HAM/TSPPhase 1/2NCT04799288
Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
A Phase 1/2 study testing Teriflunomide in people with HAM/TSP, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- HAM/TSP
- What is being tested?
- Teriflunomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Sep 2021to 31 Dec 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 a positive test result
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- --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.
Who cannot join
- 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
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- Treatment with immunomodulatory/immunosuppressive therapy is exclusionary except in the cases below:
- current use of topical steroids
- Study participants who have been prescribed <= 10 mg prednisone (PO) per day will be required to discontinue this medication for a period of at least 3 months (90 days) prior to enrolling in 21-N-0016. Additionally, participants who have been prescribed burst therapy with an oral steroid as an outpatient over the course of <= 10 days (e.g., Medrol Dosepak [methylprednisolone]), can enroll after discontinuing burst dose oral steroids for at least 3 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Official title: Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
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.
Read more
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.
Read the 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.
- Conditions
- HAM/TSP
- Being tested
- Teriflunomide
- Keywords
- Aubagio, Single center, Open Label
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TeriflunomideDrug
Teriflunomide 14mg will be administered orally as 1 tablet once daily during the 9-month treatment phase of the study.
| Study group | Role | What they receive |
|---|---|---|
| Teriflunomide | Experimental | Teriflunomide 14 mg daily Receives: Drug: Teriflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Percent change between Day 0 and month 9 of spontaneous proliferation.
Secondary outcomes (7)
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.
Measured: at each visit
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.
Measured: between month -3 and month 9
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.
Measured: at month 9 and compared to Day 0
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.
Measured: at month 9 and compared to month -3
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.
Measured: at month 9 and compared to Day 0
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.
Measured: at month 9 and compared to Day 0
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.
Measured: at month 9 and compared to Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2021
- Study start24 Sep 2021
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HAM/TSPStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Steven Jacobson, Ph.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04799288
- Sponsor's protocol ID
- 210016
- Other IDs
- 21-N-0016
- Status last verified
- 29 Oct 2026
- First submitted
- 13 Mar 2021
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
- ClinicalTrials.gov ID
- NCT04799288
- Acronym / sponsor ID
- 210016
- Conditions
- HAM/TSP
- Keywords
- Aubagio, Single center, Open Label
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 24 Sep 2021 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 16 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Teriflunomide | Experimental | Drug: TeriflunomideTeriflunomide 14 mg daily |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TeriflunomideTeriflunomide 14mg will be administered orally as 1 tablet once daily during the 9-month treatment phase of the study. | Drug | Teriflunomide |
Primary outcome
ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide
Time frame: Percent change between Day 0 and month 9 of spontaneous proliferation.
ex vivo spontaneous lymphoproliferation of HAM/TSP patients receiving teriflunomide and multicolor flow cytometric analysis of immune activation markers in both PBMCs and CSF
7 secondary outcomes
Tabulation of adverse events
Time frame: at each visit
Percent change between CD8+ and CD4+ cells in the CSF
Time frame: between month -3 and month 9
HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs)
Time frame: at month 9 and compared to Day 0
HTLV-1 proviral load in the CSF cells
Time frame: at month 9 and compared to month -3
Change in IPEC score
Time frame: at month 9 and compared to Day 0
Change in EDSS score
Time frame: at month 9 and compared to Day 0
Change in 25-foot timed walk
Time frame: at month 9 and compared to Day 0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All IPD that results in a publication
Related trials for HAM/TSP
RecruitingObservational study
Evaluation of Patients With HAM/TSP
HTLV-I Infection, Tropical Spastic Paraparesis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Steven Jacobson, Ph.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Teriflunomide in people with HAM/TSP, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christopher Y Itoh, M.D. ((301) 496-3825, christopher.itoh@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ex vivo spontaneous lymphoproliferation in HAM/TSP patients receiving teriflunomide (time frame: Percent change between Day 0 and month 9 of spontaneous proliferation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.