A Study of KW-0761 in Subjects With HTLV-1 Associated Myelopathy (HAM)
- Conditions
- HTLV-1 Associated Myelopathy
- Interventions
- Drug: KW-0761 0.3 mg/kg IVDrug: Placebo (saline)
- Registration Number
- NCT03191526
- Lead Sponsor
- Kyowa Kirin Co., Ltd.
- Brief Summary
The objective of this study is to assess the efficacy and safety of KW-0761 after intravenous injections in subjects with HTLV-1 associated myelopathy (HAM) in Japan.
- Detailed Description
The effects of KW-0761 (0.3 mg/kg) on the Osame's motor disability score (OMDS) of subjects with HTLV-1 associated myelopathy (HAM).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 66
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Voluntary written informed consent to participate in the study
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Diagnosis as HAM according to the second edition of HAM Treatment Manual
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At least 1-year history of HAM
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Ongoing medication*1 for HAM, with no changes in 3 months before enrollment; or inadequate response or intolerance to prior medication,*2 which must have been discontinued for at least 3 months before enrollment. Subjects on maintenance therapy with steroids must have been receiving ≤ 10 mg/day prednisolone equivalent continuously for at least 3 months before enrollment.
- 1 Steroids, salazosulfapyridine, or ≥ 1.5 g/day vitamin C
- 2 Steroids, Interferon-α, salazosulfapyridine, or ≥ 1.5 g/day vitamin C
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No change in the degree of motor dysfunction for at least 3 months before the date of screening, as judged by the investigator or subinvestigator
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A OMDS of ≥3 at screening and able to walk ≥10 m at screening (use of a single cane or double canes is allowed)
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Any of the following significant concomitant diseases:
Type 1 diabetes mellitus, Poorly controlled type 2 diabetes mellitus (HbA1c (NGSP) > 8.5%), Congestive heart failure (Class II to IV of the New York Heart Association Functional Classification), Myocardial infarction within 1 year before enrollment, Unstable angina within 1 year before enrollment, Poorly controlled hypertension (systolic blood pressure > 150 mm Hg and diastolic blood pressure > 90 mm Hg at screening), Sever chronic lung disease requiring oxygen therapy, Multiple sclerosis or any other demyelinating disease, Epilepsy requiring treatment with antiepileptics (with the exception of epilepsy controlled by antiepileptics, with no occurrence of seizures for at least 3 years before informed consent), and Active malignancy (including ATL); or onset of malignancy or previous treatment for malignancy (with the exception of resected or surgically cured intraepithelial carcinoma of the uterine cervix, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or ductal breast carcinoma) within 5 years before informed consent
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Active infection
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Concurrent spinal cord compression lesion (e.g., cervical spine diseases, disk herniation, or ossification of the ligamentum flavum) , with the exception of conditions that would not affect efficacy evaluation in the study, as judged by the investigator or subinvestigator
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Concurrent dementia
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Concurrent psychiatric disorder, with the exception of conditions that would not affect obtaining informed consent or efficacy evaluation in the study, as judged by the investigator or subinvestigator
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History of or current alcohol or drug dependence
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Planned surgery during the study period
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Any other conditions unsuitable for participation in the study in the opinion of the investigator or subinvestigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KW-0761 0.3 mg/kg IV KW-0761 0.3 mg/kg IV Intravenous injection every 12 weeks. Duration of double-blind treatment is going to be for 24 weeks and be followed by transitional period, which is for maximal 4 weeks. After that, duration of open label treatment is going to be conducted for 24 weeks. And an extension treatment will be continued until the approval or termination. Placebo (saline) Placebo (saline) Intravenous injection every 12 weeks. Duration of double-blind treatment is going to be for 24 weeks and be followed by transitional period, which is for maximal 4 weeks. After that, duration of open label treatment is going to be conducted for 24 weeks. And an extension treatment will be continued until the approval or termination.
- Primary Outcome Measures
Name Time Method Improvement in Osame's motor disability score At week 4, 8 and 12 after second injection
- Secondary Outcome Measures
Name Time Method Modified Ashworth Scale Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of Urinary dysfunction (OABSS) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of Urinary dysfunction (I-PSS) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose HTLV-1 Proviral load in peripheral blood Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Mean of twice 10 m walking time Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of Clinical Global Impression (CGI-I) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of Clinical Global Impression (VAS) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of sensory dysfunction (numbness in the lower limbs (VAS)) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Evaluation of sensory dysfunction (Pain in the lower limbs (VAS)) Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose Neopterine Concentration in CSF At week 12
Trial Locations
- Locations (16)
Kansai Medical University Hosipital
🇯🇵Hirakata, Osaka Prefecture, Japan
University Hosipital, Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
University of the Ryukyus Hospital
🇯🇵Nakagami, Okinawa Prefecture, Japan
National Hospital Organization Okinawa National Hospital
🇯🇵Ginowan, Okinawa Prefecture, Japan
Oita Prefectural Hospital
🇯🇵Oita, Oita Prefecture, Japan
Ehime University Hospital
🇯🇵Tone, Ehime, Japan
Nagoya University Hosipital
🇯🇵Nagoya, Aichi, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Fukuoka Prefecture, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Fukuoka Prefecture, Japan
Kagoshima City Hospital
🇯🇵Kagoshima, Kagoshima Prefecture, Japan
Hospital of the University of Occupational and Environmental Health, Japan
🇯🇵Kitakyushu, Fukuoka, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kawasaki, Kanagawa Prefecture, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Kumamoto Prefecture, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Kagoshima Prefecture, Japan
Fujimoto General Hospital
🇯🇵Miyakonojō, Miyazaki, Japan
Tohoku University Hosipital
🇯🇵Sendai, Miyagi Prefecture, Japan