Efficacy and Safety of Tamibarotene(AM80H) for HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)

Study Overview
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Brief Summary
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An open-label, non-randomised, uncontrolled, proof-of-concept study of patients with HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Participants will receive oral administration of tamibarotene in the amount of 2 mg daily over a period of 12 weeks, then 4mg daily for another 12 weeks. The patients will be followed up for further 8 weeks. Efficacy will be monitored by measuring clinical scores including motor and urination function, HTLV-1 proviral load, immunological parameters, and markers in the spinal fluid. Safety will be evaluated at the same time.

Official Title
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Open-Label, Exploratory Study of the Efficacy and Safety of Tamibarotene(AM80H) for HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)

Conditions
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HTLV-I-Associated Myelopathy

Intervention / Treatment
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* Drug: Tamibarotene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been diagnosed as HAM according to the WHO criteria Patients who are positive for HTLV-I antibody in the spinal fluid Patients, if female, who are not pregnant or breastfeeding, either agreed to take contraceptive measures during and two years after the treatment, or sterile Patients, if male, who agreed to take contraceptive measures during and six months after the treatment Patients who have been informed and understood the contents of the study and consented to participate in the signed form. Exclusion Criteria: Patients who has a rapid progress in the symptoms defined as an increase of two or more in Osame's Motor Disability Score for HAM patients in the past one year. Patients of hyperlipidemia (serum triglyceride higher than 400 mg/dL) Patients who were administered new or increased dose of corticosteroid in the past 8 weeks before the intervention Patients who received steroid pulse therapy in the past 8 weeks before the intervention Patients who were administered new or increased dose of immunosuppressant in the past 8 weeks before the intervention Patients with a history of serious drug allergy Patients with significant complication such as malignancy, severe heart failure, and other serious diseases. Patients who were in the past administered etretinate.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tamibarotene|Oral administration of tamibarotene 2 mg daily over a period of 12 weeks, then 4mg daily for another 12 weeks.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Soluble IL-2 Receptor level in peripheral blood |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in HTLV-I viral load in peripheral blood |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in T cell population in peripheral blood |  | 0,12, 24, 28 and 32 weeks | 
| Change in cerebrospinal fluid examination |  | baseline and after the treatment defined as from 24 to 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Osame's Motor Disability Score for HAM patients |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in The Expanded Disability Status Scale (EDSS) |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in timed 10m walk |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in Manual Muscle Testing and vibratory perception of the lower limbs |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in Modified Ashworth Scale |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 
| Change in Urination function and defecation score |  | 0, 4, 8, 12, 16, 20, 24, 28 and 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAM, Tropical Spastic Paraparesis, TSP