This is an OLE study conducted to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical effects of WVE-004 in adult participants with ALS, FTD, or mixed ALS/FTD phenotype with a documented mutation in the C9orf72 gene. To participate in the study, participants must have successfully completed Phase 1b/2a WVE-004-001 study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Eligible participants successfully completed the Phase 1b/2a WVE-004-001 study, met all inclusion criteria, and none of the exclusion criteria. Participants were administered 10 mg of WVE-004 by intrathecal (IT) injection once every 12 weeks (Q12W) for 96 weeks.
Erasmus MC
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands
University of Oxford - Nuffield Department of Clinical Neurosciences
Oxford, United Kingdom
Number of Occurrences of Participants With Adverse Events (AEs) Severe AEs, Serious Adverse Events (SAEs), and Withdrawals Due to AEs
A treatment-emergent adverse event (TEAE) is defined as any event not present before exposure to study treatment or any event already present that worsens in either intensity or frequency after exposure to study treatment.
Time frame: Day 1 to Week 24 (early termination cutoff)
Change From Baseline in Clinical Dementia Rating Plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration (CDR Plus NACC FTLD)
Disease progression was measured using the CDR plus NACC FTLD scale. The evaluation included assessments of both cognitive and functional measures, including memory, orientation, judgment and problem-solving, involvement in community affairs, home and hobbies, personal care, language and behavior, and comportment and personality. The rating for each domain was scored using a scale of 0 (none) to 3 (severe) based on the participant's function in relation to cognitive ability (not impairment due to other factors) and past performance (or baseline level of functioning). The overall rating for each domain was summed to provide a global clinical measure of the disease. The CDR plus NACC FTLD score ranges from 0 to 24, with a higher score indicating more severe impairment.
Time frame: Day 1 to Week 120 (end of study)
Change From Baseline in ALS Functional Rating Scale-Revised (ALSFRS-R)
ALSFRS-R is an instrument to monitor the function of participants with ALS and their disease progression. The components of the scale are grouped into 4 factors or domains that encompass gross motor tasks, fine motor tasks, bulbar functions, and respiratory functions. These components measure speech, salivation, swallowing, writing, feeding, dressing, turning, walking, climbing, breathing, dyspnea, orthopnea, and respiratory insufficiency. Each component is scaled from 0 to 4, with 4 being normal, and a total score is calculated
Time frame: Day 1 to Week 120 (end of study)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Change From Baseline in Handheld Dynamometry (HHD)
Handheld dynamometry was used to provide an objective quantitative measurement of strength, a key hallmark of decline in ALS disease progression. For the HHD assessment, participants would be sitting in a hard-backed chair with armrests or a wheelchair. Muscle strength was tested using the HHD device. Measurements were recorded in pounds. A value of 0 was assigned to a given muscle if a participant could not assume the testing position due to weakness.
Time frame: Day 1 to Week 120 (end of study)
Change From Baseline in Pulmonary Function Testing (Forced Vital Capacity (FVC))
Pulmonary function tests (PFTs) are tests that show how well your lungs are working. The tests measure lung volume, capacity, rates of flow, and gas exchange.
Time frame: Day 1 to Week 120 (end of study)
Change From Baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ)-5
The ALSAQ-5 is specifically used to provide a brief assessment of the impacts of ALS on participants. Participants were asked to think about the difficulties they have experienced during the reporting period and scale each event as never/rarely/sometimes/often/always or cannot do at all.
Time frame: Day 1 to Week 120 (end of study)
Change From Baseline in the Concentration of Poly-glycine-proline (Poly-GP) Levels in the Cerebrospinal Fluid (CSF)
CSF samples were collected to determine the concentration of poly-GP levels in CSF.
Time frame: From Baseline to Week 12