Teriflunomide for Tropical Spastic Paraparesis

Overseen By Daniel S Reich, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Must not be taking: Immunosuppressives, Leflunomide

Disqualifiers: HIV, Hepatitis B, Liver dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 9 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if teriflunomide, a drug typically used for multiple sclerosis, can benefit individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), which causes weakness in the lower limbs. Researchers seek to understand the drug's effects on the immune system and assess its safety and tolerability for those with HAM/TSP. Individuals diagnosed with HAM/TSP who are willing to adhere to the trial process may be suitable candidates. Participants will take a tablet daily for 9 months and undergo various tests and procedures over 15 months. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications. If you are taking prednisone or other oral steroids, you must stop them at least 3 months before joining the trial. Other immunomodulatory or immunosuppressive therapies are also not allowed.

Is there any evidence suggesting that teriflunomide is likely to be safe for humans?

Research has shown that teriflunomide is generally well-tolerated by people with certain conditions. In studies involving patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), teriflunomide showed promising results. It reduced the virus in the body, improved walking, and managed bladder issues like constipation.

Teriflunomide is already used to treat multiple sclerosis, so its safety profile is well-known. However, when used for HAM/TSP, specific study data should be considered. While side effects can occur with any treatment, research suggests that teriflunomide is manageable for most people in these trials. Medical exams and disability scales monitored participants to ensure safety.

Those considering joining a trial should discuss potential risks and benefits with their healthcare provider, who can offer personalized advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Tropical Spastic Paraparesis, which typically involve managing symptoms with medications like corticosteroids or antiretrovirals, Teriflunomide offers a new approach. Teriflunomide is unique because it is an oral medication that works by inhibiting the proliferation of certain immune cells, potentially reducing inflammation and nerve damage associated with the condition. This mechanism is different from current options and could provide a more targeted way to slow disease progression. Researchers are excited about its potential to offer a more convenient and effective treatment option for patients.

What evidence suggests that teriflunomide might be an effective treatment for HAM/TSP?

Studies have shown that teriflunomide can benefit people with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). It reduces the amount of virus in the body. Patients taking teriflunomide experienced improvements in disability levels and walking speed. This drug already treats multiple sclerosis by reducing harmful immune cells, which might explain its potential benefits for HAM/TSP. However, some research noted little effect on certain immune markers in this condition. Overall, early findings suggest that teriflunomide could help manage HAM/TSP symptoms. ^{1 4 5 6 7}

Who Is on the Research Team?

Steven Jacobson, Ph.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

Adults over 18 with HAM/TSP, a rare disease linked to HTLV-1 virus causing lower limb weakness. Participants must be able to take oral meds, follow the trial design, and use reliable birth control if necessary. Excluded are those with severe immune or liver issues, other conditions that could affect results, or recent immunomodulatory drugs usage.

Inclusion Criteria

Enrolled in 98-N-0047

I can take pills and will follow the treatment plan.

Patient must be willing and able to comply with all aspects of trial design and follow-up

Exclusion Criteria

Pregnant or lactating women

I haven't taken immune-suppressing drugs recently, except for low-dose prednisone or topical steroids.

My liver tests are more than twice the normal limit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive teriflunomide 14 mg daily for 9 months

9 months

Visits every 3 months (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Visits every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Teriflunomide

Trial Overview The study tests teriflunomide's effectiveness on HAM/TSP by monitoring effects and immune response over 9 months of daily tablet intake. It includes blood/urine tests, lymphapheresis (white cell removal), spinal taps for fluid analysis, and MRI scans of brain/spine.

How Is the Trial Designed?

Group I: Teriflunomide Experimental Treatment 1 Intervention

Teriflunomide 14 mg daily

Teriflunomide is already approved in United States, European Union for the following indications:

Approved in United States as Aubagio for:

• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults

Approved in European Union as Aubagio for:

• Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

This study reports the first two diagnosed cases of tropical spastic paraparesis associated with HTLV-I in Cuiabá, Brazil, highlighting the presence of this condition in a new geographic area.

One patient showed a positive response to treatment with prednisone, suggesting that corticosteroids may be beneficial in managing symptoms of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tropical spastic paraparesis/HTLV-I associated myelopathy. Report of 2 cases diagnosed in Cuiabá, Mato Grosso, Brazil]. Grzesiuk, AK., Martins, Pde D.[2019]

Teriflunomide (Aubagio®) is an effective once-daily oral treatment for relapsing forms of multiple sclerosis (RMS), approved in multiple regions including Europe and North America.

The review discusses teriflunomide's safety and efficacy based on extensive clinical trials, while also exploring its therapeutic mechanism of action, which is still being researched through various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. Bar-Or, A.[2021]

Teriflunomide (Aubagio®) is an oral medication that works by targeting the mitochondrial enzyme dihydroorotate dehydrogenase, helping to modulate the immune response in patients with relapsing-remitting multiple sclerosis (MS).

On June 18, 2021, teriflunomide was approved for use in pediatric patients aged 10 years and older in the EU, marking a significant milestone in its development for treating MS in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. Paik, J.[2021]

In a study of 1128 patients with relapsing-remitting multiple sclerosis, teriflunomide significantly reduced the annualized relapse rate from 0.87 to 0.35 over 24 months, indicating its effectiveness in managing the disease.

Patient satisfaction with teriflunomide was high, with significant improvements in effectiveness, convenience, and overall satisfaction reported after 24 months, while the safety profile was consistent with previous clinical trials, with 35.8% experiencing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. Kallmann, BA., Tiel-Wilck, K., Kullmann, JS., et al.[2022]

In a real-world study involving 200 patients with relapsing multiple sclerosis, teriflunomide demonstrated stable quality of life over 24 months, with significant reductions in relapse activity compared to the pre-baseline period.

The study indicated high treatment adherence and acceptability of teriflunomide, as reflected in patient-reported outcomes, with no substantial changes in fatigue and a marginal increase in reported disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. Hestvik, ALK., Frederiksen, JL., Nielsen, HH., et al.[2022]

Tropical spastic paraparesis associated with HTLV-I (TSP/HAM) is rare in Europe, primarily affecting first- or second-generation immigrants from endemic regions, with a seroprevalence of less than 0.03% among blood donors.

In Africa, where HTLV-I is endemic, there are few reported cases of TSP/HAM despite millions of infected individuals, likely due to limited healthcare resources and a lack of comprehensive epidemiological studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tropical spastic paraparesis/HTLV-I-associated myelopathy in Europe and in Africa: clinical and epidemiologic aspects. Touzé, E., Gessain, A., Lyon-Caen, O., et al.[2019]

A patient with HTLV-1-associated myelopathy (HAM/TSP) showed significant improvement in mobility after treatment with Combivir (lamivudine-zidovudine), transitioning from walker dependence to using only a cane.

This case suggests that lamivudine-zidovudine may have potential therapeutic benefits for patients with HAM/TSP, warranting further investigation into its efficacy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tropical spastic paraparesis treated with Combivir (lamivudine-zidovudine). Hassan, S., Amer, S., Zervos, M.[2013]

Teriflunomide is an effective oral treatment for relapsing multiple sclerosis, showing better efficacy than placebo and comparable effectiveness to interferon beta-1a in preventing relapses and disability progression, based on phase III trials.

While generally well tolerated, teriflunomide can increase liver enzyme levels and is contraindicated in pregnancy due to potential teratogenic risks, highlighting the need for careful monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teriflunomide: a review of its use in relapsing multiple sclerosis. Garnock-Jones, KP.[2021]

Tropical spastic paraparesis (TSP) is a chronic disease linked to the human T lymphotropic virus type 1 (HTLV-1), primarily affecting adults, especially women, and often leads to significant disability within 10 years.

The disease is characterized by progressive spastic paraparesis and associated symptoms, with histological findings showing chronic inflammation and demyelination in the spinal cord, indicating a severe impact on neurological function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HTLV-1 and tropical spastic paraparesis. 1. Clinical features, pathology and epidemiology. Montgomery, RD.[2019]

This study reports the first two diagnosed cases of tropical spastic paraparesis associated with HTLV-I in Florianópolis, Brazil, highlighting the importance of recognizing this condition in new regions.

One patient showed a positive response to treatment with methylprednisolone, suggesting that corticosteroids may be effective in managing symptoms of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[HTLV-I-associated myelopathy/tropical spastic paraparesis: report of 2 cases diagnosed in Florianópolis, Santa Catarina, Brazil]. Coral, LC., de Queiroz, LP., Grzesiuk, AK.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04799288

Teriflunomide in HTLV-1 Associated Myelopathy/Tropical ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40347230

Safety and efficacy of teriflunomide on clinical course ... Conclusions: Teriflunomide effectively reduced the proviral load, improved the severity of disability and walking speed, and better controlled ...

3. researchgate.net researchgate.net/publication/391635539_Safety_and_efficacy_of_teriflunomide_on_clinical_course_and_laboratory_findings_in_patients_with_HTLV-1-associated_myelopathytropical_spastic_paraparesis_a_triple-blind_study

Safety and efficacy of teriflunomide on clinical course ... Conclusions Teriflunomide effectively reduced the proviral load, improved the severity of disability and walking speed, and better controlled ...

4. neurology.org neurology.org/doi/10.1212/NXI.0000000000000986

Effect of Teriflunomide on Cells From Patients With Human ... These results demonstrate that teriflunomide had minimal effect on the immune activation marker CD25 of patients with HAM/TSP during these ...

5. tandfonline.com tandfonline.com/doi/full/10.2217/nmt-2021-0014

An Updated Review of teriflunomide's Use in Multiple ... Teriflunomide, a treatment taken orally once a day, has shown consistent effectiveness and safety in patients with relapsing forms of multiple sclerosis (MS).

6. link.springer.com link.springer.com/article/10.1007/s00415-025-13134-9

Safety and efficacy of teriflunomide on clinical course ... Teriflunomide effectively reduced the proviral load, improved the severity of disability and walking speed, and better controlled urinary and constipation ...

7. htlv.net htlv.net/safety-and-efficacy-of-teriflunomide-on-clinical-course-and-laboratory-findings-in-patients-with-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-a-triple-blind-study/

Safety and efficacy of teriflunomide on clinical course ... Teriflunomide effectively reduced the proviral load, improved the severity of disability and walking speed, and better controlled urinary and constipation ...