Clinical trial NCT04931862: Study of WVE-004 in Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-004 Administered Intrathecally to Patients With C9orf72-associated Amyotrophic Lateral Sclerosis (ALS) or Frontotemporal Dementia (FTD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: ALS
FTD
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-18
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Safety: Proportion of patients with adverse events (AEs)
timeFrame: Period 1 Day 1 to Period 2 Week 24 (end of study)
Secondary outcomes:
measure: Pharmacokinetic: Concentration of WVE-004 in cerebrospinal fluid (CSF)
timeFrame: Period 1 Day 1 to Period 2 Week 24 (end of study)
measure: Pharmacodynamic: Change from baseline in concentration of poly-GP levels in the CSF
timeFrame: Period 1 Day 1 to Period 2 Week 24 (end of study)
Other outcomes:
Locations:
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: Brisbane
country: Australia
facility: The Wesley Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Perron Institute
state: Western Australia
city: Leuven
country: Belgium
facility: UZ Leuven
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center - Research Institute
state: Quebec
city: Dublin
country: Ireland
facility: St James Hospital - Ireland
city: Rotterdam
country: Netherlands
facility: Erasmus University MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: New Zealand Brain Research Institute
city: Solna
country: Sweden
facility: Karolinska University Hospital
city: Cambridge
country: United Kingdom
facility: University of Cambridge
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Oxford
country: United Kingdom
facility: University of Oxford - Nuffield Department of Clinical Neurosciences
city: Sheffield
country: United Kingdom
facility: University of Sheffield
Study officials:
affiliation: Wave Life Sciences
name: Medical Director, MD
role: STUDY_DIRECTOR
References: