Given the lack of treatment options for amyotrophic lateral sclerosis (ALS) on the market, many people with the disease turn to clinical trials to try investigational treatments. However, finding, choosing, and enrolling in a clinical trial can be a challenging process. Here, we’ve gathered information about the phase 3 trials currently recruiting participants with sites in the United States as of April 2022.
Phase 3 trials represent treatments that have already undergone testing for dosing, safety, and sometimes efficacy, and are the largest clinical trials conducted before a drug is submitted to the FDA for approval. Of course, there are many other promising investigational treatments undergoing phase 1 and 2 clinical trials. You can read more about the different trial phases here. For comprehensive information about all ALS trials currently active and/or recruiting, including phase 1 and 2 trials as well as international phase 3 trials, visit our clinical trials database.
Phase 3 Trials Currently Recruiting in the US:
Edaravone, sold under the brand names Radicava and Radicut, is one of two FDA approved treatments for the management of ALS disease progression. It is, however, currently available only as an intravenous infusion, which received FDA approval in 2017. This trial is testing a new oral formulation of the drug. While this current trial is still ongoing, the FDA accepted a New Drug Application for Oral Edaravone in January 2022.
Oral Edaravone Quick facts:
Sponsor: Mitsubishi Tanabe Pharma Development America, Inc
Duration: 48 weeks
Trial: Participants will receive one of two doses of oral edaravone. Upon completion of the clinical trial, participants may enroll in a separate open label extension study to continue treatment.
Size: 380 participants
Mechanism of Action: Edaravone can act as a “free radical scavenger,” meaning it can protect cells from the effects of unstable molecules that cause oxidative stress. It may also reduce the inflammation caused by microglial cells – immune cells found in the central nervous system. While the exact mechanism of action in ALS is unknown, it is believed it is a combination of these two effects.
For more info about Oral Edaravone, click here.
Masitinib is an investigational treatment that inhibits certain proteins in mast cells and macrophages, immune cells that may play roles in neuroinflammation and neurodegeneration. This study seeks to confirm the results from a previous phase 2b/3 trial that indicated a survival benefit.
Masitinib Quick Facts:
Sponsor: AB Science
Duration: 48 weeks
Trial: Participants may receive one of two different doses of masitinib or placebo.
Size: 495 participants
Mechanism of action: Masitinib is a tyrosine kinase inhibitor, also targeting the CSF-1R and c-Kit pathways that are active in certain immune cells and are linked with inflammation. Studies in animals, as well as previous clinical trials in ALS, Multiple Sclerosis, and Alzheimer’s disease have shown that inhibiting these pathways may protect against neuroinflammation and neurodegeneration.
For more info about Masitinib, click here.
BIIB067, also known as Tofersen, is an experimental antisense oligonucleotide (ASO) treatment for genetic ALS caused by mutations in the SOD1 gene. This trial seeks to test its effectiveness in people who carry this mutation, but have not yet developed ALS symptoms. A phase 3 trial of Tofersen in symptomatic people with ALS was completed in 2021, and did not meet its primary endpoint, but did meet multiple secondary and exploratory endpoints.
Tofersen Quick Facts:
Trial: This is a multi-part trial in which participants who carry specific SOD1 gene variants but are asymptomatic for ALS will receive monthly blood draws that will monitor neurofilament light chain (NfL), a biomarker of neurodegeneration. An increase in NfL over a specific threshold may be followed by dosing with Tofersen, an experimental ASO treatment for SOD1 ALS.
Size: 150 participants
Mechanism of action: Tofersen is an ASO, a small molecule of DNA that can enter a cell and bind with mRNA strands, effectively “turning down” a gene and disrupting the production of specific proteins. Tofersen binds to SOD1 mRNA, reducing the production of the SOD1 protein, which may be protective against SOD1 ALS.
For more information about BIIB067, click here.
Reldesemtiv is a “fast skeletal muscle troponin activator” that may help relieve muscle weakness and wasting caused by ALS and other neurodegenerative diseases. While a phase 2 trial did not meet its primary or secondary endpoints, a post-hoc analysis of the trial data demonstrated that participants who received the active drug declined less than those in the placebo group.
Reldesemtiv Quick Facts:
Duration: 50 weeks
Trial structure: This trial begins with a screening period of up to 14 days, followed by 2:1 randomization so that 66% of participants will receive active treatment and 33% will receive placebo for 24 weeks. This will be followed by an additional 24 weeks of an open label period, with no placebo, and two different doses of Reldesemtiv.
Size: 555 participants
Mechanism of action: Sarcomeres are basic structures in muscle fibers that allow the muscle to contract in response to signals from the nervous system. They rely on the release of calcium in the muscles to function. Reldesemtiv is a fast skeletal muscle troponin activator, a compound that helps these sarcomeres respond more readily to signals from the brain by increasing their sensitivity to calcium. This may help muscle resist atrophy and wasting, despite decreasing signals from the nervous system due to ALS.
For more information about Reldesemtiv, click here.
AMX0035 is a combination of two compounds – sodium phenylbutyrate (PB), a compound that is FDA approved for another indication, and tauroursodeoxycholic acid (TURSO), a bile salt available as a supplement, but also approved for another indication in countries outside the USA. Research has shown they may work together to block certain cellular pathways linked to neuronal death from ALS. A phase 2 trial met its primary endpoint and continued monitoring of participants on the open label extension for this trial demonstrated promising survival benefits. Canada has accepted a New Drug Submission for AMX0035. Amylyx has also submitted a New Drug Application in the United States, as well as a Marketing Authorization Application in Europe.
AMX0035 Quick Facts:
Sponsor: Amylyx Pharmaceuticals
Duration: 48 weeks
Trial: Participants will be randomized in a 3:2 ratio so that 60% will receive active treatment and 40% will receive placebo.
Mechanism of Action: AMX0035 is a combination therapy made up of PB and TURSO designed to reduce neuronal death through blockade of key cellular death pathways originating in the mitochondria and endoplasmic reticulum (ER). Mitochondria provide energy for cells, while the ER is involved in producing and managing proteins. The current proposed mechanism of action is that TURSO may help support mitochondrial health, while PB may help reduce the toxic clumping of proteins.
For more information about AMX0035, click here.
MN-166 (Ibudilast) is a small molecule drug that inhibits several enzymes involved in the inflammatory process. A phase 2 trial demonstrated that it may be effective in treating ALS in combination with riluzole, especially when given to people less than 18 months out from the onset of their first symptoms.
Ibudilast Quick Facts:
Duration: 12 months
Trial Structure: The study will consist of a screening phase of up to 30 days. Following the screening phase, participants will be randomized so that 50% receive MN-166 and 50% receive placebo. Upon completion of the double-blind phase, participants may continue active treatment on open label extension for six months.
Mechanism of action: Ibudilast promotes neuroprotection by inhibiting inflammatory cytokines, macrophage migration inhibitory factor, and phosphodiesterases. It is also thought to reduce inflammation by inhibiting glial activation and to increase autophagy or cleanup of misfolded proteins.
For more information about Ibudilast, click here.
ION363 is an antisense oligonucleotide (ASO) experimental treatment for people with ALS caused by a mutation in the FUS gene.
ION363 Quick Facts:
Sponsor: IONIS Pharmaceuticals
Duration: 29 weeks of randomized placebo controlled period followed by 77 weeks of open label treatment
Trial: Participants are randomized in a 2:1 ratio so that 66% will receive active treatment and 33% will receive placebo for a period of 29 weeks. This will be followed by an open label period, with no placebo, for 77 weeks.
Size: 64 participants
Mechanism of action: ION363 is an ASO, a small molecule of DNA that can enter a cell and bind with mRNA strands, effectively “turning down” a gene and disrupting the production of specific proteins. ION363 binds to FUS mRNA, reducing the production of the FUS protein, which may be protective against FUS ALS.
For more information about ION363, click here.
SLS-005, also known as trehalose, is a naturally occurring disaccharide, a kind of sugar molecule, that may prevent certain pathological processes in cells. This trial will begin recruiting by the end of January 2022 as the fifth regimen in the Healey Platform Trial, in which several investigational therapies are tested simultaneously while sharing a placebo group.
SLS-005 Quick Facts:
Sponsor: Seelos Therapeutics
Duration: 6 months, with options to continue open label extension or rerandomize into the trial again.
Trial: Participants will be randomized in a 3:1 ratio, with 75% receiving active treatment and 25% receiving placebo. After completion of the placebo controlled portion, participants can choose to rerandomize within the trial again or continue on to receive active treatment on an open label extension.
Size: 160 participants
Mechanism of action: Trehalose is a naturally occurring sugar molecule that may promote autophagy, or the process through which cells break down, expel, or recycle old proteins and other materials they may no longer need. Preclinical studies have shown that trehalose reduces the amount of SOD1 and TDP43 proteins in motor neurons in animal models of ALS while delaying disease progression.
To learn more about SLS-005, click here.
What to do next:
- If you’re interested in participating in one of these trials, consult your doctor and reach out to the trial sponsor for more information.
- To learn more about how the ALS Therapy Development Institute (ALS TDI) is working to provide fuel for the clinical trial pipeline as the Drug Discovery Engine for ALS, click here.
- To learn about other trials, including international trials and Phase 1 and 2 trials, visit ALS TDI’s clinical trials database.