UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000033504
Receipt number	R000038203
Scientific Title	An uncontrolled open-label study on the efficacy and safety of sirolimus for epileptic seizures associated with focal cortical dysplasia type-II
Date of disclosure of the study information	2018/07/25
Last modified on	2021/08/11 14:37:47

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Basic information

Public title

An uncontrolled open-label study on the efficacy and safety of sirolimus for epileptic seizures associated with focal cortical dysplasia type-II

Acronym

An investigator-initiated clinical trial on the efficacy and safety of sirolimus for epileptic seizures associated with FCD type-II

Scientific Title

An uncontrolled open-label study on the efficacy and safety of sirolimus for epileptic seizures associated with focal cortical dysplasia type-II

Scientific Title:Acronym

An investigator-initiated clinical trial on the efficacy and safety of sirolimus for epileptic seizures associated with FCD type-II

Region

Japan

Condition

focal cortical dysplasia (type-II)

Classification by specialty

Neurology Pediatrics

Classification by malignancy

Others

Genomic information

Objectives

Narrative objectives1

To assess the efficacy, safety, and pharmacokinetics of sirolimus against epileptic seizures in focal cortical dysplasia type-II

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Assessment

Primary outcomes

A reduction rate of incidence of partial seizures (including secondarily generalized seizures) per 28 days during maintenance therapy from the observation period

Key secondary outcomes

- Change in incidence of general seizures per 28 days during maintenance therapy from the observation period
- Change in incidence epileptic spasm per 28 days during maintenance therapy from the observation period
- Change in incidence of heavy-weight attacks per 28 days during maintenance period from the observation period
- A response rate (proportion of cases in which incidence of seizures during maintenance therapy decreased by 50% or more from the observation period)
- Proportion of resolution of partial seizures during maintenance therapy
- A decrease rate and a response rate of incidence of partial seizures at 4 weeks, 8 weeks, and 12 weeks in the maintenance therapy from the observation period
- Adverse events

Base

Study type

Interventional

Study design

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Institution is not considered as adjustment factor.

Blocking

Concealment

No need to know

Intervention

No. of arms

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

The investigational drug (sirolimus) is orally administered once a day with the following doses:
<Dose adjustment period>
Initial amount: 1 mg/day for body weight of less than 40 kg, and 2 mg/day for 40 kg or more.
Dose adjustment: to increase as necessary to adjust the trough concentration of sirolimus to the range of 5-15 ng/ml, and then, to shift to the maintenance therapy period.
<Maintenance therapy period>
To adopt dosage regimen and dose of sirolimus at trough concentration of 5-15 ng/ml.

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

Eligibility

Age-lower limit

6 years-old <=

Age-upper limit

65 years-old >=

Gender

Male and Female

Key inclusion criteria

1. Diagnosed with pathologically localized cortical dysplasia type-II by neuroimaging findings in head MRI within 156 weeks prior to enrollment or brain pathology examination before enrollment.
2. Aged 6 to 65 years at the time of informed consent.
3. Diagnosed with a partial seizure (a simple partial seizure with motor signs which can be objectively diagnosed, a complex partial seizure, or a secondarily generalized seizure) based on the 1981 epileptic seizure type international classification of the International League Against Epilepsy (ILAE).
4. Having treated for at least 52 weeks with two or more antiepileptic drugs after diagnosis with epilepsy.
5. Under treatment with 1 to 4 antiepileptic drugs.
6. Whose dose and regimen of antiepileptic drug are constant from the 8th week before enrollment, or whose stimulation condition is constant from the 8th week before enrollment in case of performing vagus nerve stimulation therapy.
7. With two or more partial seizures (including secondarily generalized seizures) during the baseline observation period of 28 days.
8. Provided written consent by themselves/parent or legal representatives.

Key exclusion criteria

1. Those participated in other trials within 12 weeks before the time of consent.
2. Having used sirolimus or everolimus within 52 weeks before enrollment.
3. Who cannot accurately record the number and time of epileptic seizures by themselves/representatives.
4. Suspected of progressive lesions in CT or MRI.
5. Having underwent cerebral surgery for epilepsy within 28 weeks prior to enrollment.
6. Taking Felbamate or Vigabatrine or having taken it within 28 weeks before enrollment.
7. Under ketogenic diet therapy.
8. Having suicide attempts in the past.
9. With a history or complications of substance abuse including alcohol abuse.
10. Those possibly pregnant and cannot perform contraception during the study period (including partners), pregnant or lactating.
11. Falling under any of the following in clinical examination during baseline observation period:
- At least 2.5 times the reference value of AST or ALT
- WBC count of less than 3,000/micro L, Ht of less than 30%, platelets of less than 80,000/micro L, or neutrophil counts of less than 1,000/ micro L
- C_cr of less than 50 ml/min
- HBs antigen-positive, HBs antibody-positive except after vaccination with hepatitis B vaccine, or HBc antibody-positive. Or active hepatitis C excluding inactive cases with normal liver function.
- In poor control of dyslipidemia with serum triglycerides of 500 mg/dL or more, or LDL cholesterol of 190 mg/dL or more despite being treated for dyslipidaemia.
- With renal dysfunction. (eGFR of less than 30 ml/min/1.73 m²)
12. With complications of arrhythmia requiring treatment.
13. With complications of heart/renal failure that may affect hemodynamics.
14. With immunodeficiency complications.
15. Having underwent surgery (surgery requiring invasion into a body cavity or surgery requiring suture of three or more needles including biopsy) within 12 weeks before enrollment.
16. Judged inappropriate for participating in this study by the principal investigator/sub-investigators.

Target sample size

Research contact person

Name of lead principal investigator

1st name Mitsuhiro

Middle name

Last name Kato

Organization

Showa University Hospital

Division name

Pediatrics

Zip code

142-8555

Address

1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

TEL

03-3784-8000

Email

ktmt-hro@umin.ac.jp

Public contact

Name of contact person

1st name Kenji

Middle name

Last name Nagaya

Organization

National Hospital Organization Nagoya Medical Center

Division name

Department of Clinical Research Planning and Management, Clinical Research Center

Zip code

460-0001

Address

4-1-1 Sannomaru, Naka-ku, Nagoya, Aichi 460-0001, Japan

TEL

052-951-1111

Homepage URL

Email

study.office@nnh.go.jp

Sponsor or person

Institute

Hokkaido University Hospital
Nishi-Niigata Chuo National Hospital
National Center Hospital, NCNP
Shizuoka Institute of Epilepsy and Neurological Disorders
Okayama University Hospital

Institute

Department

Personal name

Funding Source

Organization

AMED

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Japan

Other related organizations

Co-sponsor

Name of secondary funder(s)

IRB Contact (For public release)

Organization

NHO Shizuoka Institute of Epilepsy and Neurological Disorders

Address

Urushiyama 886, Aoi-ku, Shizuoka 420-8688, Japan

Tel

054-245-5680

Email

yamamoty@shizuokamind.org

Secondary IDs

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

北海道大学病院(北海道)
国立病院機構西新潟中央病院(新潟県)
国立精神・神経医療研究センター病院(東京都)
国立病院機構静岡てんかん・神経医療センター(静岡県)
岡山大学病院(岡山県)

Other administrative information

Date of disclosure of the study information

2018 Year 07 Month 25 Day

Related information

URL releasing protocol

Publication of results

Unpublished

Result

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

Progress

Recruitment status

Completed

Date of protocol fixation

2018 Year 07 Month 13 Day

Date of IRB

2018 Year 08 Month 24 Day

Anticipated trial start date

2018 Year 10 Month 01 Day

Last follow-up date

2020 Year 09 Month 30 Day

Date of closure to data entry

2020 Year 10 Month 30 Day

Date trial data considered complete

2020 Year 12 Month 15 Day

Date analysis concluded

2021 Year 03 Month 12 Day

Other

Other related information

Management information

Registered date

2018 Year 07 Month 25 Day

Last modified on

2021 Year 08 Month 11 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038203