RecruitingNCT07294144Updated Jun 25, 2026

Tofersen in Non-SOD1 ALS

A Phase 2 interventional study of Tofersen in ALS (Amyotrophic Lateral Sclerosis), sponsored by Washington University School of Medicine. Recruiting at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-25.

Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment

From the registry’s dates

Started Dec 2025; still recruiting 9 months later.

Phase: Phase 2
Study type: Interventional
Enrollment: 30
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

The goal of this clinical trial is to evaluate whether tofersen is safe and effective in adults with non-SOD1 ALS. Tofersen is currently approved by the U.S. Food and Drug Administration to treat SOD1-ALS. The main questions it aims to answer are:

Does tofersen lower the levels of neurofilament light chain (NfL) in the blood and CSF of adult participants with non-SOD1 ALS?
Is tofersen safe and tolerable for adult participants with non-SOD1 ALS?
Does tofersen affect other measurements such as clinical outcomes and quality-of-life measures in participants with non-SOD1 ALS?

Participants will :

Receive 100mg tofersen via lumbar puncture for 24 weeks. The doses are at the following time points: Weeks 0, 2, 4, 8, 12, 16, 20, and 24.
Complete 2 follow-up visits following the end of the dosing period at Weeks 28 and 32.
Complete a variety of questionnaires and outcome measurements such as strength and breathing testing.

Conditions studied

ALS (Amyotrophic Lateral Sclerosis)

Browse trials for

Amyotrophic Lateral Sclerosis 981

Keywords

als
amyotrophic lateral sclerosis
tofersen
qalsody

In context

Amyotrophic Lateral Sclerosis

981 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 283 are open to participants now.

This study's planned enrollment of 30 is below the median of 36 across 667 interventional studies indexed under Amyotrophic Lateral Sclerosis.

Browse Amyotrophic Lateral Sclerosis studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local participant privacy regulations.
Aged 18 years or older at the time of informed consent.
Confirmed diagnosis of ALS.
Time since onset of weakness due to ALS ≤ 24 months at the time of the screening visit.
Prior confirmed genetic testing negative for SOD1 and FUS mutations. Participants with mutations in genes other than SOD1 and FUS may be enrolled at the discretion of the Site Investigator.
SVC ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
Medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
All participants must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
If taking riluzole, participant must be on a stable dose for ≥ 30 days prior to Day 1 and expected to remain at that dose until the final study visit.
If taking edaravone, participant must have initiated edaravone ≥ 60 days (2 treatment cycles) prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study.

Exclusion criteria

Exclusion Criteria:

Treatment with another investigational drug (including investigational drugs for ALS through compassionate use or expanded access programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
Current enrollment in any other interventional study.
History of drug abuse or alcoholism within ≤ 6 months of study enrollment that would limit participation in the study, as determined by the Investigator.
Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.
Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that according to the Investigator would interfere with the conduct or assessments of the study.
History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in neurofilament, in the opinion of the Investigator.
Female participants who are pregnant or currently breastfeeding.
Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days, as determined by the Investigator.
History of allergies to a broad range of anesthetics.
Tracheostomy.
Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication that cannot be safely held before and/or after an LP procedure according to local or institutional guidelines and/or Investigator determination.
Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment.
Inability to comply with study requirements.
Other unspecified reasons that, in the opinion of the Investigator, make the participant unsuitable for enrollment.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 30 participants (estimated)

Study arms

Experimental
Tofersen
Drug: Tofersen

Interventions

DrugTofersen
Tofersen 100 mg administered intrathecally.

What researchers measure

Primary outcomes

Proportion of participants with ≥30% reduction in plasma NfL
Time frame: From Baseline to Week 28

Secondary outcomes

Proportion of participants with ≥ 30% reduction in CSF NfL
Time frame: From Baseline to Week 28
Change in plasma and CSF NfL levels
Time frame: From Baseline to Week 28
Incidence of adverse events and serious adverse events
Time frame: From Baseline through study completion, an average of 8 months

Other outcomes

Changes in CSF SOD1
Time frame: From Baseline to Week 28
Change in ALS Functional Rating Scale - Revised (ALSFRS-R)
The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.
Time frame: From Baseline to Week 28
Change in Slow Vital Capacity (SVC)
Vital capacity will be measured by means of a slow vital capacity test, performed following a standardized protocol established by the Northeast ALS Consortium.
Time frame: From Baseline to Week 28
Change in Handheld Dynamometry (HHD)
Quantitative muscle strength will be evaluated using HHD of multiple muscles using standard participant positioning.
Time frame: From Baseline to Week 28
Change in Rasch Overall ALS Disability Scale (ROADS)
The Rasch-built Overall ALS Disability Scale (ROADS) is a patient-reported outcome measure that assesses 28 items, each scored 0-2, and then provides a normed total score from 0-146 to capture overall disability level in a linearly-weighted manner, meaning that a 1-point change on the normed ROADS score represents a quantifiable and consistent measurement of disability, and a 2-point change reflects twice the amount of disability.
Time frame: From Baseline to Week 28
Change in Motor Functional Independence Measure (FIM)
The Motor Functional Independence Measure (FIM) consists of 13 items assessing motor function scored 0-7, for a maximum score of 91, which indicates the highest level of function.
Time frame: From Baseline to Week 28
Change in EuroQol 5-dimension, 5-level scale (EQ-5D-5L)
The EuroQol Five Dimension (EQ-5D-5L) is a standardized generic measure of health status and consists of 2 sections. The first section comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D-5L measures the dimensions on a 5-point scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The second section comprises the visual analogue scale that records the respondent's self-rated health on a vertical scale ranging from 0 to 100 where the endpoints are labelled "best imaginable health state" and "worst imaginable health state."
Time frame: From Baseline to Week 28
Change in ALS Assessment Questionnaire, 5-item scale (ALSAQ-5)
The ALSAQ-5 is a disease-specific self-reported health status questionnaire. The ALSAQ-5 contains 5 questions, each corresponding to 1 of the following 5 health-related dimensions: physical mobility, activities of daily living, eating and drinking abilities, communication, and emotional functioning. The questions are followed by 5 responses with the raw scores ranging from 0 = Never to 4 = Always or cannot do at all. The ALSAQ-5 total score ranges from 0 to 100 with a lower score representing a better health-related status.
Time frame: From Baseline to Week 28

Study locations

3 of 3 sites recruiting

Emory University
Atlanta, Georgia 30322, United States
- Karon Simmons · Contact · kmsimm2@emory.edu · 404-712-4182
- Jonathan Glass, MD · Principal investigator
Recruiting
Massachusetts General Hospital
Boston, Massachusetts 02114, United States
- Miranda Durcan · Contact · tofersensporadichealey@mgb.org · 617-643-9550
- Suma Babu, MBBS, MPH · Principal investigator
Recruiting
Washington University ALS Center
St Louis, Missouri 63110, United States
- ALS Clinical Research Team · Contact · als@wustl.edu · 1-844-257-2273
- Timothy M Miller, MD, PhD · Principal investigator
Recruiting

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 25, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT07294144
Lead sponsor: Washington University School of Medicine
Collaborators: Biogen
Responsible party: Timothy M. Miller, MD, PhD (David Clayson Professor of Neurology, Washington University School of Medicine) — Principal investigator
First posted: Dec 19, 2025
Start date: Dec 29, 2025
Primary completion: Jan 2027 (estimated)
Completion: May 2028 (estimated)
Last update: Jun 25, 2026

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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