Despite robust, sustained reductions in poly(GP), no clinical benefit was seen at 24 weeks, and reductions in poly(GP) were not associated with stabilization in functional outcomes. Based on these data, Wave decided to stop development of WVE-004.

This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of intrathecal (IT) WVE-004 in adult patients with C9orf72-associated ALS or FTD. To participate in the study, patients must have a documented mutation (GGGGCC [G4C2] repeat expansion) in the first intronic region of the C9orf72 gene and be diagnosed with ALS or FTD.

Inclusion Criteria:

1. ALS-specific: Diagnosis of ALS based on clinical manifestations.
2. ALS-specific: Clinically diagnosed possible, laboratory supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology revised El Escorial criteria.
3. ALS-specific: Patients receiving riluzole have been on a stable dose for a minimum of 30 days.
4. ALS-specific: Patients on edaravone have received a minimum of 1 cycle (28 days).
5. ALS-specific: Patients discontinuing riluzole or edaravone had the last dose administered ≥1 month prior to Screening.
6. FTD-specific: Must have Global Clinical Dementia Rating - Frontotemporal Lobar Degeneration (CDR® plus NACC FTLD) score of 0.5 or 1.
7. FTD-specific: Able to undergo periodic magnetic resonance imaging (MRI) of the brain. Participants with mixed phenotype (ALS and FTD) need not undergo MRI if their ALS symptoms prevent it.
8. Mixed-phenotype: Patients who are mixed phenotype (ALS and FTD) must meet both the ALS-specific and FTD-specific criteria.

Exclusion Criteria:

1. Clinically significant medical finding on the physical examination other than C9orf72-associated ALS or FTD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the trial procedures
2. Received any other investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Received an investigational oligonucleotide, within the past 6 months or 5 half-lives of the drug, whichever is longer.