Action: Inhibition of complement, which is involved in inflammation. It was used to treat adult patients with paroxysmal nocturnal hemoglobinuria (PNH).
Clinical Trial Status: Phase II
Participants are being recruited.
Action: Inhibition of C3 complement, which is involved in inflammation of the motor endplates at the nerve junction. It is used to treat adult patients with paroxysmal nocturnal hemoglobinuria (PNH). Animal studies have been inconclusive regarding the efficacy of complement inhibition. (Lobsiger et al., 2013; Woodruff et al., 2008)
Clinical trial status: Evaluation of the efficacy and safety of Pegcetacoplan (pegetacoplan) in adult patients Phase II
ClinicalTrials.gov Identifier: NCT04579666 not recruiting
Criteria for selection: Sporadic ALS with onset within 16.5 months (72 weeks) and slow vital capacity >60% of the predicted value
Dosage: Subcutaneous injection twice a week
Side effects: Streptococcus pneumoniae, meningococcus, and Haemophilus influenzae type B (vaccination required)
Note: Labulizumab (Yurtomiris®), an inhibitor of the C5 complement, was discontinued early after an interim analysis of a phase III trial, because it failed to demonstrate efficacy.
Recombinant human HGF protein
Action: Neurotrophic factor. It inhibits progression in rodent models (Ishigaki et al., 2007)
Clinical trial status: A phase II trial consisting of a placebo-controlled double-blind and open-label continuation study to evaluate the efficacy and safety of 6-month intraspinal administration of HGF protein (KP-100IT) using NP022 (intrathecal catheter and subcutaneous implant port). ALS severity of 1 or %FVC ≥70% within 30 months of onset
UMIN Study ID: UMIN000022050
End of entry: The observation date for the last case was completed.
AT-1501 (anti-CD40L) (Tegoprubar)
Action: Suppresses neuroinflammation
Clinical Trial Status: Phase IIa suppressed disease progression compared to that in the controls in the ALS clinical trial data.
Action: Suppresses neuroinflammation by inhibiting the interaction between CD40 ligand (CD40L), a surface antigen of immune cells, and CD40 receptors.
Clinical trial status: Phase IIa completed
Tegoprubart well tolerated, no serious adverse events.
ALSFRS decline was suppressed compared to that in the controls in an ALS clinical trial data set in the ALS PRO-ACT database*.
Dosage: Biweekly intravenous administration
Latozinemab, AL001, GSK4527223
Action: Recombinant human anti-sortilin monoclonal IgG1.
Sortilin is a sorting receptor for intracellular trafficking. It is involved in neurotrophic factors, signal transduction, and lysosomal degradation. It regulates the endocytosis and degradation of progranulin, a major cause of frontotemporal dementia. Progranulin levels are reduced by 50%-70% in this disease. Suppression of sortilin with this drug increases progranulin.
Clinical Trial Status: Phase 2 for ALS due to C9ORF72 mutation
The primary endpoints are safety, tolerability, pharmacokinetics and pharmacodynamics; plasma and CSF progranulin levels
ClinicalTrials.gov Identifier: NCT04436510
Action:Low dose (ld) IL2 boosted peripheral regulatory T cells (Tregs) and modified inflammation.
Clinical Trial Status: Phase II, completed
ClinicalTrials.gov Identifier: NCT02059759
Criteria for selection: ALS disease duration 24 months, VC 70%, not previously treated with riluzole.
Dosage: Subcutaneous injection in 5-day cycles every 28 days
Results: The primary efficacy outcome was time to death (survival) at 21 months (640 days) post-randomization. Aldesleukin tended to improve survival rates by 19% compared with a placebo, but the findings failed to reach statistical significance. In patients with lower levels of CSF phosphorylated neurofilament heavy chain (biomarker of disease severity), Aldesleukin results in a significant reduction – by 43% – in the risk of death and also slower disease progression in ALSFRS-R scores.