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

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

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.

Study Overview

• Status: Unknown
• Conditions: HTLV-I-Associated Myelopathy
• Intervention / Treatment: Drug: Tamibarotene

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kanagawa, Japan, 243-0402
    • Iseikai Medical Corporation, Shoyo Kashiwadai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: St. Marianna University School of Medicine
• Investigators: Principal Investigator: Yoshihisa Yamano, MD, St. Marianna University School of Medicine

Publications and helpful links

Helpful Links

• HTLV-1 Information for Japanese

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Anticipated): March 1, 2012
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: April 25, 2011
• First Submitted That Met QC Criteria: April 26, 2011
• First Posted (Estimate): April 28, 2011

Study Record Updates

• Last Update Posted (Estimate): July 22, 2011
• Last Update Submitted That Met QC Criteria: July 21, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Tropical Spastic Paraparesis; HAM; TSP
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Retroviridae Infections; Neurologic Manifestations; Hematologic Diseases; Musculoskeletal Diseases; Muscular Diseases; Central Nervous System Infections; Neuromuscular Manifestations; Muscle Hypertonia; Paresis; Myelitis; Deltaretrovirus Infections; HTLV-I Infections; Spinal Cord Diseases; Bone Marrow Diseases; Muscle Spasticity; Paraparesis, Tropical Spastic; Paraparesis; Paraparesis, Spastic
• Other Study ID Numbers: AM80H-01