Tofersen in Non-SOD1 ALS

Overview

Official title

A Study to Evaluate the Biological Effect of Tofersen in Adults With Amyotrophic Lateral Sclerosis Without Mutations in SOD1

Brief title

Tofersen in Non-SOD1 ALS

Registration type

ClinicalTrials.gov

NCT number

NCT07294144

Status

Recruiting

Study category

Interventional, Drug trial, Biomarker, Genetic, Biospecimen

Sponsor / center

Washington University School of Medicine

Research center

Emory ALS Center

Collaborators

Biogen

Study type

Interventional study

Phase

Phase 2

Enrollment

30

Start date

12-29-2025

Primary completion date

01-XX-2027

Estimated / actual completion date

05-XX-2028

Last source update

06-25-2026

What is being studied?

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.

Intervention(s)

Center-specific eligibility information

Emory lists lumbar punctures, vital capacity greater than 50%, disease onset fewer than 24 months before screening, no blood thinners, and no SOD1 or FUS mutation.

Who may be eligible?

This is a simplified summary. The official study team or research center determines eligibility.

Population / disease status

Diagnosed ALS

Diagnosis / conditions

ALS (Amyotrophic Lateral Sclerosis)

Age

18 Years to Not stated in the official study record.

Disease duration

≤ 24 months

Respiratory criteria

Not stated in the official study record.

ALSFRS-R criteria

Not stated in the official study record.

Genetic criteria

The official eligibility criteria include language relevant to this topic; review the full criteria below.

Medication requirements

The official eligibility criteria include language relevant to this topic; review the full criteria below.

Major inclusion and exclusion criteria from the official record

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:

* 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.

Genetics

Gene-specific study?

Yes

Gene or variant

SOD1

Genetic test required?

Not stated in the official study record.

Known carrier required?

Not stated

Confirmed pathogenic variant required?

Not stated in the official study record.

Presymptomatic carriers eligible?

Not stated in the official study record.

At-risk relative eligible?

Not stated

Genetic test provided?

Not stated in the official study record.

Genetic counseling provided?

Not stated in the official study record.

Results returned / offered?

Not stated

Family history required?

Not stated in the official study record.

Study design

Randomized?

Not stated in the official study record.

Allocation

Not stated in the official study record.

Intervention model

Not stated in the official study record.

Masking

Not stated in the official study record.

Placebo

Not stated in the official study record.

Primary purpose

Not stated in the official study record.

Endpoints

Primary outcome measures

• Proportion of participants with ≥30% reduction in plasma NfL

Secondary outcome measures

• Proportion of participants with ≥ 30% reduction in CSF NfL
• Change in plasma and CSF NfL levels
• Incidence of adverse events and serious adverse events

A biomarker outcome should not automatically be interpreted as a clinical outcome.

Locations

Contact

Research-center contact: Karon Simmons · kmsimm2@emory.edu

Central contact: Not stated in the official study record.