A Clinical Pharmacological Study of MT-3921 in Subjects With HTLV-1 Associated Myelopathy (HAM)

Study Overview
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Brief Summary
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The purposes of this study is to assess the safety, tolerability, and pharmacokinetics of MT-3921 in subjects with Human T-cell Leukemia Virus Type 1 (HTLV-1)-Associated Myelopathy(HAM). Subjects meeting eligibility criteria will enter the 6-month double-blind period. Subjects will be randomized in a 2:1 ratio to receive MT-3921 or placebo in a double blind manner.

Official Title
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A Clinical Pharmacological Study of MT-3921 in Subjects With Human T-cell Leukemia Virus Type 1 (HTLV-1)-Associated Myelopathy (HAM)

Conditions
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HTLV-1-Associated Myelopathy (HAM)

Intervention / Treatment
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* Biological: MT-3921
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Additional screening criteria check may apply for qualification: Subjects aged 20 years or older on the day of consent Subjects with a confirmed diagnosis of HAM according to the diagnostic algorithm of Practical Guideline for HAM 2019 on the day of consent Subjects with an Osame's motor disability score (OMDS) of ≥4 and ≤6 at Screening and on the first day of the Treatment period (predose) Subjects with no change in OMDS for at least 3 months before the day of consent Subjects with a CSF concentration neopterin of ≥6 pmol/mL at Screening Subjects on maintenance oral steroid therapy who have continued to receive the same dose equivalent to ≤10 mg/day of prednisolone for at least 3 months before the day of consent Exclusion Criteria: Additional screening criteria check may apply for qualification: Subjects who have a history of anaphylaxis or clinically significant allergic reactions due to administration of antibody products Subjects exhibiting or with a history of malignant tumor. Subjects with adult T-cell leukemia/lymphoma (ATL) or those with positive HTLV-1 clonality test (Southern blot) at screening and suspected of having ATL Subjects with spinal cord compression lesions, such as cervical spine disease, disc herniation, and ossification of the yellow ligament Subjects with psychiatric disorders, epileptic seizures, or dementia. Subjects with suicide attempts or suicidal ideation corresponding to item 4 or 5 on the Columbia Suicide Rating Scale (C-SSRS) at screening and/or on the first day of the Treatment period (predose) Subjects exhibiting or with a history of hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Subjects with the novel Coronavirus disease 2019 (COVID-19) Subjects with severe illness Male or female subjects of childbearing potential who do not agree to use a contraceptive measure from the day of consent to 16 weeks after the last dose of the investigational medical product Female subjects who are pregnant, lactating, or may be pregnant Subjects who have received anti-repulsive guidance molecule (RGM) a antibody containing this investigational medical product Subjects who participated in other clinical studies (including clinical trials) and received drugs (including investigational medical products) or therapy within 12 weeks before the day of consent

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT-3921<br>Intravenous (IV) | Biological: MT-3921<br>* Solution for infusion; Intravenous (IV)<br>* Other names: Unasnemab;|
| Placebo Comparator: Placebo<br>Intravenous (IV) | Biological: Placebo<br>* Solution for infusion; Intravenous (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with adverse events |  | 36 weeks | 
| Percentage of subjects with adverse reactions |  | 36 weeks | 
| Serum concentrations of MT-3921 |  | PK samples will be collected at predose, 1.5 hours, 2, 4, 8, 12, 20 (predose and 1.5 hours), 24, 36 weeks post-dose. | 
| CSF concentrations of MT-3921 |  | PK samples will be collected at 2, 4, 12, 24 weeks post-dose. |