Clinical trial NCT03191526: A Study of KW-0761 in Subjects With HTLV-1 Associated Myelopathy (HAM)
Official title: A Phase 3 Multicenter, Randomized, Double-Blind and Placebo-Controlled Study, and Open Study of KW-0761 in Patients With HTLV-1 Associated Myelopathy (HAM)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HTLV-1 Associated Myelopathy
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-06-19
Enrollment: 66
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Voluntary written informed consent to participate in the study
2. Diagnosis as HAM according to the second edition of HAM Treatment Manual
3. At least 1-year history of HAM
4. 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
5. 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
6. A OMDS of ≥3 at screening and able to walk ≥10 m at screening (use of a single cane or double canes is allowed)

Exclusion Criteria:

1. 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
2. Active infection
3. 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
4. Concurrent dementia
5. 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
6. History of or current alcohol or drug dependence
7. Planned surgery during the study period
8. Any other conditions unsuitable for participation in the study in the opinion of the investigator or subinvestigator

Primary outcomes:
measure: Improvement in Osame's motor disability score
timeFrame: At week 4, 8 and 12 after second injection
Secondary outcomes:
measure: HTLV-1 Proviral load in peripheral blood
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Mean of twice 10 m walking time
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Modified Ashworth Scale
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of Clinical Global Impression (CGI-I)
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of Clinical Global Impression (VAS)
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of Urinary dysfunction (OABSS)
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of Urinary dysfunction (I-PSS)
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of sensory dysfunction (numbness in the lower limbs (VAS))
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Evaluation of sensory dysfunction (Pain in the lower limbs (VAS))
timeFrame: Pre-dose, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 weeks post-dose
measure: Neopterine Concentration in CSF
timeFrame: At week 12
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hosipital
state: Aichi
city: Tone
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
state: Fukuoka Prefecture
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
state: Fukuoka Prefecture
city: Kitakyushu
country: Japan
facility: Hospital of the University of Occupational and Environmental Health, Japan
state: Fukuoka
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital
state: Kagoshima Prefecture
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
state: Kagoshima Prefecture
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kanagawa Prefecture
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
state: Kumamoto Prefecture
city: Sendai
country: Japan
facility: Tohoku University Hosipital
state: Miyagi Prefecture
city: Miyakonojō
country: Japan
facility: Fujimoto General Hospital
state: Miyazaki
city: Oita
country: Japan
facility: Oita Prefectural Hospital
state: Oita Prefecture
city: Ginowan
country: Japan
facility: National Hospital Organization Okinawa National Hospital
state: Okinawa Prefecture
city: Nakagami
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa Prefecture
city: Hirakata
country: Japan
facility: Kansai Medical University Hosipital
state: Osaka Prefecture
city: Kyoto
country: Japan
facility: University Hosipital, Kyoto Prefectural University of Medicine
Study officials:
References: