to participate, in the opinion of the treating investigator
Severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections.
Liver dysfunction, as indicated by baseline aspartate aminotransferase (AST) or alanine or alanine aminotransferase (ALT) greater than 2 times the upper limit of normal
Positive serological evidence of HIV, HTLV II, Hepatitis B or C
Treatment with immunomodulatory/immunosuppressive therapy (aside from topical steroids) in the preceding 6 months.
Pregnant or lactating women.
Treatment with other investigational drugs within 6 months before enrollment
Known hypersensitivity to teriflunomide or leflunomide
Concomitant treatment with leflunomide
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anita M Fletcher, M.D.
Phone
(301) 496-1801
Email
anita.fletcher@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Steven Jacobson, Ph.D.
Phone
(301) 496-0519
Email
jacobsons@ninds.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Jacobson, Ph.D.
Organizational Affiliation
National Institute of Neurological Disorders and Stroke (NINDS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY8664111010
Email
prpl@cc.nih.gov
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
.All IPD that results in a publication
IPD Sharing Time Frame
6 months after publication
IPD Sharing Access Criteria
IPD will be shared under tech transfer agreements.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2021-N-0016.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
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