UMIN-ICDS Clinical Trial

Public title

Impact of Tofersen treatment on Neurofilament light chain level in Japanese patients with SOD1-ALS

Acronym

Impact of Tofersen treatment on Neurofilament light chain level in Japanese patients with SOD1-ALS

Scientific Title

Impact of Tofersen treatment on Neurofilament light chain level in Japanese patients with SOD1-ALS

Scientific Title:Acronym

Impact of Tofersen treatment on Neurofilament light chain level in Japanese patients with SOD1-ALS

Region

Japan

Condition

Patients with SOD1-ALS

Classification by specialty

Neurology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

To investigate the effects of tofersen treatment on neurofilament light chain levels and clinical outcomes in Japanese patients with SOD1-ALS.

Basic objectives2

Others

Basic objectives -Others

Observational study

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

Change of NfL concentration in CSF at Week 24 after Tofersen initiation from baseline (LS geometric mean ratio to baseline)

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

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

15

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients who meet all of the following criteria will be eligible for participation in this study:
(1)Patients aged 15 years or older at the time of obtaining informed consent.
(2)Patients diagnosed with superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS) based on genetic testing.
(3)Patients who are receiving treatment with tofersen under routine clinical practice, including those who have discontinued tofersen at the time of informed consent.
(4)Patients capable of providing written informed consent.
-Patients who are able to understand the purpose and potential risks of the study and from whom written informed consent can be obtained in accordance with national and local personal data protection laws.
-For patients aged 15 years or older and under 18 years at the time of consent, written informed consent must be obtained from both the patient and an appropriate legally authorized representative.
-If a patient has sufficient decision-making capacity but has difficulty writing due to progression of the underlying disease or other reasons, written informed consent may be obtained by proxy writing, provided that the patient's intention to participate in the study is confirmed and the consent process is conducted in the presence of an impartial witness.
(5)Patients who are able to provide cerebrospinal fluid (CSF) as their own biological specimens for this observational study, including blood samples when feasible.

Key exclusion criteria

Patients who meet any of the following criteria will be excluded from the study:
(1)Patients with medical or psychiatric conditions that may interfere with their ability to comply with study procedures or assessments.
(2)Patients who have previously received ALS treatments with expected long-lasting or sustained effects, such as viral gene therapies.
(3)Patients with comorbid conditions known to be associated with elevated neurofilament light chain (NfL)levels, including multiple sclerosis, dementia, Parkinson's disease or other neurodegenerative diseases, traumatic brain injury, or stroke.
(4)Patients who are currently participating in, or have previously participated in, other clinical trials of tofersen, including the VALOR trial and its extension study, or the ATLAS trial.
Expanded access programs and compassionate use programs are not considered clinical trials.
(5)Patients who are currently participating in, or are planning to participate in, another clinical trial for amyotrophic lateral sclerosis (ALS).
(6)Patients who are deemed inappropriate for participation in this observational study by the principal investigator or sub-investigators.

Target sample size

40

Name of lead principal investigator

1st name	Masashi
Middle name
Last name	Aoki

Organization

Tohoku University School of Medicine

Division name

Department of Neurology

Zip code

980-8574

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi

TEL

022-717-7000

Email

masashi.aoki.c8@tohoku.ac.jp

Name of contact person

1st name	Rie
Middle name
Last name	Yokokawa

Organization

EPS Corporation

Division name

Clinical Research Center, RWE Division

Zip code

564-0063

Address

4th Floor, Maruito Daini Esaka Building 1-17-6 Esaka-cho, Suita-shi, Osaka

TEL

06-7176-5731

Homepage URL

Email

prj-tof-office@eps.co.jp

Institute

Tohoku University School of Medicine

Institute

Department

Personal name

Organization

Biogen Japan Ltd.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Research Ethics Committee of Nihonbashi Sakura Clinic

Address

5F, Inamura Building, 1-9-2 Nihonbashikayabacho, Chuo-ku, Tokyo 103-0025, Japan

Tel

03-6661-9061

Email

c-irb_ug@neues.co.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東北大学病院（宮城県）、岐阜大学医学部附属病院（岐阜県）、地方独立行政法人東京都立病院機構　東京都立神経病院（東京都）、滋賀医科大学医学部附属病院（滋賀県）、九州大学病院（福岡県）、高知大学医学部附属病院（高知県）大阪大学医学部附属病院（大阪府）、名古屋大学医学部附属病院（愛知県）、東京科学大学病院（東京都）、東邦大学医療センター大森病院（東京都）、国立研究開発法人 国立精神・神経医療研究センター（東京都）、東京大学医学部附属病院（東京都）、奈良県立医科大学〈奈良県立医科大学附属病院〉（奈良県）、岡山赤十字病院（岡山県）、愛知医科大学病院（愛知県）

Date of disclosure of the study information

2026

Year

07

Month

08

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

Open public recruiting

Date of protocol fixation

2026

Year

03

Month

10

Day

Date of IRB

2026

Year

03

Month

18

Day

Anticipated trial start date

2026

Year

07

Month

08

Day

Last follow-up date

2027

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

ALS is a progressive neurodegenerative disease, and mutations in the SOD1 gene represent one of the major causes of familial ALS. In the Japanese population, the proportion of familial ALS patients with SOD1 mutations is known to be relatively high.
Tofersen is an antisense oligonucleotide therapy that suppresses the synthesis of SOD1 protein. In overseas clinical trials, including the VALOR trial, although a statistically significant improvement in the primary clinical endpoint, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), was not demonstrated, a reduction in neurofilament light chain (NfL), a biomarker of disease activity, was reported. However, the number of Japanese patients included in these studies was limited, and the accumulation of additional data on the efficacy and safety of tofersen in Japanese patients is required.
In this study, Japanese patients with SOD1-ALS who are receiving tofersen treatment as part of routine clinical care will be enrolled. Longitudinal changes in NfL concentrations in cerebrospinal fluid and blood, SOD1 protein concentrations, and clinical parameters (including ALSFRS-R, respiratory function, muscle strength, and body weight) before and after initiation of tofersen treatment will be collected and analyzed.
In addition, treatment responses in patients with slowly progressive SOD1 variants or variants of uncertain significance (VUS) will be explored.
Because it is difficult to assess the therapeutic effects of tofersen based solely on clinical symptoms, this study aims to generate evidence to support clinical decision-making for SOD1-ALS treatment in Japan by collecting real-world data that integrate biomarker measurements with clinical outcomes.

Registered date

2026

Year

07

Month

08

Day

Last modified on

2026

Year

07

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000069802