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Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis

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ClinicalTrials.gov Identifier: NCT04799288
Recruitment Status : Recruiting
First Posted : March 16, 2021
Last Update Posted : January 4, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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.


Condition or disease Intervention/treatment Phase
HAM/TSP Drug: Teriflunomide Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
Actual Study Start Date : September 24, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Teriflunomide
Teriflunomide 14 mg daily
Drug: Teriflunomide
Teriflunomide 14mg will be administered orally as 1 tablet once daily during the 9-month treatment phase of the study.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. HTLV-1 proviral load in the peripheral blood mononuclear cells (PBMCs) [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  2. Change in IPEC score [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  3. Change in EDSS score [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  4. Change in 25-foot timed walk [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  5. Tabulation of adverse events at each visit [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  6. HTLV-1 proviral load in the CSF cells [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.

  7. Percent change between baseline and month 9 of the percent of CD8+ cells in the CSF [ Time Frame: change from month 9 compared to baseline ]
    collect and analyze additional clinical and biological data relevant to the safety and tolerability of teriflunomide as well as clinical benefit.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04799288


Contacts
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Contact: Joan M Ohayon, C.R.N.P. (301) 496-3825 eatonj@ninds.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Steven Jacobson, Ph.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT04799288    
Other Study ID Numbers: 210016
21-N-0016
First Posted: March 16, 2021    Key Record Dates
Last Update Posted: January 4, 2022
Last Verified: December 21, 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Aubagio
Single center
Open Label
Additional relevant MeSH terms:
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Paraparesis, Tropical Spastic
Spinal Cord Diseases
Paraparesis
Paraparesis, Spastic
Neurologic Manifestations
Nervous System Diseases
Central Nervous System Diseases
Paresis
Myelitis
Central Nervous System Infections
Infections
HTLV-I Infections
Deltaretrovirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Teriflunomide
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors