Due to the specificity of this treatment, this clinical trial is only open to individuals with a variant (mutation) in the SOD1 gene.
Variants (mutations) in a gene called Superoxide dismutase 1 (SOD1) are known to contribute to ALS onset and disease progression. The gene is believed to gain a toxic function that is damaging to the nerve cells that control voluntary muscles, called motor neurons. The experimental therapeutic ALN-SOD is an RNA interference therapeutic, which is a class of drugs that can silence genes. By silencing the abnormal SOD1 gene in people living with SOD1-ALS, researchers theorize this can slow down or stop disease progression.
This Phase 1 study will recruit 42 participants, who will be randomly assigned to receive either different doses of the experimental therapeutic ALN-SOD, or placebo by intrathecal (IT) injection. After four weeks, the study will have an extension period where all participants will receive ALN-SOD. The study will evaluate the safety and effectiveness of ALN-SOD by measuring adverse events, biomarker measures, and concentration of the drug and presence of antibodies against the drug over time. The presence of antibodies could make the drug less effective or lead to side effects.
Antibodies are proteins that are produced by the immune system to protect the body against foreign invaders like bacteria and viruses, and work by binding to specific proteins on the harmful agents and triggering their removal and/or destruction. In this Phase 2 clinical trial, researchers will be testing the safety of a human antibody (called AP-101) designed to target an ALS-linked protein called SOD1. Evidence suggests that the misfolding of SOD1 in cells can cause the protein to take on a toxic gain of function. Researchers are hopeful that targeting this protein may represent a promising strategy for the treatment of ALS. A previous Phase 1 study found the drug to be safe and well-tolerated at the tested doses. In this follow-up study, researchers expect to enroll 63 participants who will be randomly divided to either receive the active drug (AP-101) or placebo intravenously (IV), for 48 weeks. Both individuals with familial, SOD1-ALS and sporadic disease will be eligible to participate. Researchers will monitor participants to ensure that the drug is safe, identify any side effects, determine the appropriate dosage, and learn more about how the body breaks down the drug internally.