UMIN-CTR Clinical Trial

Public title

Phase I&IIa trial of KW-0761 in patients with HAM

Acronym

0761HAM

Scientific Title

Phase I&IIa trial of KW-0761 in patients with HAM

Scientific Title:Acronym

0761HAM

Region

Japan

Condition

HTLV-1-Associated-Myelopathy Tropical Spastic Paraparesis (HAM/TSP)

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To study the pharmacokinetics of KW-0761 and clarify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT) for HAM/TSP patients.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

-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.

Key secondary outcomes

-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.)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

KW-0761 IV administration

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key 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

Key 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

Target sample size

33

Name of lead principal investigator

1st name
Middle name
Last name	Yoshihisa Yamano M.D.,Ph.D.

Organization

St. Marianna University School of Medicine Hospital

Division name

Department of Neurology

Zip code

Address

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8512 Japan

TEL

044-977-8111

Email

yyamano@marianna-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Eriko Aotani, RN, MSN, CCRP

Organization

0761HAM Coordinationg Center

Division name

Kanagawa Academy of Science and Technology Global Health Research Coordinating Center

Zip code

Address

KSP EAST 3F. 3-2-1 SAKADO. TAKATSU-KU. KAWASAKI-SHI. KANAGAWA 213-0012. JAPAN

TEL

044-850-1731

Homepage URL

Email

ham-japan@newkast.or.jp

Institute

St. Marianna University School of Medicine Hospital

Institute

Department

Personal name

Organization

The Research on Measures for Intractable Diseases Project of the Ministry of Health, Labour, and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

2013/11/12, 6回

Institutions

聖マリアンナ医科大学附属病院（神奈川県）

Date of disclosure of the study information

2013

Year

12

Month

23

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

09

Month

03

Day

Date of IRB

Anticipated trial start date

2014

Year

01

Month

10

Day

Last follow-up date

2016

Year

01

Month

31

Day

Date of closure to data entry

2016

Year

02

Month

29

Day

Date trial data considered complete

2016

Year

04

Month

30

Day

Date analysis concluded

2016

Year

06

Month

30

Day

Other related information

Registered date

2013

Year

12

Month

23

Day

Last modified on

2016

Year

03

Month

17

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014800