Tofersen in Non-SOD1 ALS

ConditionALS (Amyotrophic Lateral Sclerosis)

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorWashington University School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

Tofersen
Drug
Tofersen 100 mg administered intrathecally.

Treatment groups

30 Participants

are divided into 1 treatment group

Group A: TofersenExperimental treatment 1 intervention

Trial outcomes

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