ALS, FTD
Conditions
Brief summary
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.
Interventions
DRUGWVE-004
WVE-004 is a stereopure antisense oligonucleotide (ASO)
DRUGPlacebo
Artificial cerebrospinal fluid (aCSF)
Sponsors
Wave Life Sciences Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Proportion of patients with adverse events (AEs) | Period 1 Day 1 to Period 2 Week 24 (end of study) |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF) | Period 1 Day 1 to Period 2 Week 24 (end of study) |
| Pharmacodynamic: Change from baseline in concentration of poly-GP levels in the CSF | Period 1 Day 1 to Period 2 Week 24 (end of study) |
Countries
Australia, Belgium, Canada, Ireland, Netherlands, New Zealand, Sweden, United Kingdom
Outcome results
None listed