HTLV-1-Associated-Myelopathy Tropical Spastic Paraparesis (HAM/TSP)
Conditions
Interventions
Sponsors
St. Marianna University School of Medicine Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: PhaseI (1)Patients diagnosed with HAM according to the WHO guideline and who meet the following criterion: Positive for HTLV-1(in serum and cerebrospinal fluid) (2)Patients diagnosed with HAM one year ago or earlier (3)Patients undergoing steroid maintenance therapy who meet the following criteria; -10mg/day or less of prednisolone for at least three months -Cerebrospinal fluid neopterin level is at or below 5pmol/mL -Cerebrospinal fluid neopterin level immediately before enrollment has not fluctuated beyond 60% of the levels measured three or more months before enrollment. The levels must be measured during steroid maintenance therapy. The following patients are excluded: -Patients who received steroid pulse therapy within three months of enrollment -Patients whose steroid dosage was modified within three months of enrollment (4)20 years of age or older when giving informed consent (5)Detectable HTLV-1 proviral load in peripheral blood (6)No change in OSAME motor disability score for three months or more before enrollment (7)Capable of walking at least 10meters(regardless of whether a walking aid is used or not) at the time when informed consent is obtained (8)Available for hospitalization through one week after KW-0761treatment (9)Primary organ functions are stable(according to the latest laboratory results from within a maximum of 28 days before enrollment) -Neutrophil count:>=1,500/mm3 -Platelets:>=100,000/mm3 -Hemoglobin:>=9.0g/dL -AST(GOT),ALT(GPT),Total bilirubin,Serum creatinine:=<1.5X established normal upper limit -EKG:Abnormality requiring treatment is not found -LVEF:>=50% -SpO2:>=90% (10)The patient truly consents to participate in the study of his or her own free will PhaseIIa (1)The stability of the patient after receiving treatment is confirmed during PhaseI (2)Patients are available for hospitalization following KW-0761treatment (3)The patient gives of his/her own free will consent to move forward to PhaseIIa
Exclusion criteria
Exclusion criteria: PhaseI (1)Patients with a history of acute or chronic hepatitis or hepatic cirrhosis (2)Patients with a history of tuberculosis or with active tuberculosis (3)Patients who have developed a myocardial infarction within 12months of enrollment (4)Patients with a history of allergic reaction to antibody-based treatments (5)Patients who have taken immunosuppressant drugs or interferon-a within 6months of enrollment (6)Patients who have undergone live or attenuated/inactivated vaccinations within 4weeks of enrollment, or who plan to be vaccinated during the course of the study (7)Patients with serious complicating conditions (8)Patients with any ailment that could be exacerbated by the administration of KW-0761 (9)Patients with a history of cancer with complications. However, the following patients are not excluded: -Patients with radically resected solid tumor which have not recurred within the 5years preceding enrollment -Patients with radically resected basal cell carcinoma of the skin, squamous cell carcinoma (except malignant melanoma),non-invasive cervix carcinoma, and carcinoma in situ in the gastrointestinal tract or corpus of the uterus even if recurrence has occurred within 5years of enrollment (10)Patients with ALT (11)Patients who are pregnant, breastfeeding, or may become pregnant (12)Patients taking multivitamins(Alinamin,vitaminC etc.) or supplements such as fucoidan, catechin, or pentosan polysulfate within 2weeks of enrollment (13)Patients who have taken other experimental drugs within 4months of giving informed consent (14)Patients with spinal cord compression lesion complications (15)Patients with mental disabilities, epilepsy, or dementia (16)HBsAg-, anti-HBc- or HBV-DNA-positive (as measured using real-time PCR) (17)HCV antibody-positive (18)HIV antibody-positive (19)Patients considered unqualified to join the study by the investigators PhaseIIa (1)Patients who meet the exclusion criteria for PhaseI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| -Safety: Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), Presence or absence and nature of any adverse effects,and Number of patients expressing the anti-KW-0761 neutralizing antibody -Pharmacokinetics: The concentration in the plasma and cerebrospinal fluid of KW-0761 after a single dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| -Efficacy: PhaseI Effectiveness against infected cells (HTLV-1 proviral load in the peripheral blood). PhaseIIa The duration of the effectiveness against infected cells (where effective is defined as a drop to 40% or less the peripheral blood HTLV-1 proviral load before treatment with KW-0761 during PhaseI.) Lack of decline in performance during the 10-meter timed walk.(An increase in time compared to before the KW-0761 treatment is defined as disease progression.) | — |
Countries
Japan
Contacts
Public ContactEriko Aotani, RN, MSN, CCRP
0761HAM Coordinationg Center Kanagawa Academy of Science and Technology Global Health Research Coordinating Center
Outcome results
None listed