UMIN-CTR Clinical Trial

Public title

Phase IIb clinical trial of steroid therapy in patients with HAM(Slow progressor)

Acronym

HAMLET-P

Scientific Title

Phase IIb clinical trial of steroid therapy in patients with HAM(Slow progressor)

Scientific Title:Acronym

HAMLET-P

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 evaluate the efficacy and safety of prednisolone therapy in patients with slow progressing HAM

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II,III

Primary outcomes

Efficacy:
Change in walking time as measured by 10-meter walk test from baseline to Day 169 (Week 24)

Key secondary outcomes

Efficacy:
<Prednisolone group versus control group>
-Walking time measured by 10-meter walk test
Change in the time from baseline to Day 29 (Week 4) and Day 85 (Week 12)
-Distances walked over two minutes as well as six minutes
Change in the distances from baseline to Day 29 (Week 4), Day 85 (Week 12) and Day 169 (Week 24)
- Cerebrospinal fluid neopterin concentration
Change in the concentration from baseline to Day 169 (Week 24)
-Discontinuation rate of the study drug during the period of treatment with the study drug (Day 1 to Day 169 [Week 24])
<Comparison in the control group>
Walk tests (Walking time in 10-meter walk test and distances walked over two and six minutes)
Comparison of changes in the results from baseline to Day 169 (Week 24) with those from Day 169 (Week 24) to Day 337 (Week 48)
-Cerebrospinal fluid neopterin concentration
Comparison of change in the concentration from baseline to Day 169 (Week 24) with that from Day 169 (Week 24) to Day 337 (Week 48)
-Safety
Adverse event (incidence and severity)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Prednisolone is orally administered at a maximum dose of 0.5mg/kg/day and then tapered to a maintenance dose of 5mg/day.

Interventions/Control_2

Indistinguishable placebo is orally administered for 24 weeks, and then 5mg/day of prednisolone for the next 24 weeks.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Patients diagnosed with HAM by reference to the Belem criteria (2006).
(2) Patients must have signed an informed consent form at age 18 or older
(3) Patients who can walk 10 meters or longer regardless of walking aid use at the time of informed consent. Note, however, that the number of walking stick is not allowed to exceed two and wheeled walker may be used.
(4) Patients in whom function of the major organ systems is maintained. (To be confirmed by the most recent laboratory data within 28 days prior to enrollment)
1. Neutrophils: 1500/mm3 or more
2. PLT: 100,000/mm3 or more
3. Hb : 9.0 g/dL or more
4. AST: three times the upper limit of the institutional reference value or lower
5. ALT: three times the upper limit of the institutional reference value or lower
6. Serum creatinine: one and a half times the upper limit of the institutional reference value or lower
7. HbA1c: 6.5 percent or less
(5) Patients or their legal guardians must voluntarily give written informed consent to participate in the study
(6) Patients who are able and willing to visit the hospitals in line with the study schedule to receive treatment and for follow-up

Key exclusion criteria

(2)Patients defined as slow or non-progressor who have received corticosteroids or other treatment targeted to HAM within 48 weeks prior to giving informed consent
(3)Patients who have undergone invasive surgeries requiring general anesthesia within 24 weeks prior to giving informed consent
(4)Patients who have participated in other treatment studies within 16 weeks prior to giving informed consent
(5)Patients who have received live or attenuated/inactivated vaccines within four weeks prior to giving informed consent or plan to receive those during the study period
(6)Patients who have received 1.5g/day or more of ascorbic acid, prosultiamine, or pentosan polysulfate within two weeks prior to giving informed consent
(7)Patients with a history of acute myocardial infarction
(8)Patients with a history of tuberculosis or with active tuberculosis
(9)Patients with serious complications
(10)Patients with uncontrolled hypertension
(11)Patients with uncontrolled electrolyte imbalance
(12)Patients with thrombosis
(13)Patients with cancer or a history of cancer
(14)Patients with peptic ulcer
(15)Patients with ATL
(16)Patients with poorly controlled eye disease
(17)Patients with a history of steroid-induced glaucoma
(18)Pregnant or breastfeeding women or patients who may become pregnant or withhold assent to prevention of conception by taking appropriate approach such as condom in cooperation with their partners during the study period
(19)Patients with compressive spinal cord lesions such as osteoarthritis of the spine, ossification of posterior longitudinal ligament and ossification of yellow ligament, or joint diseases such as rheumatoid arthritis and osteoarthritis, which preclude assessment using the walk tests or can be worsened by the walk tests
(20)Patients with neurological deficits or findings on MRI suggesting it due to disorders other than HAM

Target sample size

40

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	Ushitani,Kuwahara

Organization

HAMLET-P Coordinating Center

Division name

Clinical Research Data Center,St. Marianna University School of Medicine

Zip code

Address

2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511 Japan

TEL

044-977-8111(6191)

Homepage URL

Email

mariadc_ham@marianna-u.ac.jp

Institute

St. Marianna University School of Medicine Hospital

Institute

Department

Personal name

Organization

The Research on Measures for Intractable Diseases Project of Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

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

2016/07/27

Institutions

聖マリアンナ医科大学病院（神奈川県）

Date of disclosure of the study information

2016

Year

09

Month

20

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

2016

Year

08

Month

03

Day

Date of IRB

2016

Year

08

Month

19

Day

Anticipated trial start date

2016

Year

09

Month

16

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

09

Month

16

Day

Last modified on

2021

Year

04

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027727