Teriflunomide for Tropical Spastic Paraparesis
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Approved in 2 Jurisdictions
Trial Summary
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.
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.
12345How 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.
678910Eligibility 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
+5 more
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.
+7 more
Trial 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)
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: TeriflunomideExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Neurological Disorders and Stroke (NINDS)Lead Sponsor
References
Teriflunomide (Aubagio®) for the treatment of multiple sclerosis. [2021]Teriflunomide (Aubagio®) is a once-daily oral immunomodulatory disease modifying therapy (DMT) presently approved in several regions, including Europe, North America, Latin America and Australia, for the treatment of relapsing forms of multiple sclerosis (RMS; RRMS). The therapeutic mode of action of teriflunomide in MS continues to be investigated. This review summarizes the main efficacy and safety results of the clinical trial program leading to teriflunomide's approval, highlights a number of practical clinical considerations, and overviews its presumed therapeutic mode of action (MOA) based on pharmacokinetic and pharmacodynamic observations and the growing body of teriflunomide-related in vitro, pre-clinical (animal model), and in vivo human studies.
Real-world study of relapsing-remitting multiple sclerosis patients treated with Teriflunomide in Nordic countries: Quality-Of-Life, efficacy, safety and adherence outcomes. [2022]Teriflunomide 14 mg (Aubagio®) is a once-daily, oral drug approved for the treatment of relapsing forms of multiple sclerosis (MS). While the efficacy and safety of teriflunomide have been thoroughly characterised across an extensive clinical program, we were interested in studying performance of the drug with respect to quality-of-life (QoL) outcomes in persons with MS in a real-world setting.
Teriflunomide: Pediatric First Approval. [2021]Teriflunomide (Aubagio®), which was developed by Sanofi, is an oral immunomodulatory agent targeting the mitochondrial enzyme dihydroorotate dehydrogenase and available to adults to treat relapsing-remitting multiple sclerosis (MS). On 18 June 2021, teriflunomide received its first approval in this indication in pediatric patients aged ≥ 10 years in the EU. This article summarizes the milestones in the development of teriflunomide leading to this first pediatric approval for relapsing-remitting MS.
Real-life outcomes of teriflunomide treatment in patients with relapsing multiple sclerosis: TAURUS-MS observational study. [2022]Teriflunomide is a once-daily oral immunomodulatory agent approved for the treatment of relapsing-remitting multiple sclerosis (MS). We aimed to obtain data on the effectiveness, tolerability, and subject satisfaction with teriflunomide (Aubagio®) under clinical practice conditions in unselected MS patients.
Teriflunomide: a review of its use in relapsing multiple sclerosis. [2021]Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data can be extrapolated from the large amount of post-approval data available regarding its parent drug. Oral teriflunomide is a valuable addition to available treatment options for patients with relapsing multiple sclerosis, in particular those patients who prefer an oral drug.
[Tropical spastic paraparesis/HTLV-I associated myelopathy. Report of 2 cases diagnosed in Cuiabá, Mato Grosso, Brazil]. [2019]We describe two cases of tropical spastic paraparesis/HTLV-I associated myelopathy, according to the criteria of World Health Organization-1989. These are the first cases diagnosed in Cuiabá (Mato Grosso State, Brazil). One of them had a good response with the treatment with prednisone.
[HTLV-I-associated myelopathy/tropical spastic paraparesis: report of 2 cases diagnosed in Florianópolis, Santa Catarina, Brazil]. [2019]We describe two cases of tropical spastic paraparesis/HTLV-I associated myelopathy, according to the criteria of World Health Organization-1989. These are the first cases diagnosed in Florianópolis (Santa Catarina State-Brazil). One of them had a good response with the treatment with methylprednisolone.
Tropical spastic paraparesis/HTLV-I-associated myelopathy in Europe and in Africa: clinical and epidemiologic aspects. [2019]We review here the epidemiologic and clinical aspects of tropical spastic paraparesis, human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) as observed in Europe and in Africa. Europe is not an endemic region for HTLV-I (seroprevalence in blood donors,
Tropical spastic paraparesis treated with Combivir (lamivudine-zidovudine). [2013]Tropical spastic paraparesis (TSP) or human T-cell leukemia virus-type 1 (HTLV-I)-associated myelopathy is caused by human T-lymphotropic virus type 1. It is a slow, progressive spastic paraparesis with significant morbidity and causing profound repercussions on quality of life. No therapies have been found to persistently improve the outcome in these patients. We present a patient with HTLV-1-associated myelopathy/TSP (HAM/TSP) who was treated with Combivir (lamivudine-zidovudine, GlaxoSmithKline, London, UK). She was walker-dependent for several years but, soon after treatment with lamivudine-zidovudine, was able to walk using only a cane. The role of lamivudine-zidovudine should be investigated further in this patient population.
HTLV-1 and tropical spastic paraparesis. 1. Clinical features, pathology and epidemiology. [2019]The clinical profile of tropical spastic paraparesis (TSP), described in scattered tropical and subtropical territories over the past 30 years, has been more clearly defined since the discovery of its direct association with human T lymphotropic virus type 1 (HTLV-1). A chronic disease of adults, commoner in women, it usually presents as a progressive spastic paraparesis with sphincter disturbance, sometimes with backache and lower limb sensory disorder. Most cases are chair-bound within 10 years. Histology reveals a chronic lymphocytic meningomyelopathy, predominantly in the spinal cord, together with long tract demyelination and hyalinoid thickening of the media and adventitia of small blood vessels. Geographical areas of high prevalence of TSP are known in the Caribbean, South America, South Africa, southern Japan, the Seychelles and probably in India, and it is sparsely endemic elsewhere. The virus appears to exist within lymphocytes for long periods. Vertical transmission occurs postnatally, and sexual and transfusion infection are also recognized, but much remains to be clarified regarding its pathogenesis and epidemiology.