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 March 2023.
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:
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.
tBIIB067, also known as tofersen and Qalsody, is an 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. In April 2023, tofersen received FDA approval for treating people with symptomatic SOD1-related ALS.
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.
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.
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.