Study of Tofersen for Adults with Presymptomatic Amyotrophic Lateral Sclerosis (ALS) Due to SOD1 Gene Mutation

3 1

What is this study about?

This clinical trial is focused on studying a condition known as Amyotrophic Lateral Sclerosis (ALS), which is associated with a specific genetic change called the SOD1 gene mutation. The study is investigating a treatment called BIIB067, also known as Tofersen. Tofersen is a solution that is injected into the spinal canal, a method known as intrathecal use. The purpose of the study is to evaluate how effective Tofersen is in adults who carry the SOD1 mutation but do not yet show symptoms of ALS.

The study will begin with a period where participants’ natural health progression is observed. After this, participants will be randomly assigned to receive either Tofersen or a placebo, which is a solution that looks like the treatment but does not contain the active substance. This part of the study will help researchers understand the effects of Tofersen compared to no active treatment. Participants will be monitored over time to see if they develop symptoms of ALS and to assess any changes in their health status.

Following the initial phase, there will be an open-label extension, where all participants will have the opportunity to receive Tofersen. Throughout the study, researchers will collect information on various health measures, including changes in physical abilities and breathing function. The study aims to provide valuable insights into the potential benefits of Tofersen for individuals at risk of developing ALS due to the SOD1 mutation.

1 joining the study

Upon joining the study, participation is confirmed for individuals who are clinically presymptomatic for amyotrophic lateral sclerosis (ALS) with a confirmed superoxide dismutase 1 (SOD1) mutation.

Eligibility is determined by specific criteria, including a rapidly progressive SOD1 mutation and plasma neurofilament light chain (NfL) levels below a certain threshold.

2 initial assessment

An initial assessment is conducted to establish baseline measurements. This includes evaluating functional abilities using the ALS Functional Rating Scale, which assesses respiratory, bulbar function, gross motor skills, and fine motor skills.

Baseline measurements of slow vital capacity (SVC) and plasma NfL concentrations are also taken.

3 treatment phase

Participants receive the study medication, BIIB067 (tofersen), administered as a solution for injection via intrathecal use. This involves injecting the medication into the space around the spinal cord.

The treatment phase is divided into several parts, with the primary objective of evaluating the efficacy of tofersen in delaying the onset of clinically manifest ALS.

4 monitoring and follow-up

Participants are monitored for the emergence of clinically manifest ALS over a period of up to 24 months from the baseline of Part B.

Secondary outcomes include changes in ALS functional scores, SVC, and plasma NfL concentrations, as well as the occurrence of adverse events and serious adverse events.

5 long-term evaluation

The study includes a long-term follow-up period, extending up to 5.6 years, to assess the time to emergence of clinically manifest ALS and other long-term outcomes.

Participants are evaluated for changes in cerebrospinal fluid (CSF) SOD1 concentrations and other health indicators.

6 completion of study

The study is estimated to conclude by October 18, 2027, with all data collected and analyzed to determine the efficacy and safety of tofersen in delaying the onset of ALS symptoms in presymptomatic individuals with a SOD1 mutation.

Who Can Join the Study?

Participants must have a specific type of genetic change called a SOD1 mutation. This mutation should be confirmed by a central reader or approved by a special committee.
Participants should have a plasma NfL level below a certain threshold. Plasma NfL is a substance in the blood that can indicate nerve cell damage.
Participants must not show any symptoms of ALS. This means they should not have any signs of the disease yet.
Participants can be of any gender.
Participants must be adults, which means they should be 18 years or older.
Other specific criteria defined in the study protocol may also apply.

Who Cannot Join the Study?

Individuals who do not have the specific genetic mutation related to Amyotrophic Lateral Sclerosis (ALS). This is a condition that affects nerve cells in the brain and spinal cord.
Individuals who are not carriers of the SOD1 gene mutation. This is a specific change in a gene that can be linked to ALS.
Individuals who do not have elevated levels of neurofilament (NF). Neurofilament is a type of protein found in nerve cells, and higher levels can indicate nerve damage.
Individuals who are not adults. The study is only for adults, which means people who are 18 years or older.
Individuals who already show symptoms of ALS. The study is for those who do not yet have symptoms.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Medizinische Hochschule Hannover	Hanover	Germany
Hospital Universitario Y Politecnico La Fe	Valencia	Spain

Other Sites

Site Name	City	Country
Norrlands University Hospital	Umea	Sweden
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Hopital Beaujon	Clichy	France
Neuroprotect Sp. z o.o.	Warsaw	Poland
Aedgvhn Omrdcpightc Unkmuuagzmfds Cduxpztckafv Duzfi Sjojkr E Dhkpy Slxmghi Di Trlsok	Turin	Italy

Trial status

Country	Status	Recruitment Start
France	Not recruiting	17.05.2021
Germany	Not recruiting	17.05.2021
Italy	Not recruiting	17.05.2021
Poland	Not recruiting	17.05.2021
Spain	Not recruiting	17.05.2021
Sweden	Not recruiting	17.05.2021

Trial locations

Investigated drugs:

Tofersen

Tofersen is a medication being studied for its effectiveness in adults who carry a specific genetic mutation known as superoxide dismutase 1 (SOD1). This mutation is linked to certain neurological conditions. The trial aims to see if tofersen can help these individuals before they show any symptoms. The study focuses on people with elevated levels of a protein called neurofilament, which can be a sign of nerve damage.

Investigated diseases:

Amyotrophic Lateral Sclerosis (ALS) associated with SOD1 gene mutation – This is a rare neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to the progressive loss of muscle control. It is specifically linked to mutations in the SOD1 gene, which can cause the abnormal accumulation of proteins that damage motor neurons. As the disease progresses, individuals may experience muscle weakness, twitching, and eventually, the inability to move, speak, swallow, or breathe independently. The progression of symptoms can vary, but it typically leads to significant physical disability over time. The condition is characterized by the gradual degeneration of motor neurons, which are responsible for transmitting signals from the brain to the muscles.

Trial ID:

2023-505641-12-00

Protocol code:

233AS303

NCT ID:

NCT04856982

Trial Phase:

Therapeutic confirmatory (Phase III)

Other Trials to Consider

#1 Clinical Trials Search in Europe

Study of Tofersen for Adults with Presymptomatic Amyotrophic Lateral Sclerosis (ALS) Due to SOD1 Gene Mutation

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?