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

Trial Summary

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 Teriflunomide generally safe for humans?

Teriflunomide, also known as Aubagio, is generally well tolerated in patients with multiple sclerosis, but it can cause increased liver enzyme levels and is not safe for pregnant women due to potential risks to the unborn baby. Long-term safety data is limited, but information from its parent drug, leflunomide, suggests it is safe for long-term use. ^{1 2 3 4 5}

How does the drug Teriflunomide differ from other treatments for tropical spastic paraparesis?

Teriflunomide is unique because it is primarily used for multiple sclerosis and works by reducing the activity of immune cells, which may help in conditions like tropical spastic paraparesis where the immune system is involved. Unlike other treatments like prednisone or methylprednisolone, which are steroids, Teriflunomide is not a steroid and has a different mechanism of action. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Research Team

Steven Jacobson, Ph.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021]

2. Netherlands 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Teriflunomide: Pediatric First Approval. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Teriflunomide: a review of its use in relapsing multiple sclerosis. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

[HTLV-I-associated myelopathy/tropical spastic paraparesis: report of 2 cases diagnosed in Florianópolis, Santa Catarina, Brazil]. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Tropical spastic paraparesis/HTLV-I-associated myelopathy in Europe and in Africa: clinical and epidemiologic aspects. [2019]

9. Scotland pubmed.ncbi.nlm.nih.gov

Tropical spastic paraparesis treated with Combivir (lamivudine-zidovudine). [2013]

10. England pubmed.ncbi.nlm.nih.gov

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