A Study of KW-0761 in Subjects With HTLV-1 Associated Myelopathy (HAM)

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)

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.

Study Overview

• Status: Terminated
• Conditions: HTLV-1 Associated Myelopathy
• Intervention / Treatment: Drug: KW-0761 0.3 mg/kg IV; Drug: Placebo (saline)

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).

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan
    • University Hosipital, Kyoto Prefectural University of Medicine
  • Aichi
    • Nagoya, Aichi, Japan
      • Nagoya University Hosipital
  • Ehime
    • Tone, Ehime, Japan
      • Ehime University Hospital
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan
      • Hospital of the University of Occupational and Environmental Health, Japan
  • Fukuoka Prefecture
    • Fukuoka, Fukuoka Prefecture, Japan
      • Fukuoka University Hospital
    • Fukuoka, Fukuoka Prefecture, Japan
      • Kyushu University Hospital
  • Kagoshima Prefecture
    • Kagoshima, Kagoshima Prefecture, Japan
      • Kagoshima City Hospital
    • Kagoshima, Kagoshima Prefecture, Japan
      • Kagoshima University Hospital
  • Kanagawa Prefecture
    • Kawasaki, Kanagawa Prefecture, Japan
      • St. Marianna University School of Medicine Hospital
  • Kumamoto Prefecture
    • Kumamoto, Kumamoto Prefecture, Japan
      • Kumamoto University Hospital
  • Miyagi Prefecture
    • Sendai, Miyagi Prefecture, Japan
      • Tohoku University Hosipital
  • Miyazaki
    • Miyakonojō, Miyazaki, Japan
      • Fujimoto General Hospital
  • Oita Prefecture
    • Oita, Oita Prefecture, Japan
      • Oita Prefectural Hospital
  • Okinawa Prefecture
    • Ginowan, Okinawa Prefecture, Japan
      • National Hospital Organization Okinawa National Hospital
    • Nakagami, Okinawa Prefecture, Japan
      • University of the Ryukyus Hospital
  • Osaka Prefecture
    • Hirakata, Osaka Prefecture, Japan
      • Kansai Medical University Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: KW-0761 0.3 mg/kg IV; Intravenous injection every 12 weeks.
Placebo Comparator: 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.	Drug: Placebo (saline); Intravenous injection every 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in Osame's motor disability score	At week 4, 8 and 12 after second injection

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Modified Ashworth Scale	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 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
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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2017
• Primary Completion (Actual): June 6, 2019
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (Actual): June 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Retroviridae Infections; Hematologic Diseases; Central Nervous System Infections; Myelitis; Deltaretrovirus Infections; HTLV-I Infections; Spinal Cord Diseases; Bone Marrow Diseases; Paraparesis, Tropical Spastic; Antineoplastic Agents; Mogamulizumab
• Other Study ID Numbers: 0761HAM-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No